Idiopathic hypertrophic pachymeningitis mimicking prolactinoma with recurrent vision loss

Hong Kong Med J 2015 Aug;21(4):360–2
DOI: 10.12809/hkmj144295
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Idiopathic hypertrophic pachymeningitis mimicking prolactinoma with recurrent vision loss
Julie YC Lok, MRCSEd; Nelson KF Yip, FCOphth; Kelvin KL Chong, FCOphth; CL Li, FCOphth; Alvin L Young, FCOphth
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Corresponding author: Dr Alvin L Young (youngla@ha.org.hk)
 
 Full paper in PDF
 
Abstract
Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater, which may cause a compressive effect or vascular compromise. We report on a 28-year-old Chinese woman with a history of granulomatous mastitis 7 years previously and oligomenorrhoea, headache, blurred vision, and raised prolactin level 2 years previously, that was diagnosed as prolactinoma and treated conservatively with bromocriptine. However, she had recurrent bilateral vision loss when the bromocriptine was stopped. Her symptoms were resolved by high-dose steroid injection but remained steroid-dependent. Serial magnetic resonance imaging scan showed progressive diffuse thickening of the pachymeningitis with disappearance of pituitary apoplexy. Lumbar puncture showed lymphocytosis with no organisms. Open biopsy of the meninges was performed and histology showed features of inflammatory infiltrates and vasculitis. This is an unusual presentation of a rare condition in this age-group, with co-existing granulomatous mastitis and chronic otitis media, and is a diagnostic challenge mimicking pituitary macroadenoma and meningioma in initial magnetic resonance imaging scans.
 
 
[Abstract in Chinese]
 
Introduction
Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition characterised by fibrosis and thickening of the dura mater. Diagnosis of idiopathic hypertrophic pachymeningitis requires a high index of suspicion, as its initial manifestation could be subtle clinically and radiologically. Idiopathic hypertrophic pachymeningitis has posed considerable diagnostic challenges to attending clinicians, including radiologists, neurologists, and ophthalmologists because of its highly variable presentation. Apart from clinical subtlety and variability, idiopathic hypertrophic pachymeningitis is also a great imposter because it can mimic other common and important neurological conditions such as prolactinoma.
 
Case report
A 28-year-old Chinese woman with a history of granulomatous mastitis 7 years previously was noted to have oligomenorrhoea, nausea, headache, and raised prolactin level of 1261.0 mIU/L (reference range [RR], 108.8-557.1 mIU/L) since March 2011. Her baseline hormone profile was otherwise normal. Plain magnetic resonance imaging (MRI) scan showed an enlarged pituitary gland of up to 1.6 cm (Figs 1a and 1b). At that time she was diagnosed with prolactinoma and treated with bromocriptine; her prolactin level was well-controlled subsequently.
 

Figure 1. Magnetic resonance images showing generalised increased pachymeningeal enhancement in the bilateral frontal-parietal-temporal regions just before steroid treatment in June 2013
Non-contrast (a) coronal and (b) sagittal scans showing an enlarged pituitary gland of up to 1.6 cm with optic compression and central necrosis (arrows); contrast (c) coronal and (d) sagittal scans showing diffuse pachymeningeal thickening and enhancement over cavernous sinus, clivus, skull base extended into orbit (arrows)
 
After cessation of bromocriptine at the end of 2012, she developed periodic headache and flickering vision loss since May 2013. Her best-corrected visual acuities were 20/40 and 20/30 in her right and left eyes, respectively. She developed red colour desaturation of around 30%. Humphrey visual field 30-2 test showed superior field loss in the right eye, while the left eye was full field loss. Six weeks later her visual acuity decreased to 20/800 in the right eye and 20/400 in the left eye. She was given dexamethasone and her visual acuity increased to 20/20 and 20/16 in the right and left eyes, respectively. Other slit-lamp and fundal examinations were unremarkable. There was no papilloedema. There was no involvement of other cranial nerves. Glasgow Coma Scale Score was 15/15 throughout. Magnetic resonance imaging with contrast showed increased contrast enhancement and inflammation over the dura of the sella and cavernous sinus (Figs 1c and 1d). Her symptoms resolved and visual function recovered quickly with high-dose steroid. However, she developed steroid dependency since repeated attacks developed when the steroid was stopped.
 
Serial MRI scan showed progressive diffuse thickening of the pachymeningitis with disappearance of pituitary apoplexy, together with chronic otitis media (Figs 1c and 1d). Lumbar puncture showed 13 cm H2O and lymphocytosis without organisms. Open biopsy of the meninges was performed and histology showed features of inflammatory infiltrates and vasculitis, but was negative for malignancy (Fig 2). Gene rearrangement polymerase chain reaction assay for immunoglobulin (Ig) heavy chain, T-cell receptor (TCR)–beta and TCR-gamma all showed no clonal peak. Polymerase chain reaction for Mycobacterium tuberculosis and culture for dural biopsy were also negative; IgG4 was 975 mg/L (RR, 61-1214 mg/L). Complete blood count showed normal haemoglobin, white blood cell, and platelet levels. Liver and renal function tests, serum calcium, creatine kinase, and lactate dehydrogenase levels were normal. Erythrocyte sedimentation rate was raised to 113 mm/h (RR, 0-20 mm/h). C-reactive protein was raised at 67.4 mg/L (reference level, <9.9 mg/L). In coagulation profile, activated partial thromboplastin time was slightly prolonged to 40.0 seconds (RR, 28.2-37.4 seconds). Autoimmune markers, including anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-DNA immunofluorescence test, anti-extractable nuclear antigen, anti-cardiolipin antibodies, and rheumatoid factors are all negative except for the presence of lupus anticoagulant. Complement C3 was normal while complement C4 was slightly raised to 0.42 g/L (RR, 0.1-0.4 g/L). Serum vitamin B12 level was 552 pmol/L (RR, 156-698 pmol/L) and serum folate level was 29.3 nmol/L (RR, 10.4-42.4 nmol/L); IgG4 was 975 mg/L. Virology screening—including human immunodeficiency virus, hepatitis B virus, and hepatitis C virus—was negative. Serum and cerebrospinal fluid Venereal Disease Research Laboratory tests were negative. Chest X-ray was clear with no features of tuberculosis or sarcoidosis.
 

Figure 2. Histology slide showing inflammatory changes as vasculitis (arrows) and negative for malignancy (H&E; original magnification, x 10)
 
The patient was initially treated with pulse steroid and was well-controlled by low-dose steroid. She remained symptom-free 6 months after biopsy.
 
Discussion
Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition involving focal and/or diffuse thickening and fibrosis of the dura mater. Thickened dura mater with local mass effect may be pathognomonic of this condition. This pressure effect may serve as a mechanistic explanation of the observed neurological defect. As almost every part of the dura mater can be affected focally and/or diffusely, there is a highly variable clinical picture.1 2 Diagnosis is almost always made by exclusion of a large number of aetiologies, for example, infectious causes such as Lyme disease, syphilis, and M tuberculosis; inflammatory causes such as Wegener granulomatosis,3 rheumatoid arthritis, Behçet disease, and sarcoidosis (which is rare in Chinese people); and malignancy. In this patient, these tests were all negative, so the diagnosis of idiopathic hypertrophic pachymeningitis was made.
 
Demographically, the median age of patients with idiopathic hypertrophic pachymeningitis is 58.3 years (standard deviation, 15.8; range, 37-88 years).4 5 6 Only a few paediatric patients have been reported, with the youngest age being 2 years and 11 months in India.7 Our patient had early-onset disease. There are few data on ethnicity due to the rarity of the disease. Idiopathic hypertrophic pachymeningitis is extremely rare in Chinese people.
 
The exact aetiopathophysiology of idiopathic hypertrophic pachymeningitis is not known. It is believed to be autoimmune in origin.8 Lupus anticoagulant is a type of autoantibody that binds to phospholipid and protein, which is commonly associated with autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome.9 Our patient’s symptoms and signs did not fit into any diagnostic category of autoimmune disease. Only the presence of lupus coagulants might suggest that idiopathic hypertrophic pachymeningitis is a form of vasculitis, which might share some common phenomenon with other autoimmune diseases, although the true relationship is controversial.
 
Clinically, headache is by far the most common feature and the optic nerve is one of the most common cranial nerves to be involved, which was the case for this patient. Multiple cranial nerve involvement, ataxia, cortical blindness, psychosis, motor function disturbance, fever, convulsion, and/or loss of consciousness have all been reported.5 6 Yamada et al2 thought that the inflammatory thickening of the dura may cause damage to the superior hypophyseal artery resulting in subarachnoid haemorrhage and apoplexy in the anterior lobe of the pituitary gland. The posterior lobe was spared in their patient, who had a normal hormonal profile, unlike our patient. The initial enlarged pituitary gland with raised prolactin was more likely to result from the stalk effect than from true prolactinoma.
 
Granulomatous mastitis is a rare idiopathic chronic benign breast condition, which is believed to be autoimmune in origin, and mainly affects women of child-bearing age.10 Granulomatous mastitis is mainly diagnosed by exclusion of other diagnoses. To the best of our knowledge, this is the first case of idiopathic hypertrophic pachymeningitis reported with the association of granulomatous mastitis, possibly related to the scarcity of cases affecting menstruating women.
 
Idiopathic hypertrophic pachymeningitis is a rare condition with a highly variable clinical presentation making accurate and timely diagnosis difficult. Therefore the attending clinician should maintain high vigilance in the event of an atypical presentation of a presumably typical disease. Early diagnosis and prompt therapeutic intervention such as high-dose steroid may be the key to preserving vision as well as life.
 
References
1. Christakis PG, Machado DG, Fattahi P. Idiopathic hypertrophic pachymeningitis mimicking neurosarcoidosis. Clin Neurol Neurosurg 2012;114:176-8. Crossref
2. Yamada SM, Aoki M, Nakane M, Nakayama H. A case of subarachnoid hemorrhage with pituitary apoplexy caused by idiopathic hypertrophic pachymeningitis. Neurol Sci 2011;32:455-9. Crossref
3. Yokoseki A, Saji E, Arakawa M, et al. Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody. Brain 2014;137:520-36. Crossref
4. Yonekawa T, Murai H, Utsuki S, et al. A nationwide survey of hypertrophic pachymeningitis in Japan. J Neurol Neurosurg Psychiatry 2014;85:732-9. Crossref
5. Riku S, Kato S. Idiopathic hypertrophic pachymeningitis. Neuropathology 2003;23:335-44. Crossref
6. Kupersmith MJ, Martin V, Heller G, Shah A, Mitnick HJ. Idiopathic hypertrophic pachymeningitis. Neurology 2004;62:686-94. Crossref
7. Sharma PK, Saikia B, Sharma R, Gagneja V, Khilnani P. Pachymeningitis in a young child responded to antitubercular therapy: a case report. J Child Neurol 2014;29:NP92-5. Crossref
8. Masson C, Boukriche Y, Colombani JM. Inflammatory hypertrophic cranial pachymeningitis. Presse Med 2001;95:65-70.
9. Favaloro EJ, Wong RC. Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines. Pathology 2014;46:481-95. Crossref
10. Poovamma CU, Pais VA, Dolas SC, Prema M, Khandelwal R, Nisheena R. Idiopathic granulomatous mastitis: a rare entity with a variable presentation. Breast Dis 2014;34:101-4.

Peritoneal implantation of ureter in cadaveric renal transplant

Hong Kong Med J 2015 Jun;21(3):269–71
DOI: 10.12809/hkmj134171
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Peritoneal implantation of ureter in cadaveric renal transplant
CF Tsang, MB, BS, MHKIBSC1; WK Ma, FRCS, FHKAM (Surgery)2; FK Cheung, FRCS, FHKAM (Surgery)1
1 Urology Division, Department of Surgery, Princess Margaret Hospital, Laichikok, Hong Kong
2 Urology Division, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong
Corresponding author: Dr WK Ma (kitkitma@yahoo.com)
 
 Full paper in PDF
Abstract
We report here a case of complication of peritoneal implantation of ureter in cadaveric renal transplant. The patient presented with anuria and delayed graft function. The diagnosis was suspected upon physical examination and radiological investigation. The complication was managed with reimplantation of the ureter into the bladder and the patient recovered with good graft function. We discuss this case, review the literature on this rare complication, and share our suggestions on how it can be prevented.
 
 
[Abstract in Chinese]
 
Introduction
Oliguria or anuria early after cadaveric renal transplant (CRT) is not uncommon and can be related to numerous causes. We report here a rare case of complication of ureteric implantation in the peritoneum in CRT causing anuria. Diagnosis was suspected early on day 1 after operation by clinical examination and abdominal X-ray (AXR), and confirmed with non-contrast computed tomography (CT) of the abdomen and pelvis. The complication was managed with immediate reimplantation of the ureter into the bladder and the patient had an uneventful recovery thereafter with good graft function. To our knowledge, this is the first reported case in Hong Kong and the fifth in the world. We believe the actual incidence is underreported and would like to share our suggestions on how to avoid this rare complication.
 
Case report
A 29-year-old man with Alport’s syndrome developed end-stage renal failure in 2009 and was started on intermittent peritoneal dialysis in 2011. His serum creatinine level and estimated glomerular filtration rate were 1458 µmol/L and 5.1 mL/min, respectively. In September 2013, he received CRT from a 60-year-old man with brain stem death due to haemorrhagic stroke. The donor’s serum creatinine was 88 µmol/L and there were no hypotensive episodes or inotrope infusion before organ harvesting.
 
The cadaveric right kidney was transplanted into the right iliac fossa of the recipient, with good perfusion and turgor after release of vascular clamps. No urine was noted at cut-end of the graft ureter at the time of implantation. A needle test to aspirate pre-filled gentamicin solution from the bladder was done and extravesical ureteroneocystostomy with Lich-Gregoir technique was performed with a 7-French, 15-cm long, double J ureteric stent in situ. The total operating time was 2 hours and 20 minutes; with cold ischaemic time of 7 hours 41 minutes and second warm ischaemic time of 33 minutes. The patient was haemodynamically stable but remained anuric 12 hours after operation with a serum creatinine level of 1268 µmol/L. An urgent Doppler ultrasound of the graft kidney was done and showed good perfusion of graft with patent renal artery and vein. Repeated physical examination revealed a slightly distended abdomen and AXR showed the distal coil of double J stent above the pelvis level (Fig a), leading to the suspicion of implantation of the ureter into the peritoneum. Subsequent non-contrast CT of the abdomen and pelvis confirmed placement of the ureteric stent outside the bladder (Fig b and c).
 

