In August 2014, an 18-year-old boy with no prior history of coronary or cardiac disease presented to our tertiary cardiovascular and thoracic surgery hospital in Turkey with crushing substernal chest pain, nausea, and vomiting that had persisted for 1 hour. He had started work as a barman at a beach club 3 months earlier and denied any use of off-label drugs. His first electrocardiography (ECG) was normal with sinus rhythm (heart rate, 90 beats/min; Fig 1a). The patient, however, was tachypnoeic and reported a heavy squeezing chest discomfort. On physical examination, the pain was not relieved by position change and increased continuously. Blood pressure was 142/75 mm Hg and pulse oximetry showed oxygen saturation to be 94%. Chest auscultation was normal, as was chest X-ray. Cardiomegaly and pneumothorax were absent and the mediastinum was not widened.

Smoking was the only risk factor for developing coronary artery disease in this young patient. Hypertension, diabetes mellitus, hyperlipidaemia, family history of heart disease, and obesity were absent as risk factors for coronary artery disease.

The patient was thought to have myocarditis and ibuprofen was prescribed for symptom relief. The pain worsened, however, and ECG showed widened QRS complexes (right bundle branch block pattern in precordial derivations) with a rate of 112 beats/min (Fig 1b). The ECG was interpreted as idioventricular rhythm. Bedside transthoracic echocardiography was performed and left ventricular anterior wall hypokinesis with 40% ejection fraction was observed. Clopidogrel and acetylsalicylic acid were started and immediate coronary angiography (CAG) was performed to identify the cause. A significant stenosis of the mid-segment of the left anterior descending (LAD) artery with a fresh thrombus image was present with distal TIMI-3 flow (Thrombolysis In Myocardial Infarction grade 3, which implies normal flow that fills the distal coronary bed completely) [Fig 2a]. Right coronary artery and left circumflex artery were normal. Since the patient’s haemodynamic parameters were stable with TIMI-3 distal blood flow in the LAD, conservative treatment with intravenous glycoprotein 2b/3a (GP-2b3a) inhibitor was prescribed. After successful infusion of GP-2b3a without any complications, control CAG was performed (Fig 2b). Complete dissolution of thrombus was observed and left ventricular anterior hypokinesis was reversed.

The patient’s laboratory findings were all within normal range except markers of myocardial damage. Troponin I level was 24 µg/L. Platelet count and liver function tests were normal, as was clotting panel. The patient’s blood was screened for factor V Leiden mutation, prothrombin gene mutation, MTHFR gene mutation, protein C activity, protein S activity, plasminogen activator inhibitor–1 activity, homocysteine levels, and anti-cardiolipin antibodies. No secondary aetiology was evident that could account for such thrombus formation in an 18-year-old boy so he was further questioned about drug use. This time he admitted the use of marijuana 1 hour prior to the onset of intense chest pain.

Acute myocardial infarction (AMI) is the leading cause of death in North America and Europe.1 Despite this, AMI in an 18-year-old teenage boy is very rare. In our case the possible causes of thrombophilia were excluded and smoking of cannabis was thought to be the main cause of AMI.

Recent cannabis use is associated with acute coronary syndrome and can lead to severe cardiovascular problems and sudden death, not only in people at increased cardiovascular risk but also in young people without any medical history or risk factors.2 The effects of cannabinoids are primarily mediated by the activation of cannabinoid receptors that are present in a variety of tissues including the brain (basal ganglia, pars reticulata of the substantia nigra, entopeduncular nucleus, globus pallidus, putamen, cerebellum, hippocampus, and cerebral cortex) and cells of the immune system, spleen, blood vessels, and the heart.3

The pharmacological effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2 that are widely distributed in the cardiovascular system, have been well described. A dose-dependent increase in heart rate up to 100% of basal rate occurs 10 to 30 minutes after beginning to smoke.4 Most users experience an increase in blood pressure especially while supine4 although postural hypotension after smoking marijuana is common. Tolerance to this drug can occur with frequent repeated use.5 Another harmful effect of smoked marijuana is associated with an increase in carboxyhaemoglobin, resulting in decreased oxygen-carrying capacity6 and subsequent demand-supply mismatch by decreasing oxygen transportation to the heart. This mechanism is suggested to underlie atherosclerotic stable coronary disease and concomitant cannabinoid use. Nonetheless in our case, the patient was too young and the lesion appearance on CAG was suggestive of a small plaque rupture with superimposed thrombus formation rather than stable atherosclerotic disease. Acute myocardial infarction associated with cannabinoid use and with normal coronary artery has been reported in the literature. Ours is an interesting case report associated with cannabinoid inhalation and superimposed thrombus formation detected by CAG. In our patient, implantation of a stent in the LAD artery was not an option because the lesion was thought to be thrombotic. Dissolution of the thrombus was achieved with GP-2b3a infusion.

Clinicians are reminded of this very rare aetiology of acute coronary syndrome and its management among young patients. Bearing in mind the increasing use of drugs such as marijuana and other synthetic cannabinoids among young people, management of associated cardiac problems is vital. A CAG should be performed whenever drug abuse is suspected in any patient who presents with chest pain. If a thrombotic lesion is detected on CAG, infusion of GP-2b3a may dissolve the thrombus.

1. Griffin BP, editor. Manual of cardiovascular medicine. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2009: 1.

2. Casier I, Vanduynhoven P, Haine S, Vrints C, Jorens PG. Is recent cannabis use associated with acute coronary syndromes? An illustrative case series. Acta Cardiol 2014;69:131-6.

