In December 2016, a 47-year-old Chinese woman was referred to our clinic for treatment of a large cystic pancreatic lesion. She presented with a 12-month history of intermittent epigastric pain associated with eating and weight loss of 5 kg. The patient had a history of uterine fibroids and underwent myomectomy 10 years previously. She was also under observation for a benign thyroid nodule. She had no family history of malignancy, denied consumption of alcohol, was a non-smoker, and lived as a housewife.

A contrast-enhanced computed tomography scan of the abdomen revealed a cystic neoplasm 8 cm in diameter involving the head, neck, and body of the pancreas, with proximal dilatation of the pancreatic duct (Fig 1). Based on the patient’s symptoms and the size of the lesion, surgical resection was recommended. Preoperative laboratory test results, including full blood count, liver and renal function tests, blood glucose level, amylase, carcinoembryonic antigen, and cancer antigen 19.9, were within normal limits.

During surgery, a multiloculated cystic lesion was identified (Fig 2). The cystic content was serous. No nearby enlarged lymph nodes or tissue invasion suggestive of frank malignancy were evident. The pancreatic tail was healthy. An extended middle pancreatectomy (EMP) was performed. The patient recovered without complication and was discharged from hospital 13 days after surgery. Histological examination of the resected tissue confirmed a benign serous cystadenoma.

A bilateral subcostal incision was made. The lesser sac was entered to expose the anterior aspect of the pancreas after division of the gastrocolic ligament (Fig 2a). The gastroduodenal junction was purposefully divided to gain better exposure of the large cystic lesion and to facilitate further pancreatic dissection (Fig 2b). The posterior peritoneum along the inferior and superior margins of the pancreas was dissected. The superior mesenteric vein was identified under the neck of the pancreas. The splenic vein was carefully divided away from the gland and all the small branches of the pancreas draining into the splenic vein were ligated. The gallbladder was removed to facilitate identification and mobilisation of the common bile duct, the hepatic artery, and the portal vein from above. The involved portion of the pancreas was mobilised on both cephalic and caudal sides. The cystic tumour was resected in its entirety with a margin by scalpel and cautery. Most of the head (estimated 80%-90%), neck, and body of the pancreas were removed (Fig 2c). The remaining pancreatic head stump was carefully over-sewn with 3-O Prolene sutures (Ethicon; Cornelia [GA], United States) to avoid pancreatic leak. The pancreatic duct opening was identified and separately sutured. The stump was further re-enforced with fibrin sealant, Tisseel glue (Baxter Healthcare, Deerfield [IL], United States). The distal side stump was anastomosed into a Roux loop of jejunum using an end-to-end technique with invagination (Fig 2d). A short segment of catheter was inserted into the pancreatic duct. The gastric pylorus was then joined up to the proximal jejunum as a gastrojejunostomy and a jejunojejunostomy was fashioned to prevent bile reflux. The proximal jejunum was reconnected to the jejunal Roux loop distally. Two drainage tubes were placed close to the closed cephalic stump and the pancreaticojejunostomy anastomosis before proceeding with abdominal wound closure.

For benign or low-grade malignant lesions of the pancreatic neck and body, traditional approaches for surgical resection include a pancreaticoduodenectomy (PD) or an extended distal pancreatectomy. Enucleation is suitable only for small and superficial lesions that do not have any connection with the pancreatic duct. In 1957, Guillemin and Bessot first reported the technique of middle pancreatectomy (MP) for chronic pancreatitis and pancreatic transection injury.1 In 1982, Dagradi and Serio proposed the use of MP for resection of benign tumours or tumours with low malignant potential situated in the pancreatic neck and body.2 The technique has since gained acceptance.

In this case, the large cystadenoma involved a significant portion of the head of the pancreas in addition to the neck and the body. Traditional approaches for resection of such a lesion would involve either subtotal pancreatectomy or PD. The MP technique described in the literature has not included resection of the head of the pancreas. However, in this case, most of the pancreatic head in addition to the neck and the body of pancreas had to be resected. Therefore, the procedure is being formally named for the first time, EMP.

Extended middle pancreatectomy permits resection of a lesion that extends into the head of the pancreas while conferring similar advantages of an MP over traditional approaches. Compared with other surgical options (subtotal pancreatectomy and PD), this confers the advantage of parenchymal preservation and consequent preservation of pancreatic exocrine and endocrine functions.3 Pancreaticoduodenectomy has been associated with increased postoperative morbidity and mortality. Similarly, the inability to preserve the spleen in subtotal pancreatectomy has been associated with complications of thrombosis and susceptibility to infection. Finally, MP has been associated with a higher incidence of pancreatic fistula, compared with PD and extended distal pancreatectomy procedures.4 5 This has been attributed to the need to manage two pancreatic remnants by anastomosis or closure. However, as much less pancreatic head tissue is left behind in EMP, the risk of pancreatic leak from the proximal stump should theoretically be lower than that observed in MP.