Figure. Kidney ureter bladder: (a) X-ray showing distal coil of ureteric stent above the pelvis level (arrow); (b) computed tomography (CT) with coronal reconstruction showing position of the ureteric stent (arrow), and (c) CT scan showing tip of the ureteric stent outside the bladder (arrow)
 
Exploration and reimplantation of ureter were performed immediately. It was noted that the ureter was implanted into the thickened peritoneum at a level just above the right upper lateral bladder wall, with urine draining into the intra-abdominal cavity. The detrusor layer was thin and not well developed. The anastomosis was taken down and ureteroneocystostomy was refashioned with the same Lich-Gregoir technique. There was immediate return of good urine output and his serum creatinine levels improved to 186 µmol/L and 126 µmol/L on postoperative day 3 and week 4, respectively.
 
Discussion
Post–renal transplant urological complications are not uncommon. Commonly reported complications include thromboembolic events of vascular anastomosis, acute tubular necrosis, lymph leak, and urinary reflux. Recent retrospective series have reported incidence rates of 2.8% to 15.5% of urological complications after CRT.1 2 3 These are significantly decreased rates compared with those in an earlier series after introduction of various modified techniques of implantation and use of ureteric stents.1 Peritoneal implantation of ureter constitutes an incidence of 0.1% to 0.2% only.3 4 Gibbons et al4 reported a case of ureteric implantation into an ovarian cyst in addition to two cases into the peritoneum in a series of 1000 CRT recipients. We believe the actual incidence is underreported, given the general impression that this complication is solely technically related. The Table3 4 5 6 summarises all reported cases of peritoneal implantation of graft ureter in the current literature.
 

Table. Summary of reported cases of peritoneal implantation of graft ureter3 4 5 6
 
All reported patients presented with postoperative anuria, with one patient developing ascites, abdominal pain, anuria, and sudden shock.5 Timing of diagnosis had been reported from immediate postoperation to few weeks later. A high level of suspicion remains the key for reaching the diagnosis. Common contributing factors identified from the literature and our case include long-term peritoneal dialysis with thickened peritoneum, and the presence of residual peritoneal fluid mimicking urine in the bladder. Therefore, this complication should be suspected in such a patient with unexplained delayed graft function. Tan et al6 suggested that an unexplained rise in ultrafiltration volume in transplanted peritoneal dialysis patients accompanied by a fall in baseline serum creatinine is highly suggestive of the diagnosis. If ureteric stenting was employed, imaging such as AXR and CT scan can help identify the position of the ureteric stent and confirm the diagnosis. Definitive diagnosis can only be established upon exploration.
 
A note of caution on ways to prevent this rare surgical complication would be more beneficial than treating it. We suggest several measures to avoid it, which have not been discussed in previous reports. Regarding the technique of ureteric implantation, the classic transvesical Leadbetter-Politano technique in which two cystostomies are required, is now replaced by the extravesical Lich-Gregoir technique which requires only one cystostomy and, hence, less bladder dissection, shorter ureteral length, and no interference with native ureteral function.7 This technique, however, may pose challenges in recipients previously on peritoneal dialysis, as the peritoneum is thickened due to exposure to dialysis fluid and episodes of peritonitis, if any. A thickened peritoneum, with the presence of residual peritoneal fluid upon incision, can easily be mistaken as the bladder during transplantation. In our practice, the bladder is filled with 80 to 100 mL of gentamicin solution before the procedure and needle aspiration test is done before ureteric implantation to aid identification of the bladder. Our case illustrated that even with these standard precautions, one may not be able to completely prevent this complication. Tagging up the extravesical tissue with parallel stay sutures on both sides of the 2 to 3 cm submucosal tunnel before creating the cystostomy will help identify the bladder and peritoneum vigilantly, avoiding shifting of the incision site to the peritoneum instead of the bladder wall after the needle test. If the bladder is scarred and non-compliant due to neuropathic bladder or prolonged anuria, identification of the junction between the peritoneum and bladder wall may become difficult. Preoperative emptying of all peritoneal dialysis fluid is advocated so that if there is nil drainage of bladder content after making the incision, entry into the abdominal cavity instead of the bladder can be suspected. Direct visualisation of the urethral catheter should be the best way to ensure the correct cavity is entered. A larger cystostomy, however, is often required and is not preferred.
 
Another innovative trick to pick up the complication, should the implantation be done already, is to notice the colour of effluent from the bladder after ureteroneocystostomy. Any urine or antibiotic solution drained in the early postoperative period is at least lightly blood-stained because of the disturbance to the mucosal edges during cystostomy. The absence of blood-stained effluent after ureteric implantation should raise the suspicion that the peritoneum, and not bladder, was opened.
 
Our report suggests that peritoneal implantation of ureter in CRT is not only technically related but also involves multiple contributing factors. A high index of suspicion is required to pick up this complication and meticulous measures should be adopted to avoid its occurrence.
 
References
1. Zavos G, Pappas P, Karatzas T, et al. Urological complications: analysis and management of 1525 consecutive renal transplantations. Transplant Proc 2008;40:1386-90. Crossref
2. Praz V, Leisinger HJ, Pascual M, Jichlinski P. Urological complications in renal transplantation from cadaveric donor grafts: a retrospective analysis of 20 years. Urol Int 2005;75:144-9. Crossref
3. Davari HR, Yarmohammadi H, Malekhosseini SA, Salahi H, Bahador A, Salehipour M. Urological complications in 980 consecutive patients with renal transplantation. Int J Urol 2006;13:1271-5. Crossref
4. Gibbons WS, Barry JM, Hefty TR. Complications following unstented parallel incision extravesical ureteroneocystostomy in 1,000 kidney transplants. J Urol 1992;148:38-40.
5. Blanco Parra M, Calviño J, Romero Burgos R, et al. Ureteral implantation in peritoneum. Exceptional complication in renal transplantation [in Spanish]. Actas Urol Esp 2002;26:579-80. Crossref
6. Tan SY, Lim CS, Teo SM, Lee SH, Razack A, Loh CS. Peritoneal implantation of ureter in a cadaveric kidney transplant recipient. Med J Malaysia 2003;58:769-70.
7. Zhao JJ, Gao ZL, Wang K. The transplantation operation and its surgical complications. In: Ortiz J, Andre J, editors. Understanding the complexities of kidney transplantation. China: InTech; 2011: 466-7. Crossref

Three cases of atypical pneumonia caused by Chlamydophila psittaci

Hong Kong Med J 2015 Jun;21(3):272–5
DOI: 10.12809/hkmj144321
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Three cases of atypical pneumonia caused by Chlamydophila psittaci
Sandy Chau, MB, BS, FHKAM (Pathology)1; Eugene YK Tso, MB, BS, FHKAM (Medicine)2; WS Leung, MB, ChB, FHKAM (Medicine)2; Kitty SC Fung, MB, ChB, FHKAM (Pathology)1
1 Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong
2 Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong
Corresponding author: Dr Sandy Chau (chauky@ha.org.hk)
 
 Full paper in PDF
Abstract
Psittacosis is a zoonotic disease caused by Chlamydophila psittaci. The most common presentation is atypical pneumonia. Three cases of pneumonia of varying severity due to psittacosis are described. All patients had a history of avian contact. The diagnosis was confirmed by molecular detection of Chlamydophila psittaci in respiratory specimens. The cases showed good recovery with doxycycline treatment. Increased awareness of psittacosis can shorten diagnostic delay and improve patient outcomes.
 
 
[Abstract in Chinese]
 
Introduction
Psittacosis is a zoonotic disease caused by Chlamydophila psittaci, an obligate intracellular pathogen belonging to the family Chlamydiaceae. Since its first description in 1879, zoonotic and enzoonotic outbreaks have been reported worldwide.1 Transmission occurs through direct contact or inhalation of aerosols from dried faeces, feather dust, or respiratory secretions of infected birds. Individuals with occupational or recreational exposure to birds like bird fanciers and veterinarians are at greatest risk of infection. Person-to-person transmission is rare.2 The disease can range from subclinical infection to fatal pneumonia. Here, we report three cases of atypical pneumonia caused by C psittaci in Hong Kong.
 
Case reports
Case 1
A 62-year-old retired male presented in March 2014 with fever, headache, myalgia, cough, and yellowish sputum for 6 days. He had underlying diabetes mellitus, hypertension, gout, and renal impairment. He visited the local bird market frequently and had purchased two parrots before onset of symptoms. The parrots were well all along. On presentation, he was alert and stable and his temperature was 38.4°C. The oxygen saturation was 96% on room air. Chest examination revealed left lower zone crepitations. Chest radiograph showed left lower zone consolidation. He was suspected of psittacosis and was treated with ceftriaxone and doxycycline. His sputum was positive for C psittaci by polymerase chain reaction (PCR). Nasopharyngeal swab and sputum were also positive for influenza A virus subtype H3 by PCR. Oseltamivir was commenced. He was afebrile the next day and was discharged after 5 days of hospitalisation. Paired serum collected 12 days apart showed rising Chlamydia group titre from 40 to 80 by complement fixation test (CFT). The parrots could no longer be traced as the patient’s son released them.
 
Case 2
A 55-year-old male construction site worker with hypertension was admitted in February 2014 with a 1-week history of fever, headache, generalised bone pain, and cough. He had travelled to Shanwei in China and bought a live chicken from a wet market 2 weeks earlier. On examination, his vital signs were stable and had a temperature of 40°C. The oxygen saturation was 98% on room air. Chest examination was normal. Chest radiograph showed right upper zone opacities. He was treated as a case of community-acquired pneumonia with amoxicillin-clavulanate, doxycycline, and oseltamivir. Sputum culture showed growth of commensals only. Nasopharyngeal aspirate (NPA) was negative for influenza viruses, Mycoplasma pneumoniae, and Chlamydophila pneumoniae by PCR. Oseltamivir was stopped. His fever subsided on day 3 and he was discharged after 4 days of hospitalisation. Complement fixation test of paired sera taken 2 weeks apart showed a rise in Chlamydia group titre from 20 to 80. Sputum was retrieved and was positive for C psittaci by PCR.
 
Case 3
A 42-year-old female chef was hospitalised in February 2014 with fever, cough, yellowish and blood-stained sputum, and breathing difficulty for 1 week. She had no underlying illness. One week prior to her admission, she had travelled to Zhaoqing in China and bought live goose and chicken from a wet market. On admission, she was in respiratory distress and her temperature was 39.2°C. The oxygen saturation was 90% on 100% supplemental oxygen via non-rebreathing mask. Chest examination yielded coarse crepitations over the right side. Chest radiograph revealed right middle and lower zone consolidation, and left patchy haziness (Fig). On the same day, she was transferred to the intensive care unit. She required mechanical ventilation and extracorporeal membrane oxygenation (ECMO). She was treated as a case of severe community-acquired pneumonia with piperacillin-tazobactam, doxycycline, and oseltamivir. Sputum culture showed growth of commensals only. Sputum, NPA, and tracheal aspirate were negative for influenza viruses, M pneumoniae, and C pneumoniae by PCR. Urine was negative for Legionella pneumophila and pneumococcal antigens. She gradually improved and was extubated 3 days later, and ECMO was stopped on day 7. She was discharged on day 24 of hospitalisation. Paired serum drawn 12 days apart showed rising Chlamydia group titre from 80 to 640 by CFT. Polymerase chain reaction for C psittaci was positive in her stored sputum.
The laboratory profiles of the three cases on admission are summarised in the Table.
 

Figure. Chest radiograph on admission shows right middle and lower zone consolidation (arrow), and patchy haziness over left lung (arrowheads) in case 3
 

Table. Laboratory parameters of our cases on admission
 
Discussion
Psittacosis is an uncommon disease in Hong Kong. Since 2008, this has been made as a statutory notifiable disease. There were 11 confirmed cases and six probable cases reported until 2013.3 In 2012, there was an outbreak involving six staff working at the New Territories North Animal Management Centre in Sheung Shui.4
 
Chlamydophila psittaci is classified into nine genotypes (A to F, E/B, M56, WC) based on outer membrane protein A gene sequences, with differential host preference and virulence among the genotypes.1 It has been described in at least 460 bird species from 30 orders.5 Birds can shed the organisms when apparently healthy or overtly ill. Patient 1 had been exposed to asymptomatic parrots, belonging to the classic culprits, the psittacine birds (parrots, parakeets, budgerigars, cockatiels). Other domestic species—for examples, turkey, pigeon, goose, duck, chicken—can be affected and are often overlooked as potential reservoirs of infection.6 In patients 2 and 3, psittacosis was not suspected initially although the patients had been exposed to poultry in China. Chlamydophila psittaci is an emerging pathogen among chicken.7 In China, the prevalence of infection among market-sold chickens, ducks, and pigeons has been reported to be 13.32%, 38.92% and 31.09%, respectively.8 The substantial zoonotic transmission risk from domestic species should also be recognised.
 
Psittacosis is a systemic illness that affects several organ systems, and atypical pneumonia as in our cases is the most common manifestation. Patients typically present with influenza-like symptoms, which include high fever, headache, myalgia, and dry cough. Patient 3 complained of blood-stained sputum, which may occur occasionally.1 9 The headaches can be so severe as to suggest meningitis on presentation. Diarrhoea is common and can be the chief presenting complaint. Relative bradycardia, Horder’s spots, and splenomegaly are characteristic physical signs. There may be disparity between the auscultatory findings and radiographic changes of pneumonia. Segmental consolidation in lower lobe is the most common radiographic abnormality although normal chest radiograph has been reported in over 20% of cases. Hilar lymphadenopathy and pleural effusion are rare.10 The white cell count is usually normal or slightly raised, with mildly abnormal liver function. Our case presentations were consistent with psittacosis. However, it is indistinguishable clinically from other causes of atypical pneumonia like C pneumoniae. The severity ranged from mild-to-severe pneumonia requiring intensive care management and ECMO in our cases. Patient 1 had mild illness although co-infected with influenza A. This diversity of presentation is in agreement with other case series.9 The mortality rate can be approximately 15% to 20% without appropriate treatment but if properly treated, it is rarely fatal.11 Extrapulmonary complications such as endocarditis, myocarditis, renal disease, hepatitis, keratoconjunctivitis, arthritis, and encephalitis have also been described.
 