3. Járai Z, Wagner JA, Varga K, et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 1999;96:14136-41. Crossref

4. Johnson S, Domino EF. Some cardiovascular effects of marihuana smoking in normal volunteers. Clin Pharmacol Ther 1971;12:762-8. Crossref

5. Benowitz NL, Jones RT. Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion. Clin Pharmacol Ther 1975;18:287-97. Crossref

6. Aronow WS, Cassidy J. Effect of marihuana and placebo-marihuana smoking on angina pectoris. N Engl J Med 1974;291:65-7. Crossref

A 68-year-old male had end-stage renal failure due to diabetes mellitus. He underwent Tenckhoff catheter insertion in 2013 for continuous ambulatory peritoneal dialysis (CAPD). The catheter was flushed regularly once a week and was functional in the first 2 months following insertion.

The catheter became blocked 2 months following insertion after an episode of CAPD peritonitis. Peritoneal dialysate showed scanty growth of Stenotrophomonas (Xanthomonas) maltophilia. Kidney, ureter, and bladder X-ray (KUB) was ordered to identify catheter tip position that was subsequently revealed to be in the central part of the pelvic cavity (Fig 1a). The cause of blockage was suspected to be omental wrap. Omentectomy was planned and the Tenckhoff catheter was left in situ; CAPD peritonitis was successfully treated with antibiotics and the patient was discharged. The peritoneal membrane was rested for 2 weeks and the patient maintained on temporary twice-weekly haemodialysis.

The patient was admitted to Tuen Mun Hospital again in early 2014 because of fall. Computed tomographic (CT) brain revealed a significant left acute subdural haemorrhage. Urgent craniotomy with clot evacuation was performed. At that time, abdominal X-ray demonstrated inferior migration of the catheter tip with loss of coiling of the distal tip (Fig 1b). A few days later, the tip of Tenckhoff catheter was noticed in the anus of the patient. Follow-up KUB confirmed the clinical finding (Fig 1c).

The patient had no symptoms or signs of acute peritonitis. Contrast-enhanced CT abdomen and pelvis confirmed perforation of the Tenckhoff catheter through the sigmoid colon with the tip in the anus (Fig 1d).

The contrast-enhanced CT demonstrated Tenckhoff catheter perforation through the sigmoid colon (Fig 2a) with soft-tissue fibrosis around the catheter at the site of the perforation (Fig 2b). There was no ascites or inflammatory fluid collection. Contrast enema showed no evidence of contrast extravasation.

The patient became chair-bound after the head injury. It was decided not to remove or reposition the Tenckhoff catheter or perform omentectomy. The rectal side of the catheter was cut short.

The pathogenesis of late perforation of the bowel has been proposed to involve intimate contact between the peritoneal catheter and the intestinal wall. The continuous pressure causes local ischaemia, eventually leading to erosion, laceration, and frank perforation.1 Lack of fluid in the peritoneal space after cessation of CAPD predisposes to pressure-induced necrosis because of loss of the fluid cushion.2 3 In our patient, perforation was unlikely when the catheter was in daily use because it did not come into continuous close contact with the bowel for any long period of time.4

In most previous studies, delayed perforation of the bowel was associated with acute peritonitis.1 3 5 6 Kagan and Bar-Khayim1 reviewed the publications from 1980 to 1995 and identified 24 cases of bowel perforation during the study period. All cases were associated with acute peritonitis, with 29% mortality and significant morbidity. The age of patients ranged from 22 to 80 years, with no gender predominance. The time to bowel perforation also ranged broadly from 0.5 to 96 months after initiation of dialysis. Sigmoid was the most common site of perforation, accounting for 14 of the 24 cases. Asymptomatic delayed perforation of the bowel by Tenckhoff catheter was rarely reported.7 8

Our patient had acute peritonitis in late 2013. The KUB showed normal position of Tenckhoff catheter (Fig 1a) . Since the Tenckhoff catheter was not functioning, omental wrap was suspected.

Later X-rays revealed progressive inferior migration of the catheter and loss of coiling of the catheter tip, suggesting perforation of the bowel (Figs 1b and 1c). The CT abdomen and pelvis confirmed perforation of the sigmoid by the Tenckhoff catheter in addition to soft-tissue fibrosis around the catheter tip (Figs 1d and 2).

In our case, in addition to the lack of peritoneal dialysis fluid, there were probably peritoneal adhesions arising from previous peritonitis that resulted in decreased bowel mobility. This in turn created a predisposition to impingement of bowel loops by the Tenckhoff catheter that subsequently led to pressure erosion and perforation.

The patient had no clinical or radiological evidence of peritonitis, possibly due to plugging of the bowel perforation site by the catheter and later sealed off by inflammatory adhesion and fibrosis. Thus, there was no leakage of faecal material from the sigmoid into the peritoneal cavity to incite inflammation and consequent faecal peritonitis. Occasionally the omentum can also surround and wall off focal inflammation to prevent extension of the inflammation to involve the rest of the peritoneal cavity, as may be seen in the formation of phlegmon or an abscess in ruptured acute peritonitis.

We present a rare but clinically important case of delayed perforation of the bowel by Tenckhoff catheter. According to this case report and several reported cases, regular flushing of the dialysis catheter and early removal if not in use (dysfunctional or not required) may help prevent this complication.

