Endoscopic retrograde cholangiopancreatography (ERCP) is a standard endoscopic technique for treating biliary obstruction and cholangitis. The presence of surgically altered gastrointestinal anatomy, however, poses a major technical difficulty to the procedure due to the long and tortuous access to the small bowel. We report a three-case series with successful attempts at short double-balloon enteroscopy (DBE)–assisted ERCP in patients with postoperative gastrointestinal anatomy. The enteroscope employed was EC-450BI5, Fujifilm endoscopy (Fig 1) and the sedation agents used in all procedures were dexmedetomidine and fentanyl continuous infusion combined with bolus midazolam.

A 76-year-old man was admitted to our hospital in December 2015 with acute cholangitis that presented as fever and deranged liver function tests (LFT) with predominant elevation of alkaline phosphatase (ALP). He had a history of stroke, hyperlipidaemia, and a Billroth II gastrectomy performed 30 years ago. Blood cultures grew Escherichia coli. Ultrasonography of the hepatobiliary system revealed a 5-mm stone in the common bile duct (CBD).

The first ERCP using a standard side-view duodenoscope and end-view gastroscope failed to identify the papilla. He continued to receive antibiotic treatment, with the fever reduced but liver biochemistry remained elevated. The DBE-assisted ERCP was performed 2 weeks later with an enteroscope of 152-cm working length. The papilla was reached over the afferent limb of the small bowel by manipulation of the overtube only (no balloon inflation), followed by successful cannulation of the CBD. Cholangiogram revealed a 1.2-cm dilated CBD with two intraductal filling defects (Fig 2a). Pre-cut papillotomy on-stent was performed with pre-insertion of a 7-French 7-cm plastic biliary stent. The plastic stent was removed after papillotomy and the papilla was dilated using a controlled radial expansion (CRE) balloon dilator of 12-mm size and subsequently stones were removed by a basket. The ERCP procedure was completed in 115 minutes and there were no complications. The patient’s LFT had normalised at a follow-up 3 weeks later.

An 80-year-old man presented in January 2016 with a history of hypertension, pulmonary fibrosis, and cerebral infarct. A Billroth II gastrectomy had been performed 10 years previously for gastrointestinal bleeding. He had an episode of acute cholangitis 4 months ago. Endoscopic retrograde cholangiopancreatography using a standard end-view gastroscope failed to reach the papilla and the infection resolved after a course of antibiotic. Follow-up magnetic resonance cholangiopancreatography 3 weeks earlier had revealed a 1.2-cm distal CBD stone with the CBD dilated to 1.7 cm. He then attended the hospital again for fever, E coli septicaemia, and an obstructive pattern of liver derangement; bilirubin level was 93 µmol/L and ALP level was 1224 U/L. Percutaneous transhepatic biliary drainage was established and antibiotics were continued until DBE-assisted ERCP was performed 2 weeks later. With the push-pull manoeuvre, the blind end of the afferent loop was reached. Initially, a nearby minor papilla was mistaken as the major papilla and repeated attempts failed to cannulate it.

The true major papilla was then identified 5 cm proximal to the minor papilla and pre-cut papillotomy was performed due to difficult cannulation. The impacted CBD stone was removed following papillotomy and balloon sphincteroplasty was performed with a 12-mm CRE balloon. Subsequent cholangiogram was clear with a 1.5-cm dilated CBD. The operating time was 163 minutes. The patient remained asymptomatic and LFT had normalised at a follow-up 1 month later.

A female patient aged 81 years with a history of mild Parkinson’s disease had undergone gastrectomy 30 years ago for peptic ulcer disease. She presented to our hospital in February 2016 for biliary pancreatitis with sudden onset of jaundice associated with epigastric pain. Amylase level was elevated to 698 U/L, bilirubin level to 35 µmol/L, and an ALP level of 1001 U/L. Ultrasonography of the hepatobiliary system detected grossly dilated intrahepatic ducts (IHD) and the CBD measured up to 2.4 cm in diameter with one obstructing CBD stone measuring 1.5 cm. The first gastroscopy confirmed a previous total gastrectomy with Roux-en-Y reconstruction. Percutaneous transhepatic biliary drainage was attempted but failed due to the resolution of the IHD dilatation. The patient was then managed conservatively with antibiotics and a DBE-assisted enteroscopy was scheduled 3 weeks later. The 152-cm DBE identified the blind end of the afferent limb while the endoscope advanced to 140 cm from the incisors after push-pull manoeuvre (Fig 2b to d). Successful guidewire cannulation was followed with a cholangiogram that showed a dilated CBD with no filling defect. In view of the recent history of biliary obstruction and the possibility of a passed stone, the papilla was dilated to 13.5 mm with the CRE balloon and good bile drainage was observed. The operating time was 130 minutes. The major difficulty encountered was that the tip of the enteroscope was very unstable making it difficult to maintain the distal blind end and it was easily slipped out proximally. As such, repeated endoscope manipulation was required to achieve optimal positioning. Postoperatively, the patient was well, bilirubin normalised, and ALP level had reduced to 266 U/L at 1-month follow-up.