Chlamydophila psittaci is not covered during routine bacterial or viral workup. Definitive diagnosis can only be established by culture, serology, or PCR specifically targeting on C psittaci. Culture is time-consuming and requires level-3 biosafety facilities. Common serological assays include CFT, enzyme-linked immunosorbent assay, and microimmunofluorescence (MIF) test. The assays are neither sensitive nor specific but MIF test is regarded as more specific.12 However, there are still considerable cross-reactions between different species of the Chlamydiaceae family.1 Besides, a convalescent serum obtained at least 2 weeks apart is required to demonstrate the 4-fold rise in titre. In patient 1, the elevation in CFT titre was not significant and therefore diagnosis may be missed if relying on serology alone. Early use of doxycycline in this patient might have blunted the antibody response.13 In patients 2 and 3, serology results were available only retrospectively; PCR for C psittaci was performed subsequently to confirm the diagnosis. In our cases, a nested PCR based on 16S rRNA gene was used. The first-step PCR is genus-specific, followed by the second-step PCR that can detect C psittaci specifically.14 This method was demonstrated to be sensitive and specific for detection of C psittaci. When encountering respiratory illness with suspicion of psittacosis, PCR testing on respiratory specimens can offer a rapid and specific diagnosis.
 
Tetracyclines, in particular doxycycline, are considered to be the treatment of choice. In patients presenting with community-acquired pneumonia, addition of doxycycline to a beta-lactam–based empirical regimen can provide coverage for both psittacosis and other atypical pathogens. Defervescence usually takes place within 48 hours of treatment. Our patients showed significant improvement by day 3 of doxycycline treatment. The commonly recommended duration of treatment is at least 10 to 21 days to prevent relapse.9 Macrolides can be used as alternative therapy, but may be less efficacious in severe cases and gestational psittacosis.6 Although quinolones have in-vitro activity against C psittaci, their clinical effectiveness remains to be determined.6
 
Conclusion
Psittacosis often goes unrecognised because of the lack of distinctive symptoms and clinical suspicion. In patients with atypical pneumonia, a history of exposure to birds gives a very valuable diagnostic clue. Early diagnosis with PCR testing and timely initiation of appropriate antibiotics can reduce patient morbidity and mortality.
 
Acknowledgement
We thank the Public Health Laboratory Services Branch of the Centre for Health Protection for providing the laboratory testing of psittacosis.
 
References
1. Beeckman DS, Vanrompay DC. Zoonotic Chlamydophila psittaci infections from a clinical perspective. Clin Microbiol Infect 2009;15:11-7. Crossref
2. Hughes C, Maharg P, Rosario P, et al. Possible nosocomial transmission of psittacosis. Infect Control Hosp Epidemiol 1997;18:165-8. Crossref
3. Statistics on communicable diseases. Available from: http://www.chp.gov.hk/en/notifiable1/10/26/43.html. Accessed 25 Feb 2015.
4. Psittacosis outbreak in an animal management centre, 2012. Communicable Diseases Watch 2013;10:9-10. Available from: http://www.chp.gov.hk/files/pdf/cdw_compendium_2013.pdf. Accessed 25 Feb 2015.
5. Kaleta EF, Taday EM. Avian host range of Chlamydophila spp. based on isolation, antigen detection and serology. Avian Pathol 2003;32:435-61. Crossref
6. Stewardson AJ, Grayson ML. Psittacosis. Infect Dis Clin North Am 2010;24:7-25. Crossref
7. Lagae S, Kalmar I, Laroucau K, Vorimore F, Vanrompay D. Emerging Chlamydia psittaci infections in chickens and examination of transmission to humans. J Med Microbiol 2014;63:399-407. Crossref
8. Cong W, Huang SY, Zhang XY, et al. Seroprevalence of Chlamydia psittaci infection in market-sold adult chickens, ducks and pigeons in north-western China. J Med Microbiol 2013;62:1211-4. Crossref
9. Yung AP, Grayson ML. Psittacosis—a review of 135 cases. Med J Aust 1988;148:228-33.
10. Coutts II, Mackenzie S, White RJ. Clinical and radiographic features of psittacosis infection. Thorax 1985;40:530-2. Crossref
11. Smith KA, Campbell CT, Murphy J, Stobierski MG, Tengelsen LA. Compendium of measures to control Chlamydophila psittaci (formerly Chlamydia psittaci) infection among humans (psittacosis) and pet birds (avian chlamydiosis), 2010 National Association of State Public Health Veterinarians (NASPHV). J Exotic Pet Med 2011;20:32-45. Crossref
12. Petrovay F, Balla E. Two fatal cases of psittacosis caused by Chlamydophila psittaci. J Med Microbiol 2008;57:1296-8. Crossref
13. Heddema ER, van Hannen EJ, Duim B, et al. An outbreak of psittacosis due to Chlamydophila psittaci genotype A in a veterinary teaching hospital. J Med Microbiol 2006;55:1571-5. Crossref
14. Messmer TO, Skelton SK, Moroney JF, Daugharty H, Fields BS. Application of a nested, multiplex PCR to psittacosis outbreaks. J Clin Microbiol 1997;35:2043-6.

Technical considerations for ligation of ruptured hepatic artery aneurysm: is arterial reconstruction necessary?

Hong Kong Med J 2015 Jun;21(3)276–9
DOI: 10.12809/hkmj144260
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Technical considerations for ligation of ruptured hepatic artery aneurysm: is arterial reconstruction necessary?
S Lam, MB, BS, MRes (Med)1; Albert CY Chan, FRCS (Edin), FCSHK2; Ronnie TP Poon, FRCS (Edin), FCSHK2
1 Department of Surgery, Queen Mary Hospital, Pokfulam, Hong Kong
2 Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
Corresponding author: Dr S Lam (lamshi07@gmail.com)
 
 Full paper in PDF
Abstract
Ruptured hepatic artery aneurysm is a rare life-threatening condition. Open surgery with ligation of the aneurysm is the treatment of choice if the patient presents with haemodynamic instability. Controversies exist on whether hepatic artery reconstruction is needed after exclusion of the aneurysm. Involvement of the gastroduodenal artery origin was proposed as an indication for reconstruction, but this might be difficult to ascertain upon laparotomy. Recent studies showed that arterial ligation distal to the gastroduodenal artery origin does not necessarily result in ischaemic liver injury, implying that reconstruction in such cases may not be required, especially in a haemodynamically unstable patient. A patient with common hepatic artery aneurysm involving the gastroduodenal artery origin presented with rupture and underwent aneurysm ligation. Adequacy of intrahepatic arterial flow was determined by intra-operative Doppler ultrasonography and arterial reconstruction was not performed. The technical considerations during the operative management of ruptured hepatic artery aneurysms are discussed.
 
 
[Abstract in Chinese]
 
Introduction
Hepatic artery aneurysm (HAA) is an uncommon condition that can present with life-threatening haemorrhage. In case of catastrophic intraperitoneal rupture, laparotomy with ligation of the aneurysm is often the treatment of choice due to its rapid access and ability to secure control of the extravasation site. Controversy exists whether hepatic artery should be reconstructed after ligation of the aneurysm, especially when distal ligation is performed on the hepatic artery proper. We herein describe the technical considerations during the operative management of a patient with ruptured HAA.
 
Case report
A 69-year-old male presented to Queen Mary Hospital, Hong Kong, with a 3-week history of epigastric pain in December 2010. A contrast-enhanced computed tomography (CT) of the abdomen showed a common HAA with involvement of the root of gastroduodenal artery (GDA; Fig 1a) but there was no evidence of contrast leakage or haematoma formation at the time of diagnosis. Complete blood profile showed evidence of inflammation that included mild leukocytosis with neutrophil predominance, thrombocytosis, and mildly elevated erythrocyte sedimentation rate. Serum biochemistry showed elevated γ-glutamyl transpeptidase and C-reactive protein. Screening for vasculitis and infection was unremarkable.
 

Figure 1. Computed tomography images
(a) Preoperative scan showing an aneurysm involving the gastroduodenal artery (arrowhead); (b) 2-month postoperative surgical clip marks the site of proximal neck ligation of common hepatic artery (arrow); the gastroduodenal artery (arrowhead) is discontinuous from the hepatic artery proper; (c) 8-month postoperative pericholedochal collateral vessels (arrow) along the common bile duct (arrowhead)
 
Three days later, however, the patient developed generalised peritonitis complicated by hypovolaemic shock during the workup for this condition in the hospital. There was an acute drop in haemoglobin level from 150 g/L to 125 g/L. A diagnosis of rupture of the common HAA was made clinically and an emergency laparotomy was performed.
 
On entering the peritoneal cavity, 5 L of hemoperitoneum was recovered, and after four-quadrant packing of the peritoneal cavity, supracoeliac aortic clamping was performed to secure temporary haemostasis. The lesser sac was entered and a ruptured 4 x 3 cm fusiform aneurysm of the common hepatic artery surrounded by inflamed tissues cranial to the pancreatic head region was identified. The proximal and distal neck of the aneurysm was subsequently isolated and encircled by tape without further dissection at the hepatoduodenal ligament. After release of the aortic clamp, the distal neck of the aneurysm at the hepatic artery proper was test clamped and Doppler ultrasonography was performed, which confirmed good biphasic flow in both the right and left hepatic arteries. The aneurysm was then ligated and suture-transfixed at its proximal and distal neck region (Fig 2).
 

Figure 2. Intra-operative photo showing the liver (L), gallbladder (G), duodenum (D), hepatic artery proper (arrow) and the laid-open common hepatic artery aneurysm sac (arrowheads) after distal ligation (sutures)
 
In the postoperative period, the alanine and aspartate transaminase levels were elevated to 1607 U/L and >3000 U/L, respectively. Both the liver parenchymal enzymes returned to normal levels 3 weeks after the procedure. A short course of renal replacement therapy was required for the acute renal injury sustained during the shock. Otherwise, the patient made an uneventful recovery. Pathological examination of the aneurysm wall showed infiltration of lymphocytes and neutrophils but there was no evidence of infection.
 
Follow-up CT performed at 2 and 8 months postoperatively showed arterial collateral formation along the porta hepatis, and there was no evidence of previous liver infarction (Figs 1b and 1c).
 
Discussion
Hepatic artery aneurysm is a rare condition with an estimated prevalence of 0.1% according to autopsy series,1 and incidence of 0.002%.2 The majority (75%) of cases are incidentally diagnosed, and pain in the right upper quadrant or epigastrium is the most common presenting symptom.1 Rupture is the second most common mode of presentation and accounts for 14% of the newly diagnosed HAAs.2
 
The reported mortality rate for ruptured HAA is 21% to 43%,2 3 and the key to successful resuscitation is timely control of the ruptured site. Although endovascular exclusion of HAAs has a reported success rate of up to 100%,4 open surgery is often the treatment of choice if the exsanguinating haemorrhage does not permit a failed trial of endoluminal haemostasis.
 
The objectives of open surgery are to exclude the diseased artery segment and preserve the hepatic arterial inflow. It is generally accepted that aneurysms of the common hepatic artery which do not involve the GDA can be simply ligated without reconstruction of inflow to the hepatic artery proper because the latter is supplied by the reverse flow from the GDA.5 For aneurysms involving GDA or distal to its origin, the conventional advocate is to reconstruct hepatic arterial inflow after ligation or resection of the aneurysm to avoid the risk of ischaemic injury to the liver.6 Depending on the morphology and size of the aneurysm, inflow restoration may take the form of aneurysmectomy with patch graft repair or exclusion of aneurysm with coeliac or aorto-hepatic bypass grafting. Autogenous saphenous vein is the preferred graft, although a dacron prosthetic graft can also be used.6 In our patient, because of the clinical suspicion of an infective aetiology for the ruptured aneurysm and due to the satisfactory hepatic arterial flow during intra-operative ultrasound, arterial reconstruction was not considered.
 
Graham and Cannel7 had reviewed that accidental hepatic artery ligation would result in greater than 50% mortality when the site of ligation is distal to the GDA. In later studies, however, such a high mortality rate was not observed with hepatic artery ligation during iatrogenic injuries or therapeutic procedures to ‘de-arterialise’ tumour-laden livers.5 8 9 It is believed that the liver is protected from ischaemic insults after hepatic artery ligation by a buffer response of the portal venous system. The portal vein maintains the supply of 70% of hepatic inflow and 50% of hepatic oxygen consumption during acute hepatic artery interruption, before compensatory arterial supply develops.6 With time, a multitude of arterial collateral channels can develop to compensate for the interruption of original arterial inflow. In fact, postoperative CT scan at 8 months in our patient clearly showed collateral formation via the pericholedochal route (Fig 1c). Besides, Michels10 has described 26 potential sites of collateral arterial supplies to the liver originating from the celiac trunk, superior mesenteric artery and intrathoracic arteries, routing via the hepatoduodenal ligament, hepatogastric ligament, omentum, retroperitoneum, falciform ligament, and diaphragmatic connections. Collateral formation is observed after ligation of hepatic arteries in angiographic studies as early as 10 hours after ligation.5 Moreover, replaced or accessory arterial supplies to the left or right hepatic lobes are present in about 30% of the general population,5 11 rendering feasible supply to the contralateral lobe via the interlobar anastomosis at the liver hilum. The clinical relevance of such vascular recovery potential was demonstrated by Chirica et al,12 wherein the technique of simple aneurysm ligation with minimal dissection in the hepatoduodenal ligament was adopted so as to preserve the potential arterial collaterals and hence avoiding the need for reconstruction of the extirpated hepatic artery in three out of four patients in their series of HAAs with GDA involvement.
 