No conflicts of interest were declared by the authors.

1. Kagan A, Bar-Khayim Y. Delayed decubitus perforation of the bowel is a sword of damocles in patients on peritoneal dialysis [Letter]. Nephron 1996;74:232-3. Crossref

2. Brady HR, Abraham G, Oreopoulos DG, et al. Bowel erosion due to a dormant peritoneal catheter in immunosuppressed renal transplant recipients. Perit Dial Int 1988;8:163-5.

3. Rambausek M, Zeier M, Weinreich T, Ritz E, Rau J, Pomer S. Bowel perforation with unused Tenckhoff catheters. Perit Dial Int 1989;9:82.

4. Parvin SD, Beaman M. Ileal erosion by the Tenckhoff catheter. Perit Dial Bull 1985;5:82.

5. Valles M, Cantarell C, Vila J, et al. Delayed perforation of the colon by a Tenckhoff catheter. Perit Dial Bull 1982;2:190.

6. Thibodeaux LC. Bowel perforation associated with continuous ambulatory peritoneal dialysis. Nephron 1995;70:265. Crossref

7. Saweirs WW, Casey J. Asymptomatic bowel perforation by a Tenckhoff catheter. Perit Dial Int 2005;25:195-6.

8. Balaji V, Digard N, Wise MH. Delayed bowel erosion due to functioning chronic ambulatory peritoneal dialysis catheter. Nephrol Dial Transplant 1996;11:368-9. Crossref

A 71-year-old woman presented to us in August 2012 with a rash over both lower limbs. Blood tests revealed leukocytosis with white cell count of 22 x 10⁹ /L (neutrophil 1.6 x 10⁹ /L, lymphocytes 20 x 10⁹ /L). Serum creatinine level was 53 µmol/L and serum albumin 42 g/L. Urinalysis showed no albuminuria or microscopic haematuria. Bone marrow biopsy confirmed the diagnosis of chronic lymphocytic leukaemia (CLL). Fluorescence in-situ hybridisation showed deletion of chromosome 11q22~23. Computed tomography revealed multiple enlarged lymph nodes in different regions such as submental, bilateral jugular, left supraclavicular fossa, mediastinal, hila, axillary, porta hepatis, para-aortic and bilateral common iliac regions. Chlorambucil 2 mg twice weekly was prescribed and the patient was followed up regularly in our clinic. During this period she had two episodes of sepsis that were treated successfully with antibiotics.

In October 2013, she was noted to have progressive bilateral lower limb swelling and facial puffiness. She also reported frothy urine but no gross haematuria. She denied taking any herbs or over-the-counter medication. Physical examination was unremarkable except for pitting oedema over both lower limbs. Urinalysis revealed the presence of 10-50 red blood cells/cm². The spot urine protein-to-creatinine ratio was 13.1 g/g. Her serum creatinine concentration was 364 µmol/L (reference range [RR], 65-100 µmol/L), albumin was 32 g/L (RR, 35-52 g/L), globulin was 40 g/L (RR, 22-36 g/L), haemogloblin was 87 g/L (RR, 134-171 g/L), and white blood cell count was 26.4 x 10⁹ /L (RR, 3.7-9.2 x 10⁹ /L) [neutrophil 3.9 x 10⁹ /L, lymphocytes 22.1 x 10⁹ /L]. The liver function was normal. Anti-nuclear antibody was positive (titre 1:80, homogeneous pattern) but anti-DNA was negative. Her anti-neutrophil cytoplasmic antibodies (ANCA) were positive with perinuclear staining pattern (pANCA) and the anti-myeloperoxidase (anti-MPO) antibody titre was >100 U/mL (reference level, <5 U/mL). The complement level was normal and hepatitis serology was negative. Urine culture showed no bacterial growth. Ultrasound-guided renal biopsy was performed. Light microscopic examination showed 21 glomeruli, three of which showed global glomerulosclerosis (Fig 1). Twelve glomeruli featured crescent formation (3 had cellular crescent, 6 had fibrocellular crescent, and 3 had fibrous crescent). Fibrinoid necrosis was also identified. Nonetheless, immunohistochemical staining showed several atypical lymphoid cell aggregates composed of small- to medium-sized lymphoid cells expressing B-cell markers CD20, CD5, CD23 and LEF-1 (Fig 2). They were negative for T-cell marker CD3, follicular centre marker CD10 and cyclin D1. The overall features supported the diagnosis of ANCA-associated crescentic glomerulonephritis and renal involvement of CLL. She was given 3 days of intravenous pulse methylprednisolone 500 mg, followed by daily oral prednisolone 30 mg and cyclophosphamide 50 mg. In addition, chlorambucil was stopped and monthly rituximab (first dose 375 mg/m², subsequent doses 500 mg/m²) was administered. After 6 months, her lymphocyte count was normal and serum creatinine level was around 142 µmol/L. Proteinuria also reduced to 1.12 g/day and her last anti-MPO level was 11 U/mL.

We present a rare case of a 71-year-old woman with ANCA-associated crescentic glomerulonephritis that occurred simultaneously with renal infiltration of CLL. Such leukaemia is one of the chronic lymphoproliferative disorders characterised by a progressive accumulation of functionally incompetent lymphocytes that are monoclonal in origin. In fact, CLL can be considered to be identical to the mature (peripheral) B cell neoplasm small lymphocytic lymphoma (SLL) but at different stages along a continuum. Patients in an early stage of CLL are usually asymptomatic. The most common presentation is the incidental finding of leukocytosis, especially lymphocytosis. Other presenting signs and symptoms include malaise, weakness, anaemic symptoms, night sweating, recurrent infection, and lymphadenopathy. The diagnosis of CLL requires demonstration of lymphocytes with monoclonal B cells in either serum or bone marrow. Monoclonal B cells can be demonstrated by the expression of CD5 antigen.