Balloon enteroscopy–assisted ERCP using either single-balloon enteroscopy or DBE has been reported to be an effective modality for ERCP in these patients.1 2 3 Traditional DBE with 200-cm length and narrow (2.2-mm) accessory working channel limits the utilisation of conventional ERCP accessories. Recent attempts with a short 152-cm DBE have been highly successful.1 2 4 To date, there have been approximately 200 reports of patients who have undergone ERCP using this short DBE procedure. The success rate for reaching the blind end of the afferent limb was 86% to 100%; it is not inferior to that achieved using a long-type balloon enteroscope.4 The short-type enteroscope accommodates the use of most available accessories to perform ERCP-related procedures such as sphincterotomy, balloon dilatation, stone extraction, and deployment of plastic or metallic stents.

In our small series, all patients ran an uneventful course during the perioperative and postoperative period and none had any apparent complications. The overall procedural complication rate has been reported to be 8% to 10%, with the rate of major complications of perforation or emphysema being around 3.5%.4 The risk of complications, however, may vary according to different surgical approaches with consequent significant differences in the endoscopic techniques anticipated.3 4 5 Since it is a relatively new and evolving endoscopic technique, these rates are still experience-dependent and patients should be closely observed after the procedure.

The ERCP in the patient with Roux-en-Y reconstruction posed particular technical difficulties. The endoscopist should review previous surgical reports in detail to map and anticipate the endoscopic view at the anastomotic site. On reaching the Roux-en-Y anastomosis, identification of the pancreatobiliary limb is often difficult. After choosing either limb, the endoscopist could perform endoscopic marking by a clip or Indian ink tattoo at the entrance of the chosen limb (Fig 2c). If the chosen limb is confirmed wrong under fluoroscopy, the endoscopist can return the endoscope to the Roux-en-Y anastomosis and then insert the endoscope into the other limb. A marking at the entrance of a limb has been shown to be useful as it avoids repeated misidentification of the limb to be entered.6

Barotrauma is the major cause of intestinal perforations and may be a result of excessive air insufflation forming a closed loop between the blind end and the inflated overtube or enteroscope balloon.7 Use of carbon dioxide insufflation instead of air insufflation may reduce the chance of this closed-loop phenomenon. Additionally, use of a transparent hood at the tip of the enteroscope with instillation of water into the intestinal lumen has also been suggested to maintain the endoscopic view without gas insufflation and avoid consequent barotrauma.8

With regard to the cannulation techniques, the catheter exits from a 7 o’clock direction of the enteroscope during DBE-assisted ERCP. Endoscopists should attempt to locate the papilla at 6 o’clock of the endoscopic view to facilitate biliary cannulation (Fig 2b). In case of an unstable endoscopic manoeuvre, an inflated enteroscope balloon may help to grip the intestine and stabilise the manipulation. In cases where the papilla is located at 11 to 12 o’clock in the endoscopic view, the overtube balloon should remain inflated and the enteroscope rotated to solve difficult cannulation.6

In conclusion, short DBE-assisted ERCP is a safe and effective endoscopic method to treat patients with surgically altered anatomy and biliary conditions. Nonetheless local experience in enteroscopy-assisted ERCP, particularly using the short DBE, is scant because of the unavailability of the endoscopic devices. Further discussion and training opportunities are encouraged to consolidate experience and minimise procedural complications in future practice.