Establishment of arterial collaterals, however, is a latent process and the anatomical information on the presence of aberrant or replaced hepatic arterial supply may not be readily available at the time of laparotomy for a ruptured aneurysm. In this situation, intra-operative Doppler ultrasonography is a convenient tool for evaluation of intrahepatic arterial flow. In transplanted livers, a normal Doppler waveform of the hepatic artery includes a rapid upstroke with an acceleration time of <80 ms, a continuous diastolic flow giving a resistive index between 0.5 and 0.7, and a peak systolic velocity of <2 m/s; any deviation from normality from any of these parameters is suggestive of hepatic artery stenosis and predictive of subsequent ischaemic bile duct injury.13 Perhaps, the same criteria can be adopted to assess the arterial sufficiency in a native liver. Back bleed from distal cut end of hepatic artery and cyanosis of hepatic lobe should be counted with caution as these have been reported to be inaccurate in predicting adequate perfusion or subsequent ischaemic injury, respectively.14
 
Conclusion
Simple ligation of the hepatic artery is considered safe and effective in the treatment of ruptured HAA. The establishment of arterial collaterals should be expected given that the hepatoduodenal ligament is not severely disrupted. The use of intra-operative ultrasound facilitates the decision-making in devising the operative strategy for this condition.
 
Declaration
No conflict of interest was declared by the authors.
 
References
1. Arneson MA, Smith RS. Ruptured hepatic artery aneurysm: case report and review of literature. Ann Vasc Surg 2005;19:540-5. Crossref
2. Abbas MA, Fowl RJ, Stone WM, et al. Hepatic artery aneurysm: factors that predict complications. J Vasc Surg 2003;38:41-5. Crossref
3. Shanley CJ, Shah NL, Messina LM. Common splanchnic artery aneurysms: splenic, hepatic, and celiac. Ann Vasc Surg 1996;10:315-22. Crossref
4. Tulsyan N, Kashyap VS, Greenberg RK, et al. The endovascular management of visceral artery aneurysms and pseudoaneurysms. J Vasc Surg 2007;45:276-83. Crossref
5. Mays ET, Wheeler CS. Demonstration of collateral arterial flow after interruption of hepatic arteries in man. N Engl J Med 1974;290:993-6. Crossref
6. Tygstrup N, Winkler K, Mellemgaard K, Andreassen M. Determination of the hepatic arterial blood flow and oxygen supply in man by clamping the hepatic artery during surgery. J Clin Invest 1962;41:447-54. Crossref
7. Graham RR, Cannel D. Accidental ligation of the hepatic artery. Br J Surg 1933;20:566-79. Crossref
8. Ariyan S, Cahow CE, Greene FL, Stansel HC Jr. Successful treatment of hepatic artery aneurysm with erosion into the common duct. Ann Surg 1975;182:169-72. Crossref
9. Brittain RS, Marchioro TL, Hermann G, Waddell WR, Starzl TE. Accidental hepatic artery ligation in humans. Am J Surg 1964;107:822-32. Crossref
10. Michels NA. Collateral arterial pathways to the liver after ligation of the hepatic artery and removal of the celiac axis. Cancer 1953;6:708-24. Crossref
11. Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited: digital subtraction angiography performed in 600 patients. Radiology 2002;224:542-7. Crossref
12. Chirica M, Alkofer B, Sauvanet A, Vullierme MP, Levy Y, Belghiti J. Hepatic artery ligation: a simple and safe technique to treat extrahepatic aneurysms of the hepatic artery. Am J Surg 2008;196:333-8. Crossref
13. Crossin JD, Muradali D, Wilson SR. US of liver transplants: normal and abnormal. Radiographics 2003;23:1093-114. Crossref
14. Mathisen DJ, Athanasoulis CA, Malt RA. Preservation of arterial flow to the liver: goal in treatment of extrahepatic and post-traumatic intrahepatic aneurysms of the hepatic artery. Ann Surg 1982;196:400-11. Crossref

Minimally invasive enteroscopically guided small bowel resection

Hong Kong Med J 2015 Jun;21(3)280–2
DOI: 10.12809/hkmj144270
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Minimally invasive enteroscopically guided small bowel resection
Tommy CH Man, MB, BS; KC Ng, MB, BS; KW Wong, MB, BS; Francis PT Mok, MB, BS
Department of Surgery, Caritas Medical Centre, Shamshuipo, Hong Kong
Corresponding author: Dr Tommy CH Man (manchunhin@gmail.com)
 
 Full paper in PDF
Abstract
Localisation of small bowel pathology is often difficult, especially intramural small bowel lesions. Even with the use of laparoscopy, visualisation of small bowel lesion is not always possible. The most accurate method to identify such a lesion is by laparotomy with direct visualisation and palpation of the lesion. However, the recent trend in surgical development aims for minimally invasive procedures while keeping the excision of surgical pathology safe and complete, with less surgical trauma. This report illustrates a case of minimally invasive enteroscopically guided small bowel resection.
 
 
[Abstract in Chinese]
 
Case report
A 64-year-old male with a history of hepatic carcinosarcoma had his right hemihepatectomy done in 2011. The resection margins were clear and interval computed tomography (CT) scans did not reveal any recurrence.
 
One year after the surgery he was admitted for complaints of non-specific abdominal pain, melena, and dizziness. On admission, the haemoglobin level was only 50 g/L although his oesophagogastroduodenoscopy and colonoscopy were normal. Capsule endoscopy was performed and this showed a fungating tumour in the jejunum with evidence of bleeding. Another CT scan was arranged which confirmed that there was a 2.5-cm intraluminal lesion in the small bowel, suggesting a probable occurrence of gastro-intestinal stromal tumour.
 
Subsequently, single-port laparoscopic resection of the small bowel tumour under single-balloon enteroscopic guidance was performed. The patient was operated on under general anaesthesia in supine position with prophylactic antibiotics. The single-balloon enteroscope (Olympus SIF-Q260; Olympus Medical Systems Corp, Japan) was used to locate the site of tumour (Fig 1a). The lesion was marked with endomarker (Fig 1b) and lipiodol injection, and the enteroscope was left in situ in order to guide the site of skin incision. Fluoroscopy and transillumination of the small bowel at the site of lesion confirmed that the tumour was situated in the left upper quadrant of the abdomen (Figs 2a and 2b).
 

Figure 1. Tumour at proximal jejunum (a) before and (b) after endomarker injection
 

Figure 2. (a) Fluoroscopy scan and (b) transillumination of tumour. (c) Retrieval of small bowel and (d) length of incision
 
A 2-cm incision was made for laparoscopic procedure using a Hassan laparoscopic port that was inserted with an 8-degree laparoscope with working channel (OLYMPUS A5252A laparoscope; Olympus Medical Systems Corp, Germany). Laparoscopy procedure confirmed that there were no suspicious hepatic and peritoneal nodules. The diseased part of the small bowel was taken out using a grasper through the working channel after extension of the skin wound (Fig 2c). Usual small bowel resection was done with primary anastomosis using linear staplers and the entire procedure lasted for about 225 minutes.
 
The patient tolerated the whole procedure well and his recovery was satisfactory. He gradually resumed oral feeding and was fit for discharge on day 3 after the procedure.
 
Discussion
Midline laparotomy incision is often a straightforward procedure for treatment and resection of small bowel lesions. The long laparotomy wound, however, may cause a lot of pain, leading to prolonged hospital stay and more analgesic requirement that may impair respiratory function especially in patients with advanced age and multiple co-morbidities.
 
Although capsule endoscopy for identification of small bowel pathologies1 2 has become prevalent in patients with occult gastro-intestinal bleeding, sometimes it renders the operation difficult to accurately determine the site of lesion and locate the tumour.
 
The recent advances in surgical technology and development of new techniques have made minimally invasive procedures possible, like robotic surgery and endoscopic resection. However, the installation of these surgical instruments takes up a lot of space in the operating theatre and increases the cost of enhancement, not to mention the huge maintenance cost.3 4 As such, we present a case of minimally invasive small bowel resection which is cost-effective to be adopted by most hospitals.
 
To recap, the aim of minimally invasive surgery is to reduce surgical morbidity with smaller and less wound while maintaining pathological clearance and safety. In our design, the use of enteroscope provided accurate localisation of the pathology by direct visualisation.5 After confirming the position of the pathology, the skin incision could be precisely made on top of the lesion. Before excising the lesion, laparoscopy was also performed to make sure that there was no intra-abdominal metastatic deposit. The wound was extended to 4.5 cm and this allowed the diseased small bowel to be retrieved for resection as in an open procedure (Fig 2d). The instruments used are readily available in most hospitals and the procedure can be performed at a relatively lower cost.
 
Single-balloon enteroscope, the procedure used in our case, is a recently developed technology for diagnosing small bowel pathology. The setup of this safe enteroscope is simple.6 Moreover, some evidence bore out that the learning curve of single-balloon enteroscope is insignificant.7 8 Previous study also showed that single-balloon enteroscope provided a diagnostic yield similar to double-balloon enteroscope which requires more technical skills.9
 
In this operation, three types of localisation methods were adopted after position of the tumour was confirmed by enteroscopy. These included lipiodol injection, transillumination to localise the incision site, and endomarker injection to find out precisely where the tumour was located.
 
Lipiodol injection at the site of tumour allows localisation of lesion under fluoroscopic guidance, which is useful to guide the site for skin incision. It can be done before operation, hence saves time during intra-operative enteroscopy. The exact position of the tumour, however, may not be easily located by laparoscope after identification of the incision site.
 
In such situations, injection of endomarker before operation is recommended during laparoscopy as this enables better visualisation of the portion of the diseased bowel to be retrieved for further resection. However, endomarker cannot replace lipiodol in localisation of lesion as it is not radio-opaque and cannot aid localisation of skin incision site.
 
Alternatively, transillumination using enteroscope allows real-time localisation of the incision site and this is superior to merely injecting lipiodol. However, the risk of complications arising from intra-operative enteroscope may be hiked up and the operating time may be extended.
 
To facilitate the operation and shorten the time required, preoperative enteroscopy rather than intra-operative enteroscopy should be employed. The injection of lipiodol and endomarker can be done before operation. As an initial attempt of our de-novo technique in this case, we decided to use intra-operative enteroscopy with transillumination for real-time tumour localisation even though the operating time was inevitably prolonged.
 
In addition to the above methods, the use of endoclip is considered a possible option for accurate localisation. Since endoclip is radio-opaque, it can serve both purposes for incision site and tumour localisation under fluoroscopic guidance. Nevertheless, the accuracy could be affected due to the risk of dislodgement of these endoclips.
 
Conclusion
Enteroscope is a safe option for guiding minimally invasive small bowel resection with accurate localisation of pathology. There are different ways for localisation including the use of endomarker, lipiodol injection, transillumination as well as endoclip. Large-scale studies using these techniques should be considered in order to understand the efficacy of such newer methods.
 
References
1. Mavrogenis G, Coumaros D, Bellocq JP, Leroy J. Detection of a polypoid lesion inside a Meckel’s diverticulum using wireless capsule endoscopy. Endoscopy 2011;43 Suppl 2 UCTN:E115-6.
2. Mavrogenis G, Coumaros D, Lakhrib N, Renard C, Bellocq JP, Leroy J. Mixed cavernous hemangioma-lymphangioma of the jejunum: detection by wireless capsule endoscopy. Endoscopy 2011;43 Suppl 2 UCTN:E217-8.
3. Amodeo A, Linares Quevedo A, Joseph JV, Belgrano E, Patel HR. Robotic laparoscopic surgery: cost and training. Minerva Urol Nefrol 2009;61:121-8.
4. Kim CW, Baik SH. Robotic rectal surgery: what are the benefits? Minerva Chir 2013;68:457-69.
5. Ress AM, Benacci JC, Sarr MG. Efficacy of intraoperative enteroscopy in diagnosis and prevention of recurrent occult gastrointestinal bleeding. Am J Surg 1992;163:94-9. Crossref
6. Yoshiya S, Sugimachi K, Nakamura S, et al. Preoperative diagnostic value of single-balloon enteroscopy for successful surgical treatment of three independent-origin gastrointestinal malignant tumors: report of a case. Surg Today 2011;41:1007-10. Crossref
7. Upchurch BR, Sanaka MR, Lopez AR, Vargo JJ. The clinical utility of single-balloon enteroscopy: a single-center experience of 172 procedures. Gastrointest Endosc 2010;71:1218-23. Crossref
8. Tsujikawa T, Saitoh Y, Andoh A, et al. Novel single-balloon enteroscopy for diagnosis and treatment of the small intestine: preliminary experiences. Endoscopy 2008;40:11-5. Crossref
9. Domagk D, Mensink P, Aktas H, et al. Single- vs. double-balloon enteroscopy in small-bowel diagnostics: a randomized multicenter trial. Endoscopy 2011;43:472-6. Crossref

Fatal bilateral lower-limb deep vein thrombosis and pulmonary embolism following single digit replantation

Hong Kong Med J 2015 Jun;21(3):283–5
DOI: 10.12809/hkmj144262
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Fatal bilateral lower-limb deep vein thrombosis and pulmonary embolism following single digit replantation
Anderson SM Leung, MB, BS, MHKICBSC; Margaret WM Fok, FRCSEd(Orth), FHKAM (Orthopaedic Surgery); Boris KK Fung, FRCSEd(Orth), FHKAM (Orthopaedic Surgery)
Department of Orthopaedics and Traumatology, Queen Mary Hospital, Pokfulam, Hong Kong
Corresponding author: Dr Margaret WM Fok (margaret_fok@yahoo.com)
 
 Full paper in PDF
Abstract
Venous thromboembolism in hand surgery is rare. There is no report in the literature on postoperative mortality from venous thromboembolism following microsurgery in upper limbs. We report the case of a 56-year-old Chinese man who died from pulmonary embolism as a result of bilateral lower-limb deep vein thrombosis following prolonged surgery under general anaesthesia after replantation of a finger. This case raises awareness of the need for precautions against venous thromboembolism following prolonged microsurgery and identification of high-risk patients.
 
 
[Abstract in Chinese]
 
Introduction
Venous thromboembolism (VTE) is a condition that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The formation of thrombi is associated with the Virchow’s triad, ie circulatory stasis, vascular wall injury, and a hypercoagulable state. Most data of VTE in orthopaedic surgeries are based on studies of patients who undergo hip or knee arthroplasty. The risk of VTE following lower-limb surgery is noted to be considerably higher than those following upper-limb surgery. To date, there has been no evidence to support the prescription of VTE prophylaxis in upper-limb operations.
 
Case report
In June 2013, a 56-year-old, non-obese, Chinese carpenter, who enjoyed good past health and was a non-smoker, sustained injuries to both his left ring finger and little finger while using an electric saw. His left ring finger was amputated at the level of the middle phalanx and his little finger was nearly amputated at the distal interphalangeal joint level. No other site of injury was noted (Fig a). He presented to our hospital 1 hour after the injury. Upon arrival he was haemodynamically stable.
 