The disease CLL/SLL is commonly associated with various glomerular disease entities such as minimal-change glomerulopathy, membranoproliferative glomerulonephritis, membranous glomerulopathy, focal segmental glomerulosclerosis, light-chain deposition disease, amyloidosis, and immunotactoid glomerulopathy.1 In addition, CLL can infiltrate various internal organs such as the kidneys. Previous studies have shown on autopsy that the kidneys were involved in 60% to 90% of CLL cases.2 3 Renal infiltration of CLL can be easily missed however, because it is usually asymptomatic and is not a common cause of acute kidney injury or end-stage renal disease.4 5 As a result, the interstitial inflammatory cell infiltrate in the renal biopsy specimen should be examined with immunofluorescence and electron microscopy.

Moreover, CLL can also be associated with autoimmune diseases, notably haematological diseases such as haemolytic anaemia, thrombocytopenia, and pure red cell aplasia.6 Approximately 2% of patients with CLL have associated pANCA positivity.7 Titre of ANCA has been shown to be involved in the pathogenesis of pauci-immune crescentic glomerulonephritis.8 Hence, it is not surprising that CLL can be associated with rapidly progressive glomerulonephritis (RPGN). The association between CLL/SLL and RPGN, however, has been shown in only a few case reports, and while renal histology was lacking in some of these patients, most of them were found to have positivity for pANCA and anti-MPO when serologic tests were available.1 9 10 11 12 13 14

There have been no large-scale randomised controlled trials for the treatment of CLL-related pauci-immune glomerulonephritis because of the limited number of patients. Most reported cases have been treated in the same way as other pauci-immune glomerulonephritis.9 Medication used in the treatment of RPGN such as steroid, cyclophosphamide, chlorambucil, and rituximab can also be used to treat CLL. In comparison, the combination chemotherapy for high-risk CLL—which includes fludarabine, cyclophosphamide, and rituximab—shows a higher complete response rate.15 It has been postulated that successful treatment of CLL will eventually result in resolution of RPGN.

In conclusion, we report a rare case of anti-MPO antibody–related crescentic glomerulonephritis in a patient with a known history of CLL. Awareness of this rare complication in patients with CLL with early screening, close follow-up of renal function, and timely appropriate treatment are important. Further trials may be required to determine definitive treatment when these diseases co-exist.

1. Moulin B, Ronco PM, Mougenot B, Francois A, Fillastre JP, Mignon F. Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas. Kidney Int 1992;42:127-35. Crossref

2. Barcos M, Lane W, Gomez G, et al. An autopsy study of 1206 acute and chronic leukemias (1958 to 1982). Cancer 1987;60:827-37. Crossref

3. Schwartz J, Shamsuddin A. The effects of leukemic infiltrates in various organs in chronic lymphocytic leukemia. Hum Pathol 1981;12:432-40. Crossref

4. Boudville N, Latham B, Cordingly F, Warr K. Renal failure in a patient with leukaemic infiltration of the kidney and polyomavirus infection. Nephrol Dial Transplant 2001;16:1059-61. Crossref

5. Hewamana S, Pepper C, Jenkins C, Rowntree C. Acute renal failure as the presenting feature of leukaemic infiltration in chronic lymphocytic leukaemia. Clin Exp Nephrol 2009;13:179-81. Crossref

6. Diehl LF, Ketchum LH. Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia. Semin Oncol 1998;25:80-97.

7. Cil T, Altintas A, Isikdogan A, Batun S. Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin’s and non-Hodgkin lymphoma: a single center experience. Int J Hematol 2009;9:52-7. Crossref

8. Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 2002;110:955-63. Crossref

9. Henriksen KJ, Hong RB, Sobrero MI, Chang A. Rare association of chronic lymphocytic leukemia/small lymphocytic lymphoma, ANCAs, and pauci-immune crescentic glomerulonephritis. Am J Kidney Dis 2011;57:170-4. Crossref

10. Biava CG, Gonwa TA, Naughton JL, Hopper J Jr. Crescentic glomerulonephritis associated with nonrenal malignancies. Am J Nephrol 1984;4:208-14. Crossref

11. Rivera M, González C, Gonzalo A, Quereda C, Fogué L, Ortuño J. Vasculitis associated with non-Hodgkin’s lymphoma. Nephron 1993;65:167-8. Crossref

12. Dussol B, Brunet P, Vacher-Coponat H, Bouabdallah R, Chetaille P, Berland Y. Crescentic glomerulonephritis with antineutrophil cytoplasmic antibodies associated with chronic lymphocytic leukaemia. Nephrol Dial Transplant 1997;12:785-6. Crossref

13. Tisler A, Pierratos A, Lipton JH. Crescentic glomerulonephritis associated with p-ANCA positivity in fludarabine-treated chronic lymphocytic leukaemia. Nephrol Dial Transplant 1996;11:2306-8. Crossref

14. Hamidou MA, El Kouri D, Audrain M, Grolleau JY. Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia. Ann Rheum Dis 2001;60:293-5. Crossref

15. Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28:1756-65. Crossref

Click here to watch a video clip showing robot-assisted laparoscopic hemi-hepatectomy with biliary reconstruction

An 83-year-old male was referred to us for deranged liver function in December 2010. There was mildly elevated bilirubin level of 36 µmol/L, alkaline phosphatase level of 281 µmol/L, and transaminase level of 98 µmol/L. Tumour markers (carcinoembryonic antigen, alpha-fetoprotein, and carbohydrate antigen 19-9) were normal. Ultrasonography revealed a markedly dilated common bile duct (CBD) and intrahepatic ducts with irregular mural lesions.