1. Moreels TG. Altered anatomy: enteroscopy and ERCP procedure. Best Pract Res Clin Gastroenterol 2012;26:347-57. Crossref

2. Cheng CL, Liu NJ, Tang JH, et al. Double-balloon enteroscopy for ERCP in patients with Billroth II anatomy: results of a large series of papillary large-balloon dilation for biliary stone removal. Endosc Int Open 2015;3:E216-22. Crossref

3. Mönkemüller K, Bellutti M, Neumann H, Malfertheiner P. Therapeutic ERCP with the double-balloon enteroscope in patients with Roux-en-Y anastomosis. Gastrointest Endosc 2008;67:992-6. Crossref

4. Kato H, Tsutsumi K, Harada R, Okada H, Yamamoto K. Short double-balloon enteroscopy is feasible and effective for endoscopic retrograde cholangiopancreatography in patients with surgically altered gastrointestinal anatomy. Dig Endosc 2014;26 Suppl 2:130-5. Crossref

5. Katanuma A, Yane K, Osanai M, Maguchi H. Endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy using balloon-assisted enteroscope. Clin J Gastroenterol 2014;7:283-9. Crossref

6. Hatanaka H, Yano T, Tamada K. Tips and tricks of double-balloon endoscopic retrograde cholangiopancreatography (with video). J Hepatobiliary Pancreat Sci 2015;22:E28-34. Crossref

7. De Koning M, Moreels TG. Comparison of double-balloon and single-balloon enteroscope for therapeutic endoscopic retrograde cholangiography after Roux-en-Y small bowel surgery. BMC Gastroenterol 2016;16:98. Crossref

8. Yamamoto H. Be aware of the fatal risk of air embolism. Dig Endosc 2014;26:23. Crossref

An 85-year-old man presented with a history of odynophagia since March 2015. He was a chronic smoker but did not drink alcohol. He had a medical history of hypertension, diabetes mellitus, and gout. He was first seen by us in April 2015. At the first presentation, physical examination revealed an irregular 3-cm ulcerative mass arising from the left tonsil (Fig 1). The rest of his oral cavity was otherwise normal and there was no cervical lymphadenopathy. Carcinoma of the left tonsil was suspected. Computed tomographic (CT) scan of the head and neck disclosed a non-specific soft tissue thickening and mucosal contrast enhancement at the left side of the oropharynx. Transoral punch biopsy of the left tonsillar mass was performed. Histopathology revealed no evidence of malignancy with heavy stromal infiltration by neutrophils, lymphocytes, and plasma cells plus focal microabscess formation. No granuloma or fungal elements were seen.

Subsequent upper gastrointestinal endoscopy was performed and disclosed the left tonsillar mass with no other abnormalities within the hypopharynx, oesophagus, or stomach. Because of the progressive odynophagia, a nasogastric feeding tube was inserted; as there was no improvement and the diagnosis was still elusive, left tonsillectomy was performed on the same day and was uneventful.

Histopathological examination of the left tonsil showed lymphoid tissue with preserved architecture present beneath the stratified squamous epithelium. Hyperplastic lymphoid follicles with germinal centre surrounded by mantle cells were present. Plasma cells were seen at the interfollicular area. There were no malignant cells. Immunostaining revealed more than 90% of plasma cells per high-power field with an immunoglobulin (Ig) G4:IgG ratio of more than 40% (Fig 2). The final diagnosis was IgG4-related disease of the left tonsil.

The patient refused workup with positron emission tomography–CT scan but clinically there was no feature of systemic IgG4-related disease so steroids were not prescribed. His odynophagia gradually improved and he could tolerate oral feeding with congee. The feeding nasogastric tube was removed. Unfortunately, the patient had a depressive mood and general debility. He eventually died of pneumonia in September 2015.

Immunoglobulin G4–related disease is a fibroinflammatory condition often associated with elevated serum IgG4 level.1 It is a multi-organ entity that encompasses various conditions formerly considered to be unrelated, single-organ diseases.2 It is notorious for its resemblance to malignant disease such as carcinoma of the pancreas. It is a source of undue anxiety for both patients and clinicians as the diagnosis may be difficult if the index of clinical suspicion for IgG4-related disease is low. Systemic symptoms (asthenia, weight loss, or fever) may occur in a minority of patients. The disease can affect the pancreas (autoimmune pancreatitis with abdominal pain), biliary tree (sclerosing cholangitis with jaundice), salivary glands or lacrimal gland (parotid, submandibular and lacrimal gland enlargement), lymph nodes, kidneys (tubulointerstitial nephritis with renal failure), and retroperitoneum (ureteric stricture).2

Measuring the serum IgG4 level is useful to establish the diagnosis of this uncommon disease3 and may avoid unnecessary diagnostic surgery. Although serum IgG4 level was initially thought to be a key diagnostic feature of IgG4-related disease, more recent evidence has devalued the significance of a raised level. The key to diagnosis is immunohistochemical demonstration of tissue infiltration by IgG4-bearing plasma cells and morphological evidence of lymphoplasmacytic infiltrates, storiform fibrosis, and obliterative phlebitis.2 Serum IgG4 assay was not done as this investigation was not available at our hospital. Nonetheless the diagnosis of IgG4-related disease of tonsil in this patient was obvious based on the histopathological examination with IgG4 immunostains.