We report, to the best of our knowledge, the first clinical case of EMP in the management of a large cystic neoplasm. This case demonstrated excellent postoperative outcomes and suggests that EMP may be considered a viable preferred surgical option in selected cases. However, the technical difficulties of this procedure should not be underestimated. The long-term functional outcomes have yet to be substantiated by further clinical experience.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

As an Editor of the Journal, AKK Chui was not involved in the peer review process. The other authors have disclosed no conflicts of interest.

This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the tenets of the Declaration of Helsinki. Patient consent was obtained.

1. Guillemin P, Bessot M. Chronic calcifying pancreatitis in renal tuberculosis: pancreatojejunostomy using an original technic [in French]. Mem Acad Chir (Paris) 1957;83:869-71.

2. Dagradi A, Serio G. Pancreatectomia intermedia. In: Enciclopedia Medica Italiana. Pancreas, vol XI. Florence: USES Ed Scientifiche; 1984: 850-1.

3. Tan Z, Chen P, Dong Z, Zhou B, Guo WD. Clinical efficacy of middle pancreatectomy contrasts distal pancreatectomy: a single-institution experience and review of literature. ANZ J Surg 2019;89:E184-9. Crossref

4. Shibata S, Sato T, Andoh H, et al. Outcomes and indications of segmental pancreatectomy. Comparison with distal pancreatectomy. Dig Surg 2004;21:48-53. Crossref

5. Du ZY, Chen S, Han BS, Shen BY, Liu YB, Peng CH. Middle segmental pancreatectomy: a safe and organ-preserving option foe benign and low-grade malignant lesions. World J Gastroenterol 2013;19:1458-65. Crossref

A 62-year-old man with no known systemic disease was brought to an emergency department by ambulance. He was found trapped in a car after colliding with a bridge and was found to have been driving under the influence of alcohol. On arrival, he complained of headache, neck pain, and chest pain. Physical examination revealed blood pressure of 133/71 mm Hg, heart rate 71 beats per minute, respiratory rate 22 breaths per minute, and oxygen saturation on air of 93%. He appeared intoxicated and was disorientated with a score of 13 (E3V4M6) on the Glasgow Coma Scale. His pupil size was 3.5 mm with bilateral normal reaction to light. A thorough neurological examination could not be performed but the patient was able to move all four limbs without limitation. Nonetheless a scalp laceration, upper back tenderness and left lower cervical crepitus were evident during palpation. Chest examination revealed bilateral equal breath sounds but some basal crackles and a left flank abrasion about 3 × 4 cm in size. Haemogram and biochemistry test results were within normal limits but serum alcohol level was elevated at 2.48 g/L. Chest radiography revealed a posterior fracture at the left fourth to sixth ribs and right ninth rib as well as left cervical subcutaneous emphysema that raised the suspicion of barotrauma associated with chest trauma (Fig 1). In view of the possibility of barotrauma and intracranial injuries, further evaluation with computed tomography (CT) of the brain and chest was arranged. The former was normal and the latter confirmed right first to second posterior ribs and left third to sixth posterior ribs fractures, as well as a small left-sided pneumothorax, bilateral pulmonary contusions, and pneumomediastinum. Notably, free air accumulated in the posterior epidural spaces of the cervical and thoracic spine as well as in the left retrospinal and paraspinal muscle layers with accompanying left second and third thoracic spine posterior neural arch fracture in cervical spine CT scan (Fig 2); these findings were compatible with epidural pneumorrhachis. Additionally, air was seen dissecting from the posterior neck into the epidural space. A neurosurgeon recommended close observation rather than surgical intervention for both the epidural pneumorrhachis and thoracic spine fracture. The patient was admitted to the thoracic surgical ward where he received conservative therapy for rib fractures, pneumothorax and pneumomediastinum including meperidine for pain control and oxygen therapy via a nasal cannula at 3 L/min. New chest radiographs were taken on day 4 after surgery. Cervical emphysema had mostly resolved but there was progression of pulmonary contusion with bilateral minimal pleural effusions. The patient also exhibited wheezing and dyspnoea that warranted inhaled bronchodilators and systemic steroid therapy. The patient was discharged on day 12 after surgery with symptom improvement; no neurological sequelae were noted during follow-up at the out-patient department.