Endoscopic retrograde cholangiopancreatography (ERCP) showed a grossly dilated CBD and intrahepatic ducts filled with thick mucus and multiple large filling defects. Brush cytology revealed atypical cells. A nasobiliary drainage catheter was inserted for biliary decompression. Bilateral percutaneous transhepatic biliary drainage (PTBD) catheters were later inserted due to inefficient nasobiliary drainage.

Further evaluation by computed tomographic scan showed dilatation of the whole biliary system with multiple papilloma-like lesions as shown in Figure 1. The presence of mucus in the biliary tree and image findings raised the suspicion of biliary papillomatosis. In order to localise and assess the extent of involvement, intra-operative choledochoscopy was performed via the PTBD tract. The PTBD tract was serially dilated up to 14 Fr to allow passage of a choledochoscope. Multiple biliary papillomas over the left hepatic duct, hilar bifurcation, and upper main bile duct were visualised. The right biliary system, lower CBD, and ampullary region were disease-free. After thorough assessment by intra-operative choledochoscopy, left hepatectomy and main bile duct excision with right hepatico-jejunostomy via robot-assisted laparoscopic approach was performed.

The patient was placed in the reverse Trendelenburg position with legs spread apart, and a 5- to 12-mm subumbilical port was inserted with the establishment of carbon dioxide pneumoperitoneum. After diagnostic laparoscopy, five trocars were inserted under direct vision. The extent of disease was assessed by intra-operative ultrasonography (BK Medical, Denmark). The da Vinci S Surgical System (Intuitive Surgical Inc, Sunnyvale [CA], US) was brought into position over the patient’s head and docked in. The assistant surgeon stayed on the right side of the patient and performed suction, stapling, and clipping through an assistant port over the right lower quadrant.

The intended extent of parenchymal resection was first marked on the liver surface with electrocautery. The main extrahepatic bile duct was dissected and slung with vascular tape. The right hepatic duct and lower CBD were transected and confirmed to have clear resection margins on frozen section. Porta dissection was performed. The left hepatic artery and left porta vein were dissected and transected. The main and right hepatic artery, and main and right portal vein were identified and protected. Left hemihepatectomy was performed with an ultrasonic surgical aspirator (SonoSurg, SS; Olympus Medical Systems Corporation, Tokyo, Japan) and coagulative scissors, under hemivascular inflow control. Large branches of vascular structures were controlled with endostaplers. A right hepatico-jejunostomy via Roux-en-Y reconstruction was fashioned with 3-0 poliglecaprone 25 (Monocryl, Ethicon; Johnson & Johnson, Amersfoort, The Netherlands) sutures intracorporeally. The side-to-side jejunojejunostomy was performed and the enterotomy site closed intracorporeally with an endostapler and 3-0 monocryl sutures. The specimen (Fig 2) was delivered via the extension of the left abdominal port. Operating time was 367 minutes and operative blood loss was 200 mL. The postoperative course was uneventful and the patient was discharged on postoperative day 13. Histopathological examination revealed extensive papillomatosis with villous adenomatous changes over both left hepatic ducts and the CBD associated with moderate-to-severe dysplasia. There was no evidence of invasion to suggest malignant transformation. At 50-month follow-up, the patient remained disease-free with no further biliary obstruction.

Discussion

Biliary papillomatosis is a rare condition characterised by papillary proliferation of the lining columnar epithelium of the bile ducts. It was first reported by Chappet1 in 1894 and was initially thought to be an entity with low malignant potential. Malignant transformation, however, is noted in 20% to 50% of cases as a consequence of adenoma carcinoma sequence.2 3

Middle-aged to elderly patients are commonly affected with a slight male predominance. The clinical presentation varies from being asymptomatic, as in our patient, to the presence of recurrent abdominal pain, obstructive jaundice, or recurrent cholangitis due to biliary obstruction by mucus.

The exact pathogenesis remains to be elucidated, but biliary papillomatosis is associated with conditions such as recurrent pyogenic cholangitis and congenital choledochal cyst. It has been postulated that longstanding irritation by stones or infection stimulates reactive hyperplasia with subsequent dysplasia in the biliary system.

Despite considerable improvements in imaging techniques, diagnosis remains a challenge as the presenting symptoms are more commonly caused by choledocholithiasis. Ultrasonography and computed tomography reveal intrabiliary masses with cystic dilatation in the proximal biliary tree. On the other hand, ERCP or magnetic resonance cholangiopancreatography shows an irregular filling defect that causes obstruction with proximal dilatation. The presence of mucobilia should raise the suspicion of biliary papillomatosis.

Histopathological examination reveals that the biliary system is often replaced by velvety papillary growth that possesses a fibrovascular core lined by columnar epithelium with varying degrees of cellular atypia.