Umehara et al4 proposed a set of criteria for the diagnosis of IgG4-related disease designed to be used irrespective of the specific organ involvement. The criteria are (1) serum IgG4 concentration of >135 mg/dL and (2) >10 IgG-positive plasma cells demonstrated per high-power field, of which >40% are IgG4-positive cells. Nevertheless the sensitivity is low for the diagnosis of autoimmune pancreatitis based on these criteria.

Of note, IgG4-related disease can manifest at the head and neck region. Kuttner’s tumour of the submandibular gland has been well reported and often masquerades as carcinoma.5 Nonetheless IgG4-related disease within the oral cavity is very rare. To the best of our knowledge, only one case of simultaneous IgG4-related lesions affecting the left border of the tongue and right tonsil has been reported in the literature.6 This patient presented with an elevated and nodular mass devoid of surface ulceration, associated with a generalised skin rash. The oral and cutaneous lesions gradually resolved after therapy with steroid.6 In contrast, our patient had an ulcerative mass without any skin rash. Both cases were initially suspected to be squamous cell carcinoma because of the alarming clinical features.

Steroid remains the mainstay of treatment for IgG4-related disease. It should be started early in order to prevent tissue fibrosis and thus irreversible organ damage, except in cases of asymptomatic disease of the submandibular gland or lymph node.7 Radiological abnormalities often vanish following the commencement of steroid therapy. Unfortunately, disease relapse is not uncommon after steroid therapy is tapered. There is no evidence to support the effectiveness of adding conventional steroid-sparing agents (eg azathioprine, methotrexate, or cyclophosphamide) to sustain remission for IgG4-related disease.7 Although remission can be achieved in more than 80% of patients with induction steroid therapy, some clinicians support the use of maintenance steroid at 5 mg or 2.5 mg daily for a durable response. However, disease may flare in a quarter of patients despite maintenance therapy. Moreover, the optimal duration for maintenance treatment is uncertain and the morbidity associated with steroid, although in low dose, is not negligible. Fortunately, repeated induction therapy with steroid for disease relapse is normally effective.7

In summary, IgG4-related disease can involve the tonsils and masquerade as tonsil carcinoma. Clinicians should consider IgG4-related disease as one of the differential diagnoses for a suspicious tonsillar mass. Early diagnosis of tonsillar mass with biopsy is essential to exclude tonsil carcinoma and to allow prompt steroid treatment for IgG4-related disease of tonsil which is curable.

1. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:1181-92. Crossref

2. Stone JH, Brito-Zerón P, Bosch X, Ramos-Casals M. Diagnostic approach to the complexity of IgG4-related disease. Mayo Clin Proc 2015;90:927-39. Crossref

3. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732-8. Crossref

4. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30. Crossref

5. Chow TL, Chan TT, Choi CY, Lam SH. Kuttner’s tumour (chronic sclerosing sialadenitis) of the submandibular gland: a clinical perspective. Hong Kong Med J 2008;14:46-9.

6. Khurram SA, Fernando M, Smith AT, Hunter KD. IgG4-related sclerosing disease clinically mimicking oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:e48-e51. Crossref

7. Khosroshahi A, Wallace ZS, Crowe JL, et al. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol 2015;67:1688-99. Crossref