Pneumorrachis (PRS) is characterised by the presence of air within the spinal canal and can be classified according to its location as subarachnoid or epidural PRS. Each is associated with different pathophysiological mechanisms and causes. It may result non-traumatically from spinal degeneration, gas-producing infections, or spontaneous pneumomediastinum in patients with asthma. Iatrogenic PRS may occur following a surgical procedure, epidural anaesthesia, or lumbar puncture but PRS following trauma is rare.1 Almost all types of PRS are found in association with air distribution in other compartments and cavities of the body. For example, PRS is observed in conjunction with pneumocephalus, pneumothorax, pneumomediastinum, pneumopericardium, or subcutaneous emphysema. Pneumorrachis following trauma is rare and arises from the presence of air in the posterior mediastinum or retropharyngeal space dissecting along the fascial planes from the posterior mediastinum or retropharyngeal space through the neural foramina into the epidural space under the driving pressure of a pneumothorax and pneumomediastinum and low resistance of loose connective tissue.2

Epidural PRS has been reported to occur most commonly secondary to traumatic pneumomediastinum. Neurological deficits have not been reported in epidural PRS secondary to trauma. In contrast, traumatic subarachnoid PRS is almost always secondary to major trauma and skull bone fractures, and indicates severe injury and possible association with complications such as tension pneumocephalus or meningitis.3 Various neurological deficits, such as acute lumbar root compression, chronic radiculopathy, and cauda equina syndrome may occur. It is therefore important to identify air in the epidural space and subarachnoid space to enable prompt and adequate management.4 The possible mechanism of PRS in our patient was air entry into the epidural space because of pneumomediastinum, left-sided pneumothorax and subcutaneous emphysema extending through the fractured neural arch of the thoracic spines into the epidural space; these conditions fulfil the criteria for benign traumatic PRS. Criteria for a diagnosis of benign traumatic epidural PRS include substantial pneumomediastinum with extensive subcutaneous emphysema due to thoracic trauma.4 There may also be incidental findings of small amounts of epidural air demonstrable only on CT and unrelated to spinal trauma. “Benign” epidural PRS can be managed conservatively with spontaneous resolution of epidural air.4 Repeat or further neuroimaging studies are not routinely provided in cases of epidural PRS, provided there is no new or progressive neurological deficit. Three cases have been reported with complete resolution of PRS on follow-up CT scan after 4 to 14 days.5 6 7

The PRS is usually asymptomatic and an accidental finding on CT images while evaluating other severe or life-threatening torso injuries. Although CT is the gold standard for diagnosis, it is difficult to differentiate epidural and subarachnoid PRS. Nonetheless in the former, air is collected at the corner or peripherally unlike subarachnoid PRS where it is distributed more centrally in the canal based on normal anatomy. Magnetic resonance imaging or intrathecal contrast CT can distinguish intradural from extradural air.7 In most cases of epidural PRS, the air reabsorbs spontaneously without recurrence and the patient can be managed conservatively.1 In subarachnoid PRS, timely consultation with a neurosurgeon for decompression of nerve root injuries, tension pneumocephalus and exploratory surgery by a chest surgeon to detect severe thoracic trauma is vital. Impressively, Avci et al5 reported a case of complete resolution of subarachnoid PRS on the fifth day of admission with recovery of neurological deficit after chest tube insertion. They concluded that the negative pressure of the chest drain to withdraw the air supported the hypothesis of a one-way valve mechanism in which high pressure air travels through fascial layers but is unable to return. The routine use of antibiotic is not recommended in either type unless meningitis develops.1

Traumatic PRS is rare and an incidental radiological finding. Epidural PRS is often self-limiting with a good prognosis. Although most patients can be managed conservatively, prompt recognition of subarachnoid PRS with neurological deficits and other concurrent life-threatening torso injuries is vital.

Concept or design: KH Lee.
Acquisition of data: YY Yang.
Analysis or interpretation of data: CB Chua.
Drafting of the manuscript: YY Yang and KH Lee.
Critical revision of the manuscript for important intellectual content: CW Hsu.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

We would like to extend our special thanks to Dr Cheng-yang Lee, Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan who provided insight and expertise on the image interpretation that greatly improved our manuscript.

All authors have no commercial association, such as consultancies, stock ownership or other equity interests or patent-licensing arrangements.

The patient was treated in accordance with the tenets of the Declaration of Helsinki. The patient provided written informed consent for all treatments and procedures.