Management is difficult due to the diffuse nature of the disease. A range of treatment strategies that include local ablation, photodynamic therapy, radical excision, or total hepatectomy with liver transplantation have been reported. Local ablative therapy and curettage, and radical excision with clear resection margins are associated with better survival.2 4

Accurate localisation and assessment of the extent of disease involvement remains pertinent to an accurate choice of treatment. In a Korean series by Lee et al,2 curative resection was associated with significantly better survival (60 months in curative resection vs 36 months in palliative surgery group); similar results were demonstrated by another series of 18 cases in China.5 Due to the high propensity for diffuse involvement, recurrence and malignant transformation, timely diagnosis and radical resection remain the cornerstone for successful treatment.

The advent of robotic surgery has brought about revolutionary changes in current surgical developments, but the feasibility and benefits in hepatobiliary surgeries are yet to be explored. Deep anatomical locations, complex vascularity, and large organ volume in hepatobiliary surgery often pose a challenge to the conventional laparoscopic approach. Such hurdles can be overcome by robotic surgery: recent studies have shown that a robot-assisted approach offers a safe and feasible option for hepatobiliary surgery with promising results.6 7 8 9 10 The enhanced dexterity of EndoWrist (Intuitive Surgical Inc, Sunnyvale [CA], US), with its 7 degrees of freedom of movement, allows meticulous dissection and precise tissue handling, enabling intracorporeal suturing even in the most technically demanding areas that would otherwise be impossible to access in conventional laparoscopic surgery. The three-dimensional stereoscopic video system with magnification enhances visualisation and depth perception. The third robotic arm also allows better organ retraction. The improving technical abilities of the robotic system for dissection and suturing extend the indications of minimally invasive liver surgery to liver resection requiring a biliary reconstruction. Without any doubt, the operation described in this case requires high technical skill and experience, and cannot be quickly introduced into routine practice. We performed this operation following accumulation of 10 years’ experience of conventional laparoscopic liver surgery and 2 years’ experience of robotic liver resection and robotic biliary surgery.8 9 10 11 12 Nonetheless, we believe that with the increasing popularity of robotic surgery, the required skill can be acquired with time. With the help of a robotic system, unilateral hepatico-jejunostomy reconstruction and porta structure dissection can be performed more easily than with the conventional laparoscopic technique.

In conclusion, the robotic approach to treatment of biliary papillomatosis is feasible and safe in selected patients. It also has the advantage of being minimally invasive.

1. Chappet V. Cancer epithelial primitif du canal cholédoque. Lyon Med 1894;76:145-57.

2. Lee SS, Kim MH, Lee SK, et al. Clinicopathologic review of 58 patients with biliary papillomatosis. Cancer 2004;100:783-93. Crossref

3. Wu SD, Lu CD, Lu CJ, Huang J, Zhou J. Mucin-producing intrahepatic biliary papillomatosis. Surg Today 2010;40:845-50. Crossref

4. Ludwig L, Büchler P, Kleeff J, et al. Multidisciplinary treatment of aggressive and rapidly progressing biliary papillomatosis. Dig Dis Sci 2010;55:3627-9. Crossref

5. Jiang L, Yan LN, Jiang LS, et al. Biliary papillomatosis: analysis of 18 cases. Chin Med J (Engl) 2008;121:2610-2.

6. Giulianotti PC, Sbrana F, Coratti A, et al. Totally robotic right hepatectomy: surgical technique and outcomes. Arch Surg 2011;146:844-50. Crossref

7. Choi GH, Choi SH, Kim SH, et al. Robotic liver resection: technique and results of 30 consecutive procedures. Surg Endosc 2012;26:2247-58. Crossref

8. Lai EC, Tang CN, Yang GP, Li MK. Multimodality laparoscopic liver resection for hepatic malignancy—from conventional total laparoscopic approach to robot-assisted laparoscopic approach. Int J Surg 2011;9:324-8. Crossref

9. Lai EC, Tang CN, Li MK. Robot-assisted laparoscopic hemi-hepatectomy: technique and surgical outcomes. Int J Surg 2012;10:11-5. Crossref

10. Lai EC, Yang GP, Tang CN. Robot-assisted laparoscopic liver resection for hepatocellular carcinoma: short-term outcome. Am J Surg 2013;205:697-702. Crossref

11. Lai EC, Tang CN, Ha JP, Li MK. Laparoscopic liver resection for hepatocellular carcinoma: ten-year experience in a single center. Arch Surg 2009;144:143-7; discussion 148. Crossref

12. Lai EC, Tang CN, Yang GP, Li MK. Minimally invasive surgical treatment of hepatocellular carcinoma: long-term outcome. World J Surg 2009;33:2150-4. Crossref

Churg-Strauss syndrome (CSS) is a small and medium-sized vessel vasculitis that can affect different organs. The usual presentation is sub-optimised control of asthma together with involvement of other organs such as the heart, skin, and nervous system. It seldom presents with isolated neurological symptoms and has thus far not been reported from an orthopaedic aspect. We report a case of CSS in a patient who presented with neurological symptoms and who was admitted to the orthopaedic ward via casualty because of lower limb weakness and numbness.

A 66-year-old Chinese woman was admitted to the orthopaedic ward for 2 weeks in May 2013 because of weakness and numbness in both lower limbs. She had a more than 10 years’ history of asthma that was controlled with an inhaled bronchodilator and oral theophylline and terbutaline. The patient was prescribed an oral steroid intermittently for acute control. From January 2012 until the current admission, she had also been taking a leukotriene receptor antagonist (montelukast).