Figure. (a) Amputated left ring finger and near-amputated left little finger. (b) Left ring finger stump with severe soft tissue contamination
 
Due to the severe soft tissue contamination of the finger stumps (Fig b), options of either replantation or revision amputation for the ring finger was discussed with the patient. Subsequent emergency operation was arranged for attempted replantation of his ring finger, and wound debridement and fixation of his left little finger. Revascularisation of the ring finger was attempted thrice, including use of a vein graft. However, due to the inability to achieve sustained blood flow to the amputated stump, revision amputation was performed. Meanwhile, the open wound of the little finger was debrided, and the fracture of the finger was temporarily fixed with axial K wire. The operation lasted 6 hours 25 minutes, with a total anaesthetic time of 7 hours 12 minutes. The fluid balance was +2450 mL. He regained full consciousness in the recovery room, with good breathing and oxygen saturation. Antibiotics were continued and he was transferred back to a general ward.
 
The operation was completed at 4 am the next day and his vital signs remained stable throughout. He offered no complaints in the morning round and was able to mobilise and walk to the washroom where he sustained an unwitnessed fall. He had neither preceding chest pain, headache, nor swelling and pain over his lower limbs, and did not lose consciousness. He developed tachycardia, tachypnoea, and desaturation after being helped to his bed. Echocardiogram revealed sinus tachycardia. He started developing chest discomfort with subsequent witnessed arrest 40 minutes later. Cardiac monitoring revealed pulseless electrical activity. Cardiopulmonary resuscitation was started immediately with injection of adrenaline. Bedside echocardiogram revealed no pericardial effusion but there was no response to resuscitation and the patient succumbed 35 minutes later. Postmortem examination revealed bilateral DVT in the calf muscles. Both lungs were markedly congested, with occluding thromboemboli noted in the hilar main pulmonary arteries and their main branches. No other thromboemboli were noted.
 
Discussion
Lower limb surgery is a risk factor for VTE events. The prevalence of DVT in patients who undergo hip fracture surgery and hip or knee arthroplasty ranges from 40% to 60%.1 2 Clinical or fatal PE in Hong Kong Chinese patients is even rarer.2
 
With regard to VTE following upper-limb surgery, nine VTE events have been reported. These comprised seven PEs following total elbow arthroplasty (of which three were fatal), one non-fatal PE after distal radius fixation following acute fracture, and one non-fatal PE following revision osteosynthesis of the proximal diaphysis of ulna.3 There has been no reported incidence in the literature of VTE following microsurgery.
 
It is difficult to determine whether microsurgery is completely risk-free for VTE. Prolonged surgery may involve prolonged immobilisation and blood loss that in turn increases the risk of VTE, based on Virchow’s triad. It is thus possible that prophylaxis for VTE is necessary in microsurgery when the operating time is expected to be long, for instance, in finger replantations or free-flap surgeries.
 
Currently there is no guideline on VTE prophylaxis for microsurgeries. The British Society for Surgery of the Hand4 considers upper-limb procedures under general anaesthesia for more than 90 minutes and/or with one risk factor for VTE (Box3) as moderate-risk procedures. It recommends use of mechanical compression devices in the operating room and/or until the patient becomes ambulatory. With the risk of bleeding in mind, low-molecular-weight heparin (LMWH) may be started no less than 6 hours postoperatively in selected patients and continued until they are fully ambulatory.3 None of these recommendations apply specifically to hand or microsurgeries.
 

Box. Risk factors for venous thromboembolism3
 
In addition to LMWH, the National Institute for Health and Care Excellence clinical guideline and the American College of Chest Physicians (ACCP) also mention the newer non–vitamin K antagonist oral anticoagulants (NOACs).5 This group of drugs is associated with a rapid onset of action and predictable pharmacokinetics and pharmacodynamics. There are also fewer interactions with food and other drugs. The ACCP recommends the use of VTE prophylaxis for a minimum of 10 to 14 days following major orthopaedic surgery. In patients who undergo total joint replacement, the ACCP suggests the use of LMWH in preference to other agents (eg fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin, adjusted-dose vitamin K antagonist or aspirin), irrespective of the concomitant use of an intermittent pneumatic compression device. For those patients who refuse injections, apixaban or dabigatran is recommended. However, the available studies (eg RE-MODEL trial, RECORD trial and ADVANCE-2 study) and guidelines for VTE prophylaxis focus on total joint replacement surgeries.6 There are no recommendations on the use of NOACs in microsurgeries.
 
When prescribing VTE prophylaxis, it is important to balance the associated benefits and risks. In the case of mechanical compression, in view of its low-risk profile, it should be offered to all patients who undergo prolonged microvascular procedures, for example replantation, until they are fully ambulatory. The application of mechanical compression on both lower limbs may nonetheless be limited if donor sites for blood vessels and other tissues are anticipated from a lower limb.
 
Based on available evidence, we suggest that all patients who undergo microsurgery should have mechanical compression prophylaxis. Additional pharmacological prophylaxis should be considered for those who are at relatively high risk of developing VTE, for example, patients who have more than one risk factor, those in whom upper limb or tumour surgery will exceed 90-minute duration, and/or those in whom there will be prolonged postoperative immobilisation.
 
References
1. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):381S-453S.
2. Mok CK, Hoaglund FT, Rogoff SM, Chow SP, Ma A, Yau AC. The incidence of deep vein thrombosis in Hong Kong Chinese after hip surgery for fracture of the proximal femur. Br J Surg 1979;66:640-2. Crossref
3. Roberts DC, Warwick DJ. Venous thromboembolism following elbow, wrist and hand surgery: a review of the literature and prophylaxis guidelines. J Hand Surg Eur Vol 2014;39:306-12. Crossref
4. The British Society for Surgery of the Hand. VTE Guidelines. Available from: http://www.bssh.ac.uk/education/guidelines/vteguidelines. Accessed 2 Jul 2012.
5. Beyer-Westendorf J, Ageno W. Benefit-risk profile of non–vitamin K antagonist oral anticoagulants in the management of venous thromboembolism. Thromb Haemost 2015;113:231-46. Crossref
6. Saraf K, Morris P, Garg P, Sheridan P, Storey R. Non–vitamin K antagonist oral anticoagulants (NOACs): clinical evidence and therapeutic considerations. Postgrad Med J 2014;90:520-8. Crossref

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings

Hong Kong Med J 2015 Apr;21(2):183–6
DOI: 10.12809/hkmj134208
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Helicobacter pylori–negative gastric mucosa–associated lymphoid tissue lymphoma: magnifying endoscopy findings
TT Law, FRCSEd, FHKAM (Surgery); Daniel Tong, MS, PhD; Sam WH Wong, FRCSEd, FHKAM (Surgery); SY Chan, FRCSEd, FHKAM (Surgery); Simon Law, MS, FRCSEd
Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
Corresponding author: Prof Simon Law (slaw@hku.hk)
 Full paper in PDF
Abstract
Gastric mucosa–associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori–negative gastric mucosa–associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori–eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa–associated lymphoid tissue lymphoma and its management are reviewed.
 
 
[Abstract in Chinese]
 
Introduction
Primary extranodal low-grade B cell lymphoma of the mucosa-associated lymphoid tissue (MALToma) of stomach is uncommon. The clinical presentation is variable and there is no endoscopic hallmark. Magnifying endoscopy (ME) may help in the diagnosis of gastric MALToma. Herein we report the case of a patient who had gastric MALToma diagnosed by ME.
 
Case report
A 64-year-old woman had a history of cancer of alveolus that was in remission. She was considered at increased risk of developing squamous cell carcinoma of the upper aero-digestive tract; therefore, she was referred to us for endoscopic screening in May 2012. On white light endoscopy, a well-demarcated erythematous zone measuring 3 cm in size was identified at the distal greater curvature of the stomach (Fig 1a). To further delineate this suspicious lesion, ME combined with narrow-band imaging (NBI) was used. Magnifying endoscopy was performed with a zoom endoscope (GIF-Q260Z; Olympus Hong Kong and China Ltd, China) which has a magnifying power of 80 times. The tip of the endoscope was mounted with a transparent cap for the purpose of focusing. Under ME in combination with NBI, a non-structural area, ie, complete or almost-complete disappearance of gastric crypt epithelium and abnormal mucosal capillary pattern was identified (Fig 1a). Biopsy of the suspicious zone revealed atypical lymphoid cells with lymphoepithelial lesion formation. Immunohistochemical stains confirmed that the atypical lymphoid cells were positive for B cell marker CD20 (pan-B-cell marker: L26, Dako, UK), and negative for T cell markers CD3 and CD5 (Fig 2). Helicobacter pylori was not found. These findings were consistent with gastric MALToma. Whole-body positron-emission tomography scan did not show abnormal uptake in the stomach and the rest of body.
 
The patient was empirically treated with H pylori–eradication therapy (esomeprazole 20 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily for 1 week). She was then treated with four doses of rituximab (weekly for 4 weeks); this treatment was completed in June 2012. Repeated endoscopy and biopsy at 4 weeks after treatment showed a residual focus of MALToma. Radiotherapy (30 Gy) was subsequently given for improved local control in view of partial response to rituximab, which was completed in December 2012. Endoscopy performed 6 weeks after completion of radiotherapy showed complete response, ie, recovery of gastric pit pattern under ME (Fig 1b).
 

Figure 1. White light endoscopic images (upper) and magnified endoscopic images (lower)
(a) Magnified endoscopic image before treatment showing disappearance of the normal gastric pit pattern and appearance of irregular abnormal vessels (arrows). (b) Magnified endoscopic image after treatment showing recovery of gastric pits
 

Figure 2. Histopathology before treatment
(a) The atypical lymphoid cells form lymphoepithelial lesions. They show pale cytoplasm and mildly irregular hyperchromatic nuclei (H&E; original magnification, x 40). (b) The atypical lymphoid cells are diffusely positive for B cell marker CD20
 
Discussion
Gastric MALToma is uncommon and accounts for 1% to 5% of all gastric cancers. Isaacson and Wright1 first reported a low-grade gastric lymphoma in 1983. Lymphoid tissue is absent in the normal gastric mucosa. Helicobacter pylori is believed to play a causative role in the development of gastric MALToma.2 Gastric lymphoid tissue is acquired in response to local infection by H pylori, and there is a strong association between H pylori infection and gastric MALToma. Approximately 90% of gastric MALTomas are H pylori positive. Pathogenesis of gastric MALToma is a multistep process; H pylori infection causes chronic gastritis, which leads to immunological reaction with formation of lymphoid follicles and, subsequently, to genetic abnormalities and malignant transformation. Eradication of H pylori may lead to remission in 50% to 90% of cases.3 4 Most patients with gastric MALToma have an indolent clinical course; the 5-year overall survival after H pylori eradication has been reported to be 82% to 96%.5 6
 
The presentation of MALToma is variable. Patients may present with non-specific symptoms such as epigastric pain, vomiting, and weight loss. Endoscopy with biopsy is diagnostic but there is no endoscopic hallmark. The endoscopic appearance is also non-specific. It is difficult to differentiate gastric MALToma from gastric erosion or gastritis on conventional white light endoscopy. Diagnosis can be easily missed if multiple biopsies are not taken. Narrow-band imaging allows enhanced visualisation of microvascular and microsurface structures in the superficial part of the mucosa. The use of ME with NBI is useful for the diagnosis of early gastric cancer.7 Recently, retrospective studies have shown the characteristics of gastric MALToma on ME. Chiu et al8 reported abnormal spider-like vasculature and disappearance of gastric pits in nine patients with histological diagnoses of gastric MALToma, while Ono et al9 reported that non-structural areas with abnormal vessels were observed in 11 patients before treatment. The use of ME may help the endoscopist to take targeted biopsies from the abnormal areas.10
 
The histological criteria of gastric MALToma were established according to the World Health Organization criteria in 2001, which included (i) invasion of epithelial structures resulting in ‘lymphoepithelial lesions’; (ii) small lymphocytes, marginal zone cells, and/or monocytoid B cells; (iii) infiltration of diffuse, perifollicular, interfollicular, or even follicular type due to colonisation of reactive follicles.11
 
Surgery has been replaced by medical therapy in the management of gastric MALToma.12 It is generally recommended that H pylori–eradication therapy be the first-line therapy for H pylori–positive patients with localised gastric MALToma; eradication therapy should also be given to H pylori–negative patients, as there may be false-negative results.13 About 60% to 90% of patients with gastric MALToma achieve complete response after H pylori eradication.13 The presence of atrophic-like mucosa is a characteristic finding after treatment of gastric MALToma. Reported post-treatment ME findings include recovery of gastric pits and resolution of abnormal vascular pattern.8 It was demonstrated that the disappearance of non-structural areas with abnormal vessels was related to pathological remission.10
 
There is no consensus on treatment for those who fail to respond to eradication therapy. It is evident that patients with progressive disease or clinically evident relapse should undergo further treatment. Different treatment modalities include chemotherapy and radiotherapy. In a recently published multicentre cohort, high response rate to radiotherapy (94%) and chemotherapy (88%) was reported when used as second-line treatment in 82 non-responders and eight responders with relapse.14 Nine patients (out of 420 patients) showed transformation into diffuse large B cell lymphoma at a median follow-up period of 6 years.14 The management of patients with clinically partial remission is not well defined. A ‘watch and wait’ strategy has been advocated, and patients are followed up with interval endoscopies for evidence of progressive disease before considering oncological treatment.14 Rituximab, a chimeric antibody directed against CD20, is another therapeutic option. CD20 is a B cell–specific antigen expressed abundantly by the neoplastic cells of MALToma. The response rate has been reported to be around 70% in small series.15
 
In summary, patients with gastric MALToma present with non-specific symptoms, and there is no endoscopic hallmark. Endoscopy and biopsy are the gold standard for diagnosis. Magnifying endoscopy findings in MALToma include abnormal vessel patterns and disappearance of gastric pits; however, these findings have not been confirmed by large-scale prospective studies. Helicobacter pylori eradication is the first-line treatment. While the majority of patients respond to eradication therapy, those who fail to respond and develop progressive disease require oncological treatment. The management of partial responders is uncertain. Surveillance endoscopy is recommended in the follow-up of patients with MALToma in order to detect relapse.
 