A 37-year-old Chinese woman was admitted to the First Affiliated Hospital, College of Medicine, Zhejiang University, China in July 2009 with pain in the upper back and hip for 9 months. She denied any chronic medication or illness. Her serum calcium level was 2.73 mmol/L (reference range [RR], 2.08-2.60 mmol/L), phosphorus 0.68 mmol/L (RR, 0.81-1.62 mmol/L), alkaline phosphatase 366 IU/L (RR, 30-115 IU/L), and intact parathyroid hormone (iPTH) 1154 pg/mL (RR, 12-65 pg/mL). T-score and Z-score for femoral bone mineral density were -2.7 and -2.8, respectively. Cervical computed tomography (CT) scan and thyroid, parathyroid, and abdominal (including pancreas, adrenals) ultrasonography were unremarkable. Anterior planar technetium (^99mTc) sestamibi (MIBI) scintigraphy images of the neck and chest showed a focal shadow with intense tracer uptake in the superior thorax at 15 minutes (Fig a) and 120 minutes (Fig b) following injection of ^99mTc-MIBI. Thoracic CT revealed a contrast-enhanced nodule with soft tissue density of 2.9 x 1.3 cm in the anterior mediastinum (Fig c). Thoracic and abdominal CT showed a brown tumour in the right omoplate, the fourth posterior left rib, and iliac bone (Figs d and e).

A mid-sternal thoracotomy was performed. A dark red mass of 4 x 2.4 x 1 cm was found in the thymus isthmus and resected. The mediastinal mass was covered with a thin fibrous capsule and on section showed a greyish cut surface. Histology confirmed the presence of ectopic parathyroid adenoma composed predominantly of oxyphil cells arranged in acinar pattern. Serum calcium level was 2.18 mmol/L and iPTH 17.2 pg/mL 16 hours after surgery. Hypocalcaemia (serum calcium, 1.68 mmol/L) and hungry bone syndrome occurred 3 days after surgery and gradually improved over a week with calcium carbonate and calcitriol supplementation that was started after surgery and continued thereafter. Serum calcium and iPTH remained normal after 5 years’ follow-up.

A diagnosis of primary hyperparathyroidism in a symptomatic patient is made in the presence of hypercalcaemia, hypophosphataemia, and raised levels of alkaline phosphatase and iPTH,1 as demonstrated in our case. Primary hyperparathyroidism occurs in approximately 1% of the adult population, commonly due to solitary parathyroid adenomas (85%).1 Primary hyperparathyroidism due to ectopic parathyroid adenomas can pose diagnostic and management challenges, especially when imaging studies provide limited sensitivity.2

The embryological origin of the parathyroid glands is the endoderm of the third and fourth pharyngeal pouches, from where these glands migrate to their usual position behind the thyroid gland. It is well known that parathyroid glands can be found in aberrant locations, mainly in the thyroid parenchyma or in the mediastinum.3 The high incidence of ectopic inferior parathyroid glands has been attributed to abnormal migration during embryogenesis. Since parathyroid glands lack capsular fixation, an ectopic parathyroid gland may also develop from a gland that is initially present in a normal anatomic position but which enlarges and is displaced to an ectopic location where there is little resistance.

Ultrasonography is commonly used to locate enlarged parathyroid glands due to its convenience and low cost. Its ability to detect abnormalities, however, depends on the experience and skill of the operator so sensitivity in the localisation of enlarged parathyroid glands varies greatly (44%-87%).2 Ectopic parathyroid adenomas may be detected with MIBI at a sensitivity level almost identical to that of orthotopic adenomas. Focal increased activity separated from the lower pole of the thyroid on MIBI images gives a high probability for locating ectopic parathyroid adenoma in the thymus. Of note, ^99mTc-MIBI is a non-specific tracer that is taken up by mitochondria so any mitochondria-rich cells may show uptake. Mitochondrial density in an adenoma is also a major factor that can cause prolonged retention of ^99mTc. This is evidenced by the number of mitochondrion in lesions detected by scintigraphy that is significantly higher than in those that are missed, with the highest ratio of mitochondria per cell found in oxyphil cells. The typical pattern in a parathyroid adenoma demonstrates a prolonged retention of ^99mTc-MIBI in the adenoma with rapid washout of the tracer from normal thyroid tissue. The degree of MIBI uptake in parathyroid adenomas has been reportedly correlated with the size of gland and the cytological composition (greater uptake seen in adenomas with dominance of oxyphil cells over chief cells).2

Of note, CT may further contribute to the identification of ectopic parathyroids and the differential diagnosis from other lesions. In our cases, the parathyroid glands were not located by ultrasonography although a combination of MIBI scintigraphy and CT imaging accurately localised the tumour in the anterior mediastinum. This highlights the usefulness of combining multiple imaging techniques to locate an ectopic active parathyroid gland. These combinations are cost-effective, and considered an approach to routine preoperative localisation of ectopic parathyroid adenomas, especially in cases with a negative MIBI scan.4

Hungry bone syndrome refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia following parathyroidectomy as a result of extensive remineralisation.5 Various risk factors of hungry bone syndrome include older age, large parathyroid adenoma, overt bone disease, and vitamin D deficiency. Consequently, transient hypocalcaemia is frequently encountered postoperatively; the presence of mild hypocalcaemia provides reassurance that the hyperactive adenomatous gland has been successfully removed.