On admission, the patient complained of severe dysesthesia over both lower limbs, mainly below knee level. There was mild left proximal thigh pain. She had no low back pain and denied a history of recent trauma. The symptoms rendered the patient unable to walk.

Upon physical examination, she was afebrile, and cardiopulmonary and dermatological examination was unremarkable. Neurological examination revealed decreased sensation over both lower limbs in a glove and stocking distribution. Power of the muscles supplied by the peroneal and tibial nerves was grade 4 according to Medical Research Council grading system. Reflexes were diminished over both lower limbs. Per rectal examination revealed normal anal tone.

Blood tests revealed elevated white cell count to 28.07 x 10⁹ /L with a predominance of eosinophils (20.46 x 10⁹ /L). C-reactive protein was 65 mg/L. Erythrocyte sedimentation rate was 52 mm/h. Serum calcium, phosphate, alkaline phosphatase and creatine kinase level were normal. Sepsis workup including blood culture and urine culture were negative (Table).

Radiography of the lumbar spine revealed grade-one spondylolisthesis at the lumbar 4 and 5 level. Radiography of the pelvis was unremarkable. Chest radiography showed slightly hyperinflated lung. Subsequent magnetic resonance imaging with contrast of the lumbar spine and pelvis was performed in view of the radiographic findings of the lumbar spine and the neurological deficit in the lower limbs. There was neither evidence of nerve root and cord compression nor infection around the lumbar spine.

Nerve conduction study showed absence of the compound muscle action potential (CMAP) of the right peroneal nerve recorded at the extensor digitorum brevis muscle. The CMAP was also decreased over bilateral tibialis anterior muscles. These results were suggestive of an axonal type of motor neuropathy over bilateral peroneal nerves and a sensory type of axonal neuropathy over the right lower limb. There was no involvement of the upper limbs.

Left sural nerve biopsy revealed epineurial extravascular eosinophils and vasculitis associated with axonal degeneration (Fig). There was one small epineurial artery infiltrated by eosinophils, polymorphs, and lymphocytes. Vague granuloma were present in the vascular wall. These features were consistent with CSS based on the American College of Rheumatology Classification criteria.1 The Table summarises the investigations.

A rheumatologist was consulted who diagnosed CSS with peripheral neuropathy. Montelukast was discontinued in view of the possible association of the CSS. Oral prednisolone 40 mg daily was prescribed to the patient and an oral bisphosphonate was given to prevent osteoporosis. Distal lower limb power improved to grade 5 shortly following steroid treatment and there was marked improvement in pain and numbness. The eosinophil count and elevated inflammatory markers reduced rapidly over 6 days. The patient was discharged from the orthopaedic ward 2 weeks after treatment and was able to walk with a stick. The patient has been referred to a day hospital for further rehabilitation.

Churg-Strauss syndrome is an entity frequently described by rheumatologists in the literature.2 It has seldom been reported by an orthopaedic surgeon. This case illustrates that common symptoms such as pain and numbness, frequently encountered when treating orthopaedic patients, may not be necessarily due to an orthopaedic problem. It may be a medical disease that requires prompt and specific treatment.

Allergic granulomatosis angiitis, or CSS, is a type of antineutrophil cytoplasmic antibody–associated small-vessel systemic vasculitis. Other diseases under the same group include microscopic polyangiitis and granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis.3 It was first described in 1951 by Dr Jacob Churg and Dr Lotte Strauss at Mount Sinai Hospital and is characterised by eosinophilic vasculitis that affects the small and medium-sized vessels. It describes the clinical symptoms of the pathological entity allergic angiitis and granulomatosis. The American College of Rheumatology has recommended that diagnosis of the syndrome is considered when four of the following features are present: (1) asthma, (2) eosinophils constituting more than 10% of the white cell count, (3) neuropathy, (4) non-fixed pulmonary infiltrates on radiography, (5) extravascular granulomas, and (6) abnormalities of the paranasal sinuses.1 The presence of four or more criteria yields a diagnostic sensitivity of 85% and a specificity of 99%.1

Despite variable clinical manifestations, pathological findings will include necrotising eosinophilic vasculitis that may result from endothelial cell adhesion and leukocyte activation, with subsequent necrotising vasculitis in several organ systems.

The pathogenesis of the syndrome is unclear, but it has been shown that HLA-DRB3 is a genetic risk factor for development. There have been reports about the strong association between CSS and the use of a leukotriene receptor antagonist (LTRA) such as montelukast. The mechanism by which LTRAs might cause eosinophilic vasculitis remains unclear, however. It is known that LTRAs do not inhibit leukotriene B4 (LTB4), which is a powerful chemoattractant for eosinophils. This could lead to increased plasma levels of LTB4 and trigger eosinophilic inflammation. Nevertheless, LTRA has a somewhat causative role in the development of CSS. A controlled study with a large number of patients is required to verify this conclusion.

The clinical presentation is variable. Some people have only mild symptoms, while others experience severe or life-threatening complications. There are three stages of CSS, but not every patient will develop all three phases or in the same order. They include:
(1) Allergic stage: the first stage of the syndrome in which the patient develops a number of allergic reactions including asthma, hay fever, and sinusitis.
(2) Eosinophilic stage: hypereosinophilia is found in the blood or tissue causing serious local damage. The lungs and digestive tract are most often involved. The symptoms may be relapsing and remitting and last for months or years.
(3) Vasculitic stage: the hallmark of this stage is blood vessel inflammation. The blood vessels are narrowed by inflammation and blood flow to tissue is jeopardised. During this phase, a feeling of general ill-health along with unintended weight loss, lymphadenopathy, weakness, and fatigue may occur.