Acknowledgement
We thank Dr Florence Loong (Department of Pathology, The University of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital) of providing the histopathology slides.
 
References
1. Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410-6. Crossref
2. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori–associated gastritis and primary B-cell gastric lymphoma. Lancet 1991;338:1175-6. Crossref
3. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993;342:575-7. Crossref
4. Zullo A, Hassan C, Cristofari F, et al. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol 2010;8:105-10. Crossref
5. Stathis A, Chini C, Bertoni F, et al. Long-term outcome following Helicobacter pylori eradication in a retrospective study of 105 patients with localized gastric marginal zone B-cell lymphoma of MALT type. Ann Oncol 2009;20:1086-93. Crossref
6. Zullo A, Hassan C, Andriani A, et al. Eradication therapy for Helicobacter pylori in patients with gastric MALT lymphoma: a pooled data analysis. Am J Gastroenterol 2009;104:1932-7. Crossref
7. Yao K, Oishi T, Matsui T, Yao T, Iwashita A. Novel magnified endoscopic findings of microvascular architecture in intramucosal gastric cancer. Gastrointest Endosc 2002;56:279-84. Crossref
8. Chiu PW, Wong TC, Teoh AY, et al. Recognition of changes in microvascular and microstructural patterns upon magnifying endoscopy predicted the presence of extranodal gastric MALToma. J Interv Gastroenterol 2012;2:3-7. Crossref
9. Ono S, Kato M, Ono Y, et al. Characteristics of magnified endoscopic images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue, including changes after treatment. Gastrointest Endosc 2008;68:624-31. Crossref
10. Ono S, Kato M, Ono Y, et al. Target biopsy using magnifying endoscopy in clinical management of gastric mucosa-associated lymphoid tissue lymphoma. J Gastroenterol Hepatol 2011;26:1133-8. Crossref
11. Isaacson PG, Muller-Hermelink HK, Paris MA, et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumors. Pathology and genetics of tumors of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001: 157-60.
12. Avilés A, Nambo MJ, Neri N, et al. The role of surgery in primary gastric lymphoma: results of a controlled clinical trial. Ann Surg 2004;240:44-50. Crossref
13. Fischbach W, Goebeler-Kolve ME, Dragosics B, Greiner A, Stolte M. Long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) following exclusive Helicobacter pylori eradication therapy: experience from a large prospective series. Gut 2004;53:34-7. Crossref
14. Nakamura S, Sugiyama T, Matsumoto T, et al. Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan. Gut 2012;61:507-13. Crossref
15. Martinelli G, Laszlo D, Ferreri AJ, et al. Clinical activity of rituximab in gastric marginal zone non-Hodgkin’s lymphoma resistant to or not eligible for anti–Helicobacter pylori therapy. J Clin Oncol 2005;23:1979-83. Crossref

Isolated spinal artery aneurysm: a rare culprit of subarachnoid haemorrhage

Hong Kong Med J 2015 Apr;21(2):179–82
DOI: 10.12809/hkmj144230
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Isolated spinal artery aneurysm: a rare culprit of subarachnoid haemorrhage
Tony HT Sung, MB, ChB, FRCR; Warren KW Leung, FHKCR, FHKAM (Radiology); Bill MH Lai, MB, BS, FRCR; Jennifer LS Khoo, FHKCR, FHKAM (Radiology)
Department of Radiology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
Corresponding author: Dr Tony HT Sung (sht557@ha.org.hk), (tttony100@gmail.com)
 Full paper in PDF
Abstract
Isolated spinal artery aneurysm is a rare lesion which could be accountable for spontaneous spinal subarachnoid haemorrhage. We describe the case of a 74-year-old man presenting with sudden onset of chest pain radiating to the neck and back, with subsequent headache and confusion. Initial computed tomography aortogram revealed incidental finding of subtle acute spinal subarachnoid haemorrhage. A set of computed tomography scans of the brain showed further acute intracranial subarachnoid haemorrhage with posterior predominance, small amount of intraventricular haemorrhage, and absence of intracranial vascular lesions. Subsequent magnetic resonance imaging demonstrated a thrombosed intradural spinal aneurysm with surrounding sentinel clot, which was trapped and excised during surgical exploration. High level of clinical alertness is required in order not to miss this rare but detrimental entity. Its relevant aetiopathological features and implications for clinical management are discussed.
 
 
[Abstract in Chinese]
 
Introduction
Aneurysmal subarachnoid haemorrhage (SAH) is an uncommon but fatal clinical event. The reported incidence in a recent international population-based epidemiological study ranged between 2 and 16 per 100 000 population,1 and the mortality rate ranged from 8% to 67%.2 Among all SAH cases, less than 1% are considered to originate from the spine.3 We present a case of isolated spinal artery aneurysm as a rare culprit of spinal and intracranial SAH to illustrate the diagnostic challenge, its relevant aetiopathological features, and implications for clinical management.
 
Case report
A 74-year-old Chinese man with a history of hypertension and ischaemic heart disease presented to the Accident and Emergency Department in February 2013 for sudden onset of chest pain radiating to the neck and back. Clinical examination and electrocardiogram on admission showed no evidence of myocardial infarction. Initial working diagnosis of acute aortic dissection was also excluded with urgent computed tomography (CT) aortogram. On retrospective analysis, subtle but definite hyperdensities within the thecal sac at upper thoracic levels were noted, suggestive of acute spinal SAH (Fig 1).
 

Figure 1. (a, b) Axial and (c) coronal reformatted images of the contrast computed tomography (CT) aortograms demonstrate subtle hyperdensities within the dural sac at upper thoracic levels, suggesting acute spinal subarachnoid haemorrhage (arrows). The cerebrospinal fluid in normal subjects should be hypodense, similar to water attenuation on CT. The spinal cord is outlined as a central elongated hypodense structure simulating a contrast myelogram
 
The patient developed gradual progressive headache and confusion requiring intubation on the fourth day of admission. Plain CT of the brain at that time revealed further diffuse acute SAH with predominance over the posterior aspect, as well as a small amount of acute intraventricular haemorrhage. No skull vault fracture was observed. Concurrent CT cerebral arteriogram and venogram did not demonstrate any aneurysms or venous sinus thrombosis. Subsequent digital subtraction angiogram (DSA) of cerebral arteries performed on the next day was unremarkable.
 
In view of posterior predominance of the intracranial SAH with negative cerebral angiograms, an urgent magnetic resonance imaging (MRI) of the brain and cervical spine (Fig 2) was performed for suspected subtle intracranial pathology and a spinal origin of SAH (observed rarely). A lobulated 8-mm intradural, extramedullary lesion with internal hypointense signal was seen at the T1/2 level abutting the lateral surface of the spinal cord. Trace contrast enhancement was noted within the lesion. Adjacent hyperintense signal and susceptibility artefacts within the dural sac were also observed, suggestive of sentinel clot formation. The spinal cord was displaced slightly by the lesion with associated mild cord oedema. Radiological differential diagnosis at this juncture included cavernoma, largely thrombosed spinal aneurysm, other exophytic haemorrhagic intramedullary tumour or slow-flow arteriovenous malformation (AVM).
 

Figure 2. (a) Axial T1-, (b) T2- and (c) post-contrast fat-suppressed T1-weighted magnetic resonance imaging (MRI) of the spine at T1 level shows a lobulated intradural, extramedullary hypointense lesion with subtle contrast enhancement (arrows) and surrounding hyperintense blood clot. The spinal cord (arrowheads) is displaced laterally with intramedullary T2-hyperintense oedema. Corresponding sagittal (d) T1-, (e) T2-, and (f) post-contrast fat-suppressed T1-weighted MRI of the spine also shows the lobulated intradural lesion and surrounding blood clot
 
Subsequent laminectomy and surgical exploration were performed for definitive diagnosis, which revealed a 7-mm saccular aneurysm surrounded by fibrin and an old haematoma from C7 to T2 level. The aneurysm arose from and was incorporated with the radicular artery at T1 level, showing internal partial thrombosis. The aneurysmal sac was trapped and carefully excised without jeopardising the rest of the arterial supply to the cord. The patient had good clinical recovery in postoperative rehabilitation with no further neurological complaints.
 
Discussion
Compared with more common causes of spinal SAH like AVM, dural arteriovenous fistula (dAVF) and haemorrhagic spinal cord tumours, spinal artery aneurysm remains a rare entity with a reported incidence of less than 1 in 3000 spinal angiograms, according to a large-scale review by Pia and Djindjian.4 Ever since the first case report on spinal aneurysm back in 1930,5 experience from various studies remains limited mainly to isolated case reports and case series with small sample sizes.
 
Spinal aneurysms are distinct from intracranial counterparts in several ways. First, they occur mostly along the course of their parent arteries which have a small calibre and are less affected by atherosclerosis.6 On the contrary, intracranial aneurysms are well known for their predilection for branching points of large-sized arteries which are more haemodynamically challenged. Second, spinal aneurysms tend to be small in size, whereas giant aneurysms are exclusively found intracranially, especially in patients with connective tissue disease. Third, many spinal aneurysms are found to be dissecting aneurysms in histology, which explains their fusiform shape and lack of a surgical neck.5 This hinders direct surgical clipping during treatment planning.
 
For aetiology, isolated spinal aneurysms, as in our case, are rare lesions. More commonly, they are associated with concomitant vascular lesions or occlusions which recruit the spinal artery as a collateral route for supplying and increasing local blood flow. This, in turn, imposes haemodynamic stress and induces aneurysm formation along the parent arteries. Reported associations include spinal cord AVM,7 dAVF,8 aortic coarctation,5 Moyamoya disease,9 and bilateral vertebral artery occlusion.10 Another group of spinal aneurysms is related to underlying vasculopathies. Common examples include collagen vascular disease such as rheumatoid arthritis,11 mycosis,12 and syphilis.5
 
The diagnosis of spinal artery aneurysm could be challenging and delayed due to its rarity. Most patients present with headache and backache related to aneurysmal rupture and SAH. Neurological deficits including paraparesis, quadriplegia, and cord compression have also been reported.13 As for investigations, MRI and DSA of the spine are sufficient to demonstrate the location and vascular anatomy of a spinal artery aneurysm on most occasions which, in turn, are valuable for treatment planning by neurosurgeons. The position of the aneurysm with respect to the spinal cord determines whether the anterior approach for transthoracic vertebrectomy or posterior laminectomy is most appropriate. In a large-scale literature review by Geibprasert et al,14 32 spinal artery aneurysms were studied, in which the majority (62.5%) arose from the anterior spinal artery. Origin from the radicular artery, as in our case, was scarcely seen (n=2). The authors also observed that posterior spinal artery aneurysms were predominantly isolated dissecting aneurysms. On the contrary, those from the anterior spinal artery are more diverse in aetiology, eg, related to candidiasis and connective tissue disease, which implies a non-surgical management approach with medical treatment for the underlying disorder. Even for isolated dissecting aneurysms from the anterior axis, surgical ligation or endovascular embolisation is still limited by increased risk of postoperative complications including spinal cord infarction due to possible compromise of the dominant arterial supply to the cord. Options of surgical approach include resection and wrapping of the aneurysmal sac, with possible microvascular reconstruction in individual cases. Rare cases of spontaneous complete healing of the dissecting aneurysm have been reported,12 but prompt treatment should not be delayed due to the associated severe complications.
 
Conclusion
Spinal artery aneurysms are rare culprits of SAH, with different morphological features of their intracranial counterparts. Associations with concurrent vascular lesions and vasculopathy are frequent, with a minority of cases being isolated in aetiology. Magnetic resonance imaging and DSA of the spine show their merit in delineating the location and vascular anatomy of a spinal artery aneurysm, which are key determinants in management planning. Surgical treatment should be prompt and performed cautiously in view of possible substantial neurological deficit when the arterial supply of the cord is jeopardised.
 
References
1. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009;8:355-69. Crossref
2. Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol 2009;8:635-42. Crossref
3. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet 2007;369:306-18. Crossref
4. Pia HW, Djindjian R. Spinal angiomas: advances in diagnosis and therapy. Berlin: Springer Verlag; 1987.
5. Rengachary SS, Duke DA, Tsai FY, Kragel PJ. Spinal arterial aneurysm: case report. Neurosurgery 1993;33:125-9; discussion 129-30. Crossref
6. Leech PJ, Stokes BA, ApSimon T, Harper C. Unruptured aneurysm of the anterior spinal artery presenting as paraparesis. Case report. J Neurosurg 1976;45:331-3. Crossref
7. Konan AV, Raymond J, Roy D. Transarterial embolization of aneurysms associated with spinal cord arteriovenous malformations. Report of four cases. J Neurosurg 1999;90(1 Suppl):148-54.
8. Malek AM, Halbach VV, Phatouros CC, et al. Spinal dural arteriovenous fistula with an associated feeding artery aneurysm: case report. Neurosurgery 1999;44:877-80. Crossref
9. Walz DM, Woldenberg RF, Setton A. Pseudoaneurysm of the anterior spinal artery in a patient with Moyamoya: an unusual cause of subarachnoid hemorrhage. AJNR Am J Neuroradiol 2006;27:1576-8.
10. Kawamura S, Yoshida T, Nonoyama Y, Yamada M, Suzuki A, Yasui N. Ruptured anterior spinal artery aneurysm: a case report. Surg Neurol 1999;51:608-12. Crossref
11. Toyota S, Wakayama A, Fujimoto Y, Sugiura S, Yoshimine T. Dissecting aneurysm of the radiculomedullary artery originating from extracranial vertebral artery dissection in a patient with rheumatoid cervical spine disease: an unusual cause of subarachnoid hemorrhage. Case report. J Neurosurg Spine 2007;7:660-3. Crossref
12. Berlis A, Scheufler KM, Schmahl C, Rauer S, Götz F, Schumacher M. Solitary spinal artery aneurysms as a rare source of spinal subarachnoid hemorrhage: potential etiology and treatment strategy. ANJR Am J Neuroradiol 2005;26:405-10.
13. Yahiro T, Hirakawa K, Iwaasa M, Tsugu H, Fukushima T, Utsunomiya H. Pseudoaneurysm of the thoracic radiculomedullary artery with subarachnoid hemorrhage. Case report. J Neurosurg 2004;100(3 Suppl Spine):312-5.
14. Geibprasert S, Krings T, Apitzsch J, Reinges MH, Nolte KW, Hans FJ. Subarachnoid hemorrhage following posterior spinal artery aneurysm. A case report and review of the literature. Interv Neuroradiol 2010;16:183-90.