For any hypercalcaemia and high level of PTH without parathyroid adenoma in the neck, physicians should remain alert and continue to search for ectopic locations using a combination of imaging techniques. The mediastinum must be cautiously explored since it is a very common location for ectopic parathyroid adenoma. The combination of several imaging techniques has an incremental effect on the localisation of ectopic parathyroid adenomas compared with use of either one technique alone.

1. AACE/AAES Task Force on Primary Hyperparathyroidism. The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract 2005;11:49-54. Crossref

2. Haber RS, Kim CK, Inabnet WB. Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m) technetium sestamibi scintigraphy. Clin Endocrinol (Oxf) 2002;57:241-9. Crossref

3. Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes 2012;120:604-10. Crossref

4. Elaraj DM, Sippel RS, Lindsay S, et al. Are additional localization studies and referral indicated for patients with primary hyperparathyroidism who have negative sestamibi scan results? Arch Surg 2010;145:578-81. Crossref

5. Witteveen JE, van Thiel S, Romijn JA, Hamdy NA. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol 2013;168:R45-53. Crossref

In March 2011, a 47-year-old Chinese woman who enjoyed good past health presented to a local general out-patient clinic in Hong Kong with a 2-week history of a mildly painful cord-like structure stretching from the inferior part of the left breast to the umbilicus level (Fig). She had worked as a dishwasher 3 months prior to the appearance of the lesion, a job that required her to carry stacks of heavy dishes. There was no recent trauma or surgery of the breast and no family history of breast cancer. Physical examination revealed a 15-cm long by 0.5-cm wide erythematous subcutaneous cord-like lesion stretching from the inferior part of the left breast down along the anterolateral chest wall to the umbilicus level. The lesion was firm and mildly tender. It was adherent to the skin, but was slightly movable over the deeper tissues. Examination of the breasts showed no asymmetry or skin changes. Palpation of the right breast was normal. There was, however, mild lumpiness over the outer upper quadrant of the left breast although no definite breast lump found. The nipples were normal with no discharge. There were no palpable axillary or regional lymph nodes.

The patient was diagnosed with Mondor’s disease with involvement of the thoracoepigastric vein. The course of the disease was explained and the patient was advised to avoid repetitive strain of the chest wall. Paracetamol was prescribed for symptomatic relief. She was referred to the Surgical Specialist Outpatient Clinic (SOPC) for further evaluation of left breast lumpiness. The cord in this patient disappeared spontaneously after approximately 5 weeks. Clinical assessment at the SOPC in May 2011 did not identify any palpable breast lump. Routine mammogram was later performed in August 2012 and revealed a 2-cm ill-defined high-density speculated lesion in the outer-upper quadrant of the left breast. Supplementary ultrasonography was also performed and revealed an ill-defined irregular hypoechoic lesion measuring 0.7 x 0.6 x 1.65 cm. The patient was followed up in the SOPC 2 weeks later and the lesion was also clinically palpable. Core biopsy confirmed invasive ductal carcinoma. Left modified radical mastectomy was performed with metastatic invasive ductal carcinoma and axillary lymph node involvement confirmed (stage pT1cpN1). The patient was also treated with adjuvant chemotherapy.

Mondor’s disease is an uncommon clinical condition of thrombophlebitis of the subcutaneous veins of the anterolateral thoracoabdominal wall. The most commonly affected vessels are the thoracoepigastric, lateral thoracic, and superior epigastric veins.1 It is characterised by sudden onset of one or more subcutaneous palpable and visible cord(s) over the mammary area, chest wall, or epigastrium.

Mondor’s disease occurs most commonly in middle-aged patients, and is more common in women than in men (ratio 3:1).2 The involved subcutaneous veins will initially turn red and tender and subsequently become a painless and tough fibrous band. Pathologically, the first stage is due to infiltration of inflammatory cells resulting in obliterative thrombophlebitis of the affected veins, causing redness and tenderness. In the second stage, connective tissues proliferate in the vessels with consequent formation of the fibrous band.1 Recanalisation of the veins occurs later and the fibrous band will disappear within several weeks.3

It is thought to be a very uncommon disease although the true incidence is unknown as it is self-limiting and patients may not seek medical attention. The diagnosis can usually be made based on clinical history and typical physical findings. Biopsy is not essential.