Asthma is the central feature of CSS and precedes the systemic manifestations in almost all cases. Upper airway findings can include sinusitis, allergic rhinitis, and nasal polyps. Cardiac involvement represents the major cause of mortality. Granulomatous infiltration of the myocardium and coronary vessel vasculitis are the most common lesions. Congestive heart failure may develop rapidly and is often responsible for the mortality. Gastro-intestinal involvement such as abdominal pain, diarrhoea, and bleeding may also occur. Bowel perforation is the most severe manifestation and is one of the major causes of death. The glomerular lesion that typifies CSS is focal segmental glomerulonephritis with necrotising crescents. Its involvement is one of the poor prognostic factors. Arthralgias are frequent but arthritis with local inflammatory findings is rare, and joint deformity and radiographic erosions are usually not seen. Large articular joints are affected more than small joints. The symptoms usually regress quickly with treatment. Skin involvement occurs in 50% to 68% of patients and reflects the predilection for small vessels. Lesions are red or violaceous, and occur primarily on the scalp and the limbs or hands and feet. They are often bilateral and symmetrical.4

Peripheral neuropathy, as in our case, is common in patients with CSS (65-75%).5 6 The initial symptoms of neuropathy usually include an acute onset of tingling or painful paresthesia in the extremities. These symptoms predominantly occur in the distal portions of the extremities, particularly the lower limbs. In the initial phase, the distribution of sensory impairment usually takes the form of a mononeuritis multiplex pattern. As the disease progresses, it eventually evolves into a polyneuropathic pattern. Muscle weakness, to a variable extent and degree of asymmetry, may also be evident. There will be decreased or absent deep tendon reflexes corresponding to the distribution of nerves involved. Electromyography reveals axonal nerve involvement and often detects more extensive involvement than the clinical symptoms would indicate. With treatment, mononeuritis multiplex regresses progressively and patients may recover without sequelae. Prompt diagnosis and treatment are of paramount importance in managing CSS with neuropathy. If medical treatment is delayed, atrophy and weakness of the limbs may be irreversible and will require additional rehabilitation therapy including strengthening exercises, balance training, and ambulation training.

In the treatment of CSS, as with other forms of vasculitis, the symptoms respond to corticosteroids or other immunosuppressive drugs, eg cyclophosphamide and methotrexate.7 If refractory to these agents, intravenous immunoglobulin is the treatment of choice. Leukocytosis, eosinophilia, and raised erythrocyte sedimentation rates usually respond promptly after administration of these agents. Neuropathic pain also decreases rapidly in 85% of patients. There is speculation that the initial clinical course and the degree of systemic inflammatory involvement may influence long-term functional prognosis. Recent trials of treatment include immunomodulators such as rituximab, an anti-CD20 monoclonal antibody, and tumour necrosis factor–alpha.8

In this article, we have reviewed the clinical features, diagnostic criteria, and treatment options of CSS. In middle-aged or elderly patients, lower limb numbness and pain are frequently attributed to the degenerative spine with stenosis or nerve root compression. It is tempting to conclude that a patient has spinal stenosis or lumbar spondylosis in the presence of degenerative lumbar spine radiographs. This case highlights the need for clinicians to be vigilant for these manifestations in addition to the various diagnoses of spinal pathology when a patient presents with limb numbness and weakness together with a history of asthma and raised eosinophil count. Because signs and symptoms are both numerous and at times unassuming, it is notoriously difficult to diagnose CSS at the very initial phase. Nonetheless, significant neuropathic involvement may be prevented if a patient receives adequate therapy to induce remission of disease and prevent relapse. With treatment, most of the symptoms in any of the three phases can be relieved. We would like to raise the awareness of such an entity in treating patients with neuropathy. Close collaboration with rheumatologists in treating such a complex illness, including prompt diagnosis by performing nerve biopsy by an orthopaedic surgeon and prompt medical treatment by a rheumatologist, is the key to successful management.

1. Masi AT, Hunder GG, Lie TT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-100. Crossref

2. Churg J, Strauss L. Allergic granulomatosis, allergic rhinitis, and periarthritis nodosa. Am J Pathol 1951;27:277-301.

3. Falk RJ, Gross WL, Guillvein L, et al. Granulomatosis with polyangiitis (Wegener’s): An alternative name for Wegener’s granulomatosis. Arthritis Rheum 2011;63:863-4. Crossref

4. Guillevin L, Pagnoux C, Mouthon L. Churg-Strauss syndrome. Semin Respir Crit Care Med 2004;25:535-45. Crossref

5. Sehgal M, Swanson JW, DeRemee RA, Colby TV. Neurologic manifestations of Churg-Strauss syndrome. Mayo Clin Proc 1995;70:337-41. Crossref

6. Hattori N, Ichimura M, Nagamatsu M, et al. Clinicopathological features of Churg-Strauss syndrome–associated neuropathy. Brain 1999;122:427-39. Crossref

7. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA 2007;298:655-69. Crossref

8. Thiel J, Hässler F, Salzer U, Voll RE, Venhoff N. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Arthritis Res Ther 2013;15:R133. Crossref