Acquired factor V inhibitor in a patient receiving venous-venous extracorporeal membrane oxygenation for Legionella pneumonia

Hong Kong Med J 2015 Apr;21(2):175–8
DOI: 10.12809/hkmj134141
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Acquired factor V inhibitor in a patient receiving venous-venous extracorporeal membrane oxygenation for Legionella pneumonia
Anne KH Leung, FHKCA, FHKAM (Anaesthesiology)1; George WY Ng, FHKCP, FHKAM (Medicine)1; KC Sin, FHKCP, FHKAM (Medicine)1; SY Au, FHKCP, FHKAM (Medicine)1; KY Lai, FHKCP, FHKAM (Medicine)1; KL Lee, FHKCP, FHKAM (Medicine)2; KI Law, FHKCP, FHKAM (Medicine)2
1 Intensive Care Unit, Queen Elizabeth Hospital, Jordan, Hong Kong
2 Intensive Care Unit, United Christian Hospital, Kwun Tong, Hong Kong
 
Corresponding author: Dr Anne KH Leung (leungkha@ha.org.hk)
 
 Full paper in PDF
Abstract
We report a rare complication of factor V deficiency in a patient having Legionella pneumonia. This patient also had other complications like severe acute respiratory distress syndrome, acute kidney injury, and septic shock that required venous-venous extracorporeal membrane oxygenation support. This is the first reported case of acquired factor V deficiency in a patient receiving extracorporeal membrane oxygenation for Legionella pneumonia. With the combined use of intravenous immunoglobulin, rituximab and plasma exchange, we achieved rapid clearance of the factor V inhibitor within 1 week so as to allow safe decannulation of extracorporeal membrane oxygenation.
 
 
[Abstract in Chinese]
Case report
This was the case of a 53-year-old lorry driver with a history of pulmonary tuberculosis and chronic smoking, who presented in December 2012 with fever, cough, and sputum. Chest X-ray (CXR) showed left lower zone consolidation; the patient was diagnosed to have community-acquired pneumonia which was treated with ceftriaxone and azithromycin. Two days later, both the renal and liver functions worsened with elevation of serum urea level to 23.2 mmol/L (reference range [RR], 8-8.1 mmol/L), creatinine level to 493 µmol/L (RR, 62-106 µmol/L), aspartate transaminase level to 300 IU/L (reference level [RL], <40 IU/L), and alanine transaminase level up to 94 IU/L (RL, <41 IU/L). There was severe rhabdomyolysis with increased serum creatine kinase levels to 11 010 IU/L (RR, 39-308 IU/L). Urine tested positive for Legionella antigen. Antibiotic was changed to piperacillin-tazobactam and azithromycin. The patient developed respiratory failure the next day and was admitted to the intensive care unit (ICU) for ventilator support. His condition gradually stabilised over the next 10 days and sputum culture showed growth of Legionella pneumophila serogroup 1.
 
By day 11 in the ICU, he developed secondary deterioration with rapid progression of pulmonary infiltrates on CXR, septic shock, and acute kidney injury. Sputum culture after ICU admission showed growth of Pseudomonas aeruginosa and Corynebacterium species. Antibiotic was changed to meropenem and levofloxacin. By day 12, his oxygenation could not be maintained with conventional ventilation and the Murray score was 3.5. The patient was referred for extracorporeal membrane oxygenation (ECMO) support.
 
As his condition was unstable for transfer to the ECMO centre, venous-venous ECMO (VV-ECMO) was initiated at the referring hospital by percutaneous placement of two ECMO cannulas (23F and 19F) into the femoral vein and right internal jugular vein, respectively. The ECMO circuitry consisted of the Quadrox-i hollow-fibre oxygenator and Cardiohelp centrifugal pump (Maquet Cardiopulmonary AG, Germany). The circuit flow was started at 3.2 to 2.8 L/min during the first ECMO day, and then subsequently increased to 4.0 to 5.0 L/min to achieve PaO2 of 8 to 10 kPa. The ventilator setting was then decreased to peak airway pressure of <25 cm H2O, positive end–expiratory pressure of 10 cm H2O and FiO2 of 0.4. Heparin was started according to protocol with bolus 70 unit/kg after cannulation, followed by continuous infusion at 10 unit/kg/h to achieve an activated clotting time (ACT) of 200 to 220 seconds. The coagulation profile, ACT, renal function, and arterial blood gas were monitored every 4 hours.
 
Before initiation of VV-ECMO, the baseline international normalised ratio (INR) was 1.1 and activated partial thromboplastin time (APTT) was 33.7 seconds (RR, 28-34.6 seconds). A full blood count showed a haemoglobin concentration of 68 g/L, white cell count of 16 x 109 /L, and a platelet count of 169 x 109 /L. Continuous veno-venous haemofiltration (CVVH) was started for renal support. By day 4 of ECMO, INR started to prolong (1.61) and gradually increased to 2.32 and 3.36 over the next 2 days. Heparin was stopped, and vitamin K 10 mg and repeated fresh frozen plasma (FFP) transfusions ranging from 8 to 14 units per day were given. Throughout this period, the fibrinogen level remained normal at 4.44 g/L (RR, 2-4.5 g/L) and platelet count was greater than 100 x 109 /L. Liver function and ammonia level were normal. The coagulopathy could not be corrected by FFP. A haematologist was consulted and further tests were arranged. By day 8, the INR peaked at 4.06, and APTT increased to 115 seconds with slight prolongation of thrombin time (TT) to 15.3 seconds (TT control = 14.4 seconds). Coagulation factor assay showed factor V of 1% (RR, 50-200%) while factor VII, VIII, IX, X, XI and XII levels were within reference intervals. Factor V inhibitor assay showed levels increased up to 6 Bethesda units. The diagnosis of acquired factor V inhibitors was made.
 
In the presence of significantly high levels of factor V inhibitor and risk of spontaneous intracranial bleed, intravenous immunoglobulin (IVIG) at 60 g/day was given for 2 days. The patient’s INR decreased from 3.96 to 2.56 and APTT decreased from 105.4 to 55.3 seconds. The workup for immune markers including C3, C4, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic and perinuclear neutrophil antibodies, anti-extractable nuclear antigen, and anti-cardiolipin antibodies was negative. The tumour markers were negative as well. The patient received no surgical procedure. He had been put on four antibiotics after ECMO including azithromycin, meropenem, fluconazole, and linezolid. By day 4 of ECMO, fluconazole was replaced with anidulafungin for fungal cover.
 
Despite IVIG, the patient developed significant clinical bleeding with full-stream haematuria and bronchoscopy showed extensive blood clots in the left lower lobe. At the same time, his pulmonary mechanics and CXR started to improve after 10 days of ECMO support and he appeared ready to be weaned off from ECMO. It was decided to give him one dose of rituximab 700 mg on day 11 of ECMO. His INR decreased to 1.29 and APTT to 33.6 seconds over the next 2 days (Figs 1 and 2). The patient was successfully decannulated on day 13 of ECMO. The haematuria remained severe and required continuous bladder irrigation. Citrate CVVH was started for renal support. One session of plasma exchange was given after decannulation. The haematuria eventually stopped by day 16. Two days later, urinary output returned to normal and the patient was successfully extubated. By day 19, the patient was transferred back to the parent hospital with INR of 1.02, APTT of 30.4 seconds, and factor V assay of 173%. The patient was discharged 3 weeks later and his coagulation profile remained normal without further eradication therapy. At the time of discharge, the patient was able to walk with the help of a walking stick, could perform activities of daily living independently, and was dialysis-independent.
 

Figure 1. INR and APTT profiles of the patient during the 19-day stay at ECMO centre
 

Figure 2. Detailed INR and APTT profiles of the patient from day 8 to day 12
 
Discussion
Factor V deficiency: causes, clinical course, laboratory finding, treatment, and outcome
Factor V is a plasma cofactor that activates prothrombin to thrombin, thus, affecting the common final pathway of the coagulation cascade. About 20% of the circulating factor V is found within platelet α granules.1 The first reported case of congenital factor V deficiency was from Germany in 1955,2 and to date, about 200 reported cases have been reported.1 Congenital factor V deficiency is a rare autosomal recessive disease with a prevalence of 1 in 1 000 000.1 In acquired cases, it is related to the presence of factor V inhibitor.3 In one case series of 78 patients, the commonest cause was the use of antibiotics (42%), including β-lactam antibiotics, aminoglycosides, cephalosporins, tetracyclines, and quinolones. The next common cause was surgical procedure (31%) with exposure to bovine thrombin, which is a topical haemostatic agent widely used in cardiovascular or neurosurgical procedures.4 Infection, cancer, and autoimmune disease were present in 23%, 22%, and 13% of the cases, respectively. About 16 (21%) cases had no identifiable causes.3
 
The median age of presentation was 69 years, with a tendency for male predominance.3 Overall, 81% of cases had bleeding, and the mucous membranes of most frequently reported sites including gastro-intestinal tract, genito-urinary tract, and the airway were noted in up to 62% of cases.3 Cerebral haemorrhage occurred in only 8% of cases, but was associated with 50% mortality.3 Some cases were associated with thrombotic complications rather than haemorrhage.5
 
Laboratory findings included a prolonged prothrombin time and APTT that failed to be corrected by mixing studies. Thrombin time was usually normal unless there is presence of thrombin inhibitor. Bethesda assay is used to detect and quantify the presence of inhibitors. One Bethesda unit is defined as the amount that decreases factor V concentration by 50%.4 5 Bleeding correlated with factor V activity with median factor V activity being 1% in bleeders and 3% in non-bleeders.3
 
Treatment mainly consists of controlling bleeding and eradication of the autoantibody. Daily infusion of 15 to 20 mL/kg of FFP is usually sufficient.1 In refractory cases, recombinant factor VIIa, activated prothrombin complex concentrate, and platelet transfusion are therapeutic options.1 3 6 Plasmapheresis and immunoadsorption can rapidly reduce antibody titres. For immunosuppression, corticosteroids and cyclophosphamide have shown a success rate of 63%.3 Use of high-dose IVIG and anti-20 monoclonal antibody rituximab were associated with rapidly increasing factor V activity, although results were conflicting.3 6
 
The alloantibody against factor V was polyclonal immunoglobulin G7 and it disappeared in the majority of cases (69%) either after eradiation therapy (43/78 patients) or spontaneously (12/78 patients).3 7 For those patients who survived, factor V inhibitor persisted for a mean period of 5.1 months8 (range, <1 month to several years).6 7 For those related to bovine thrombin, the inhibitor emerged after a mean of 8.3 days of exposure and persisted for a shorter time of 2.3 months.8 Overall, 72% of patients with acquired factor V inhibitors suffered bleeding complications, with 17% of those being fatal.8 For those with acquired factor V deficiency with a known cause like bovine thrombin–induced factor V inhibitor, bleeding was less common (33%) and was associated with better prognosis and lower fatality (6%).8 The highest mortality was found in patients with autoimmune disorder (30%) or cancer (24%).3
 
Use of extracorporeal membrane oxygenation for Legionella pneumonia
Use of ECMO has been reported locally for treating influenza H1N1 with good outcome.9 Use of ECMO in Legionella pneumonia with acute respiratory distress syndrome has been reported,10 11 12 with survival rate ranging from 67% to 84% in the UK series.10 11 Acute renal failure was a common complication of legionellosis with 53.7% requiring renal replacement therapy. The prognosis for this subgroup of patients was poor with only 33% (vs 70% in those without acute renal failure) surviving to decannulation and mortality increasing from 15% to 53%.10 Major bleeding complications reported in these series included intra-abdominal bleeding, cardiac tamponade, chest drain–related haemorrhage, and gastro-intestinal and intracranial bleeding.9 10 11
 
This is the first reported case of acquired factor V inhibition in a patient put on VV-ECMO for Legionella pneumonia. Although our patient had acute renal failure and ECMO was instituted late in his course of illness (13 days after intubation), he responded favourably. The cause of the acquired factor V inhibition was uncertain. It may be related to the underlying infection, use of antibiotics, or be idiopathic in nature. The coagulopathy was not corrected by FFP transfusion and the patient had symptomatic bleeding with haematuria and pulmonary haemorrhage despite IVIG therapy. Although we could wait for the natural disappearance of the factor V inhibitor, it might prolong weaning from ECMO and increase the risk of fatal complications like intracranial bleeding. Yet, too early prescription of rituximab as in this patient might mask the effect of IVIG. Lastly, there was a remote possibility that the observed decrease in INR and APTT could be due to natural progression of the underlying disease rather than a treatment effect as only 15% of patients have spontaneous resolution of disease and the factor V inhibitors can persist in the body for months.3 6 7 In one case report, INR remained elevated for 10 days despite immunosuppressive therapy and returned to normal over the next 2 weeks.4 The need for ECMO decannulation and presence of active symptoms made correction of coagulopathy more imminent. The use of multimodal therapy including IVIG, rituximab, and plasma exchange in this patient successfully halted the progress of the factor V inhibitor and allowed safe decannulation within a period of 1 week.
 
References
1. Huang JN, Koerper MA. Factor V deficiency: a concise review. Haemophilia 2008;14:1164-9. Crossref
2. Horder MH. Isolated factor V deficiency caused by a specific inhibitor [in German]. Acta Haematol 1955;13:235-41.
3. Franchini M, Lippi G. Acquired factor V inhibitors: a systematic review. J Thromb Thrombolysis 2011;31:449-57. Crossref
4. Morris CJ, Curry N. Acquired factor V inhibitor in a critically ill patient. Anaesthesia 2009;64:1014-7. Crossref
5. Crookston K, Rosenbaum L, Gober-Wilcox J. Coagulation. Acquired bleeding disorders. Factor V inhibitor. Available from: http://www.pathologyoutlines.com/topic/coagulationfactorVinhibitor.html. Accessed Nov 2013.
6. Lu L, Liu Y, Wei J, Zhang L, Zhang L, Yang R. Acquired inhibitor of factor V: first report in China and literature review. Haemophilia 2004;10:661-4. Crossref
7. van Spronsen DJ, Oosting JD, Hoffmann JJ, Breed WP. Factor V inhibitor associated with cold agglutinin disease. Ann Hematol 1998;76:49-50. Crossref
8. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion 2002;42:18-26. Crossref
9. Chan KK, Lee KL, Lam PK, Law KI, Joynt GM, Yan WW. Hong Kong’s experience on the use of extracorporeal membrane oxygenation for the treatment of influenza A (H1N1). Hong Kong Med J 2010;16:447-54.
10. Bryner B, Miskulin J, Smith C, et al. Extracorporeal life support for acute respiratory distress syndrome due to severe Legionella pneumonia. Perfusion 2014;29:39-43. Crossref
11. Noah MA, Ramachandra G, Hickey MM, et al. Extracorporeal membrane oxygenation and severe acute respiratory distress secondary to Legionella: 10 year experience. ASAIO J 2013;59:328-30.
12. Harris DJ, Duke GJ, McMillan J. Extracorporeal membrane oxygenation for Legionnaires disease: a case report. Crit Care Resusc 2002;4:28-30.
 