The aetiology of Mondor’s disease is still unclear. In many cases it is idiopathic, although it has also been linked with recent breast surgery, local trauma, excessive physical activity with muscle strain, an inflammatory process, infections, and mammary pathology including mastitis or abscess.2 Association with breast cancer has also been reported. Catana et al4 studied 63 cases of Mondor’s disease of whom eight (12.7%) had associated breast cancer. The authors suggested that mammography should be performed in patients with Mondor’s disease even when physical examination was normal. A retrospective review in 2011 identified five cases of Mondor’s disease of the breast; none of which was associated with breast cancer.5 Nonetheless, the authors advised thorough evaluation of the breast to exclude an underlying breast cancer. In our patient, the correlation with an occult carcinoma of the breast could not be confirmed since there was a time delay between the presentation of Mondor’s disease and the diagnosis of breast carcinoma. Moreover, the patient’s recent strenuous job with repetitive straining of the chest wall muscle might have been a predisposing factor.

Since Mondor’s disease is self-limiting, symptomatic treatment is suggested. General advice includes rest, local application of heat, and better breast support. Oral non-steroidal anti-inflammatory drugs provide effective symptomatic relief.2

In summary, Mondor’s disease is a condition that is rarely encountered in primary care. Recognising this condition is important as it can avoid unnecessary investigations and referral for diagnosis. Although the association of underlying breast cancer with Mondor’s disease has not been confirmed, family physicians should be aware of the possibility and conduct a thorough evaluation including clinical examination and imaging of the breast to exclude its presence in patients diagnosed with Mondor’s disease.

1. Alvarez-Garrido H, Garrido-Ríos AA, Sanz-Muñoz C, Miranda-Romero A. Mondor’s disease. Clin Exp Dermatol 2009;34:753-6. Crossref

2. Mayor M, Burón I, de Mora JC, et al. Mondor’s disease. Int J Dermatol 2000;39:922-5. Crossref

3. Ichinose A, Fukunaga A, Terashi H, et al. Objective recognition of vascular lesions in Mondor’s disease by immunohistochemistry. J Eur Acad Dermatol Venereol 2008;22:168-73.

4. Catana S, Zurrida S, Veronesi P, Galimberti V, Bono A, Pluchinotta A. Mondor’s disease and breast cancer. Cancer 1992;69:2267-70. Crossref

5. Salemis NS, Merkouris S, Kimpouri K. Mondor’s disease of the breast. A retrospective review. Breast Dis 2011;33:103-7. Crossref

An 18-year-old girl was admitted to the Aga Khan Hospital, Pakistan in April 2014 with progressively worsening shortness of breath, orthopnoea, malaise, and low-grade fever for 3 years, and generalised body swelling for 6 months. She had no significant medical history or trauma.

On physical examination she was a medium-built girl with a heart rate of 120 beats/min, raised jugular venous pressure, and bilateral pedal pitting oedema. Chest auscultation revealed muffled heart sounds with bilateral basilar lung crepitations. The chest X-ray showed wide mediastinum with clear lung markings.

The computed tomographic (CT) scan showed a conglomerate undefined mass in the anterior, middle, and posterior mediastinum encasing the entire heart and great vessels with most marked extension in the retrocardiac area (Fig 1). The echo showed a large echo-dense mass compressing the heart with invasion into the left atrium (LA), obliterating most of the LA cavity.

Video-assisted thoracoscopic surgery was performed and the mass biopsied for histopathological examination. The histopathology showed fibrosis and chronic granulomatous inflammation with fungal hyphae on periodic acid–Schiff staining (Fig 2). The fungal cultures grew Aspergillus flavus.

A diagnosis of invasive mediastinal aspergillosis was made and the patient was started on oral itraconazole 100 mg twice a day. She showed a remarkable recovery in her symptomatology in the first 6 weeks of follow-up.

Aspergillosis refers to a variety of diseases caused by several species of Aspergillus organisms that are abundant in the environment and recognition of which has increased over recent years. There are three main categories in general: saprophytic aspergilloma, allergic bronchopulmonary aspergillosis, and invasive aspergillosis. The term ‘invasive aspergillosis’ is generally used to imply a histopathologically demonstrated invasion of tissues by these spores. It represents an important cause of morbidity and mortality, particularly among immunocompromised patients, occurring mostly in those with haematological malignancies who are undergoing chemotherapy and organ transplantation with concomitant immunosuppressive therapy. Extension of invasive pulmonary aspergillosis to the mediastinum has been reported only rarely.1 Our case is an immunocompetent patient with extensive mediastinal aspergillosis who presented with dyspnoea and symptoms of cardiac tamponade.

Invasive aspergillosis varies in severity and clinical course, depending upon the affected organ and the host. It is caused by many Aspergillus groups; however the most common is the Aspergillus fumigatus group. These groups live in soil, and derive nutrients from dead plants and animal matter. It has been further subdivided in recent years to angioinvasive and airway-invasive aspergillosis. Invasive aspergillosis is a major cause of morbidity and mortality in immunosuppressed patients.2

The form that Aspergillus lung disease takes is heavily dependent on the immune response of the patient.3 Indolent forms of locally invasive aspergillosis in the form of chronic necrotising or semi-invasive aspergillosis in apparently immunocompetent individuals are now recognised.

Invasive aspergillosis is a result of three factors: (1) suppression of the immune response due to debilitating disease or therapy; (2) glucocorticoid therapy with consequent diminished inflammatory response and disruption of the normal flora by antimicrobial agents4; and (3) local implantation of the fungus. The disease is well known in immunocompromised individuals but has also been described in healthy individuals. Patients with a compromised immune system, specifically with neutropenia, are susceptible to acute airway-invasive and angioinvasive aspergillosis in the absence of pre-existing lung pathology.

There have been a few cases described in which patients were immunocompetent. Orr et al5 documented two patients with normal host defences in whom postmortem examination revealed death due to disseminated aspergillosis (one patient had a history of coronary heart disease, the other acute renal failure following gangrenous appendicitis). Our patient was otherwise healthy as confirmed by the normal haematological studies.

The usual pathogenesis of invasive aspergillosis is by dissemination from a primary site, such as the lungs or the paranasal sinuses, or by contiguous spread.6 In this particular patient, the chest X-ray and CT scan of the chest were clear without a primary lesion. It was therefore postulated that inhalation of the fungal spores with immediate mediastinal invasion resulted in the implantation of a high concentration of aspergillus spores around the heart. This was followed by chronic infiltration around the pericardium and extension into the heart.

This idea was supported by the histopathology report of granulomatous tissue fibrosis, indicating a long-standing process, and in keeping with the history of worsening shortness of breath for 3 years. Our case showed an undefined mass in the anterior, middle, and posterior mediastinum extending into the LA. The effects of the mass could explain all of the patient’s symptoms, namely worsening dyspnoea and cardiac tamponade symptoms.

In conclusion, this case highlights that there is usually a long dormant period before the clinical manifestation of aspergillosis, clinically and radiologically the disease may be suggestive of a malignant process, and contamination with aspergillus should be considered from all possible aspects, particularly in healthy individuals.

1. Shakoor MT, Ayub S, Ayub Z, Mahmood F. Fulminant invasive aspergillosis of the mediastinum in an immunocompetent host: a case report. J Med Case Rep 2012;6:311. Crossref

2. Al-Alawi A, Ryan CF, Flint JD, Müller NL. Aspergillus-related lung disease. Can Respir J 2005;12:377-87. Crossref

3. Gefter WB. The spectrum of pulmonary aspergillosis. J Thorac Imaging 1992;7:56-74. Crossref

4. Mashimoto H, Suyama N, Araki J, et al. A case of mediastinitis and bilateral pyothorax, following acute epiglottitis with concurrent Aspergillus infection [in Japanese]. Kansenshogaku Zasshi 1992;66:648-52. Crossref

5. Orr DP, Myerowitz RL, Dubois PJ. Patho-radiologic correlation of invasive pulmonary aspergillosis in the compromised host. Cancer 1978;41:2028-39. Crossref

6. Hendrix WC, Arruda LK, Platts-Mills TA, Haworth CS, Jabour R, Ward GW Jr. Aspergillus epidural abscess and cord compression in a patient with aspergilloma and empyema. Survival and response to high dose systemic amphotericin therapy. Am Rev Respir Dis 1992;145:1483-6. Crossref