Unexplained childhood anaemia: idiopathic pulmonary hemosiderosis

Hong Kong Med J 2015 Apr;21(2):172–4
DOI: 10.12809/hkmj144237
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Unexplained childhood anaemia: idiopathic pulmonary hemosiderosis
KK Siu, MB, ChB, MRCPCH1; Rever Li, MB, ChB, FHKAM (Paediatrics)2; SY Lam, MB, BS, FHKAM (Paediatrics)2
1 Department of Paediatrics, Kwong Wah Hospital, Yaumatei, Hong Kong
2 Department of Paediatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong
 
Corresponding author: Dr KK Siu (skk053@ha.org.hk)
 
 Full paper in PDF
Abstract
This report demonstrates pulmonary haemorrhage as a differential cause of anaemia. Idiopathic pulmonary hemosiderosis is a rare disease in children; it is classically described as a triad of haemoptysis, pulmonary infiltrates on chest radiograph, and iron-deficiency anaemia. However, anaemia may be the only presenting feature of idiopathic pulmonary hemosiderosis in children due to occult pulmonary haemorrhage. In addition, the serum ferritin is falsely high in idiopathic pulmonary hemosiderosis which increases the diagnostic difficulty. We recommend that pulmonary haemorrhage be suspected in any child presenting with iron-deficiency anaemia and persistent bilateral pulmonary infiltrates.
 
 
[Abstract in Chinese]
Case report
We report the case of a 5-year-old boy, who presented with recurrent episodes of unexplained iron-deficiency anaemia in February 2010 since the age of 27 months. Serial chest X-rays (CXRs) showed bilateral reticulonodular haziness. Bronchoalveolar lavage and lung biopsy confirmed the diagnosis of idiopathic pulmonary hemosiderosis (IPH).
 
The patient first presented at 27 months of age in Mainland China with malaise, loss of appetite, and shortness of breath for 10 days. He did not have fever, cough, or haemoptysis. He received two doses of H1N1 vaccination before pallor was noted. There was no history of drug or herb intake.
 
The presenting haemoglobin (Hb) level was 65 g/L (reference range [RR], 115-145 g/L), mean corpuscular volume (MCV) 84.4 fL (RR, 76-90 fL), mean corpuscular haemoglobin (MCH) level 25.8 pg (RR, 25-31 pg), and reticulocyte count 10.4% (reference level [RL], <2%). White cell count and platelet count were unremarkable. Blood smear showed moderate anisopoikilocytosis with polychromasia. Bone marrow aspiration and trephine biopsy revealed active marrow with erythroid preponderance.
 
Other investigations were performed for anaemia. Serum lactate dehydrogenase (LDH) level was elevated to 980 U/L (RL, <615 U/L). Haptoglobin level was reduced (<0.09 g/L; RR, 0.3-2.7 g/L). Direct Coombs test was negative. Bilirubin was normal. Urine for bilirubin and urobilinogen was negative. Haemoglobin pattern, serum vitamin B12, and G6PD activity were unremarkable. Serum ferritin level was 137 pmol/L (RR, 45-449 pmol/L). Antinuclear antibody assay was negative. Flow cytometry showed normal expression of CD55 and CD59 which ruled out paroxysmal nocturnal haemoglobinuria. Donath-Landsteiner antibody assay was negative, which excluded the diagnosis of paroxysmal cold haemoglobinuria.
 
Blood work for viral infection including antibodies to parvovirus, Epstein-Barr virus (EBV), mycoplasma, and viral titres was unremarkable.
 
Screening for blood loss was negative. Stool for occult blood and urine for Hb were negative. Red blood cell scan showed no evidence of haemorrhage.
 
Blood transfusion was given to correct the anaemia. Microcytic hypochromic anaemia was noted at 2 months after presentation. Haemoglobin level was 54 g/L. Mean corpuscular volume dropped from 84.4 fL to 68 fL. Mean corpuscular haemoglobin level was 21.3 pg. Iron profile showed a low serum iron level of 3 µmol/L (RR, 5-20 µmol/L), elevated total iron-binding capacity (TIBC) of 70 µmol/L (RR, 37-68 µmol/L), and iron saturation of 4% (RR, 20-55%). However, the serum ferritin level was normal at 220 pmol/L (RR, 45-449 pmol/L). Iron supplement was started as a therapeutic trial for suspected iron-deficiency anaemia.
 
His Hb level remained stable in the next 2 years. However, in the subsequent 8 months, there were three intermittent episodes of anaemia (lowest Hb level, 60 g/L). The anaemia occurred with fever and cough which were considered symptoms of pneumonia and upper respiratory tract infection. There was no history of haemoptysis.
 
At 36 months after the presentation, he was admitted again for pallor, fatigue, and fever. This time, he needed oxygen therapy. Chest was clear with mild subcostal insucking. Hepatomegaly of 4 cm below the costal margin was noted. Chest X-ray showed bilateral reticulonodular haziness (Fig 1). Haemoglobin level was 61 g/L. Both MCV (78 fL) and MCH level (25 pg) were in the lower normal limits. The serum ferritin level was 879 pmol/L. A diagnosis of pneumonia was made; he was started on oral co-amoxiclav (amoxicillin and clavulanic acid) and azithromycin and given blood transfusion. Fever subsided and oxygen was weaned off. Ultrasonography of abdomen performed 1 month later showed no hepatomegaly; mild hepatic coarsening was suggestive of parenchymal disease. Liver function tests were normal all along. However, the patient tested positive for EBV immunoglobulin (Ig) M antibodies. Thus, he was diagnosed to have pneumonia with EBV infection.
 

Figure 1. A chest X-ray showing bilateral reticulonodular haziness
 
Review of old CXRs showed similar reticulonodular shadows. In view of his history of recurrent iron-deficiency anaemia and CXR findings, pulmonary hemosiderosis was suspected. Flexible bronchoscopy was performed; bronchoscopic lavage over left lingular and right middle lobe showed blood-stained fluid. Bronchoalveolar lavage yielded abundant hemosiderin-laden macrophages (HLM index, 92%). High-resolution computed tomography of thorax showed extensive ground glass opacities and reticular shadows, suggestive of interstitial lung disease. Diffuse visceral pleural brownish deposits were noted over the entire left lung on video-assisted thoracoscopy. Lung biopsy was performed to rule out systemic disorders with pulmonary capillaritis, which could cause diffuse alveolar haemorrhage (DAH). These included Goodpasture’s syndrome, IgA nephropathy, Wegener’s granulomatosis, systemic lupus erythematosus, and antiphospholipid syndrome. Biopsy of lung tissue showed numerous HLM. There was no evidence of capillaritis or vasculitis. Absence of fibrosis and negative exposure history also excluded hypersensitivity pneumonitis. Immunostaining for IgG, IgM, and IgA was negative. The overall picture was compatible with pulmonary hemosiderosis.
 
Further blood investigations were performed to exclude systemic causes of pulmonary haemorrhage as stated above. Antiglomerular basement membrane antibodies, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, antinuclear antibodies, anti-extractable nuclear antibodies, and anti-cardiolipin IgG antibodies were not detected. Furthermore, the patient was negative for anti-transglutaminase antibody for coeliac disease. He tested weakly positive for IgE antibodies against cow’s milk. Immunoglobulin pattern was unremarkable apart from mildly raised IgA antibody level at 2.28 g/L (range, 0.5-1.92 g/L). Renal function and urinalysis were normal.
 
A diagnosis of IPH was made based on the above findings. Oral prednisolone was started after the diagnosis for disease control. Chest X-ray performed after 3 months of prednisolone showed improvement in reticulonodular densities (Fig 2). We plan to monitor the disease with clinical symptoms, Hb levels, LDH levels, CXRs, and spirometry.
 

Figure 2. A chest X-ray performed after 3 months of prednisolone therapy showing improvement in reticulonodular densities
 
Discussion
Idiopathic pulmonary hemosiderosis is a rare disease in children with an unknown aetiology. The estimated yearly incidence among Swedish children from 1960 through 1979 was 0.24 per 1 000 000 children.1 A retrospective review of records from a tertiary paediatric hospital in northern Taiwan noted five cases over 25 years.2 Patients classically presented with a triad of recurrent or chronic pulmonary symptoms (cough, dyspnoea, wheeze, haemoptysis), pulmonary infiltrates on CXR, and iron-deficiency anaemia. Our patient had only anaemia without obvious underlying causes. Subsequent CXR changes led to the suspicion of IPH.
 
Serum ferritin has been traditionally taken as a reliable surrogate marker of body iron stores. Hypoferritinaemia is commonly used as a diagnostic marker for iron deficiency.3 However, as it is an acute-phase reactant, abnormally raised serum ferritin level may be seen during acute infection or liver disease even in the presence of iron deficiency.4 In IPH, iron study usually shows low serum iron with low iron saturation, and microcytosis and hypochromia in the blood picture. However, plasma ferritin level can be normal or elevated in IPH because of alveolar synthesis and release into the circulation and does not reflect the iron deposits in the body.5 This makes the diagnosis of iron-deficiency anaemia in IPH difficult. We recommend the use of serum iron and transferrin saturation (serum iron/TIBC) instead to evaluate suspected iron-deficiency anaemia.4
 
Diagnosis of IPH is based on exclusion of other causes of intrapulmonary haemorrhage and systemic diseases. In the absence of systemic disease, findings of HLM in bronchoscopic lavage or gastric aspirate/sputum along with chronic pulmonary symptoms lead to a diagnosis of IPH. Lung biopsy is the gold standard for diagnosis. We performed lung biopsy to exclude pulmonary capillaritis, which is one of the causes of DAH. Pulmonary capillaritis is a small-vessel vasculitis, which can occur as an isolated condition or in association with multiple systemic vasculitides. Isolated DAH without identifiable causation or associated disease is referred to as IPH.6
 
Daily oral corticosteroids or weekly intravenous pulse methylprednisolone is commonly used in the induction treatment of IPH. Other immunosuppressive agents such as azathioprine, cyclophosphamide, and hydroxychloroquine have also been used alone or in combination with oral corticosteroids.7 8 9 10 11 Low-dose oral corticosteroids, azathioprine, or methotrexate are used in maintenance phase. As there is lack of large patient series and inadequate follow-up in previous studies, the prognosis of IPH remains unclear. However, aggressive treatment with the use of corticosteroids and immunosuppressive agents are associated with a prolonged survival and improved prognosis.12 Long-term low-dose corticosteroid therapy was also reported to result in a milder disease course and prevent bleeding crisis.13
 
In conclusion, iron-deficiency anaemia results from poor dietary intake of iron in infants and toddlers. However, every child older than 24 months presenting with iron-deficiency anaemia should be evaluated for chronic blood loss. In this report, we have illustrated that anaemia without any respiratory symptoms can be the sole presenting feature of IPH, preceding other signs and symptoms, especially in young children. Haemoptysis may not be present in young children with IPH, as they tend to swallow their sputum. We recommend that when children present with unexplained anaemia and bilateral lung infiltrations, pulmonary haemorrhage should be suspected.
 
References
1. Kjellman B, Elinder G, Garwicz S, Svan H. Idiopathic pulmonary haemosiderosis in Swedish children. Acta Paediatr Scand 1984;73:584-8. Crossref
2. Yao TC, Hung IJ, Wong KS, Huang JL, Niu CK. Idiopathic pulmonary haemosiderosis: an Oriental experience. J Paediatr Child Health 2003;39:27-30. Crossref
3. Rybo E. Diagnosis of iron deficiency. Scand J Haematol Suppl 1985;43:5-39.
4. Li CH, Lee AC, Mak TW, Szeto SC. Transferrin saturation for the diagnosis of iron deficiency in febrile anaemic children. Hong Kong Pract 2003;25:363-6.
5. Ioachimescu OC, Sieber S, Kotch A. Idiopathic pulmonary haemosiderosis revisited. Eur Respir J 2004;24:162-70. Crossref
6. Fullmer JJ, Langston C, Dishop MK, Fan LL. Pulmonary capillaritis in children: a review of eight cases with comparison to other alveolar hemorrhage syndromes. J Pediatr 2005;146:376-81. Crossref
7. Milman N, Pedersen FM. Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis. Respir Med 1998;92:902-7. Crossref
8. Rossi GA, Balzano E, Battistini E, et al. Long-term prednisolone and azathioprine treatment of a patient with idiopathic pulmonary hemosiderosis. Pediatr Pulmonol 1992;13:176-80. Crossref
9. Colombo JL, Stolz SM. Treatment of life-threatening primary pulmonary hemosiderosis with cyclophosphamide. Chest 1992;102:959-60. Crossref
10. Zaki M, al Saleh Q, al Mutari G. Effectiveness of chloroquine therapy in idiopathic pulmonary hemosiderosis. Pediatr Pulmonol 1995;20:125-6. Crossref
11. Bush A, Sheppard MN, Warner JO. Chloroquine in idiopathic pulmonary haemosiderosis. Arch Dis Child 1992;67:625-7. Crossref
12. Saeed MM, Woo MS, MacLaughlin EF, Margetis MF, Keens TG. Prognosis in pediatric idiopathic pulmonary hemosiderosis. Chest 1999;116:721-5. Crossref
13. Kiper N, Göçmen A, Ozçelik U, Dilber E, Anadol D. Long-term clinical course of patients with idiopathic pulmonary hemosiderosis (1979-1994): prolonged survival with low-dose corticosteroid therapy. Pediatr Pulmonol 1999;27:180-4. Crossref
 

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