1. Oertel MF, Korinth MC, Reinges MH, Krings T, Terbeck S, Gilsbach JM. Pathogenesis, diagnosis and management of pneumorrhachis. Eur Spine J 2006;15 Suppl 5:636-43. Crossref

2. Defouilloy C, Galy C, Lobjoie E, Strunski V, Ossart M. Epidurual pneumatosis: A benign complication of benign pneumomediastinum. Eur Respir J 1995;8:1806-7. Crossref

3. Goh BK, Yeo AW. Traumatic pneumorrhachis. J Trauma 2005;58:875-9. Crossref

4. Willing SJ. Epidural pneumatosis: a benign entity in trauma patients. AJNR Am J Neuroradiol 1991;12:345.

5. Avci İ, Başkurt O, Şirinoğlu D, Aydin MV. Rapid disappearance of pneumorrhachis after chest tube placement. Turk J Emerg Med 2019;19:146-8. Crossref

6. Kim SW, Seo HJ. Symptomatic epidural pneumorrhachis: a rare entity. J Korean Neurosurg Soc 2013;54:65-7. Crossref

7. Pfeifle C, Henkelmann R, von der Höh N, et al. Traumatic pneumorrhachis. Injury 2020;51:267-70. Crossref

A 61-year-old man with end-stage renal failure secondary to immunoglobulin A nephropathy underwent a cadaveric kidney transplant. His post-transplantation course was uneventful until he had very poor compliance to the immunosuppressants since May 2017 and admitted that he had stopped all immunosuppressants in February 2018. He developed acute antibody-mediated graft rejection in May 2018. His medications were adjusted, tacrolimus 4 mg/day, mycophenolate 360 mg twice daily and prednisolone were started. He developed a chest infection in October 2018. He denied any travel history or significant contact history. On physical examination he had cushingoid features and right-sided crepitation. Investigations revealed a low white cell count (1.8 × 10⁹/L) and neutrophil count (0.7 × 10⁹/L). Chest X-ray showed right basal infiltrates (Fig 1a). Blood and sputum for bacterial culture was negative, as was sputum for acid-fast bacilli. The patient’s condition deteriorated despite use of vancomycin, meropenem, azithromycin, and fluconazole. Computed tomography of the thorax revealed extensive collapse and consolidation over the right lower lobe and bilateral pleural effusions (Fig 1b). Bronchoscopy and transbronchial lung biopsy showed granulomatous inflammation, with granular eosinophilic material and narrow-based small budding yeasts grouped in clusters inside macrophages in the alveolar spaces. Both mucicarmine staining and immunohistochemical staining for Pneumocystis, Cytomegalovirus, and herpes simplex virus were negative (Fig 1d-g). In view of the histopathological findings, bronchoalveolar lavage was sent for fungal culture. After 7 days of incubation at 25°C, a tiny colony of mould was seen. 21 Days later, there was a white-coloured mould colony with a velvety texture, wrinkled surface, acquired splits on the surface with no diffusible pigment (Fig 2a and b). Lactophenol cotton blue stain of the wet mount revealed a classic floret pattern (Fig 2c and d). Subculture was performed at 35°C. After 10 days of incubation at 35°C, a 25-mm-diameter yeast colony was evident. Based on the characteristic growth morphology, infection with the thermally dimorphic fungus was established. Subsequent molecular genetic analysis by sequencing of the internal transcribed spacer and D1/D2 regions was performed and identified Emergomyces pasteurianus, a rare thermally dimorphic fungus not previously reported in our locality. Liposomal amphotericin B was commenced and continued for 8 weeks. The patient responded well both clinically and radiologically (Fig 1c) and treatment was switched to oral voriconazole 200 mg twice daily. The patient succumbed to his medical illness 10 weeks after being discharged home.

Thermally dimorphic fungal pathogens cause a significant human disease but are rarely reported in our locality with the exception of Talaromyces (Penicillium) marneffei. To the best of our knowledge, this is the first report of Emergomyces infection in Hong Kong. Emergomyces shares the characteristics of other thermally dimorphic fungi: filamentous forms at 25°C that becomes an invasive yeast-like form at 35°C.1 Emergomyces pasteurianus was previously known as Emmonsia pasteuriana. Emmonsia species are ubiquitous, soil-dwelling saprophytic fungi. Species such as Emmonsia crescens and Emmonsia parva may rarely cause adiaspiromycosis in rodents and humans.2 Recently, Emergomyces has been reclassified as a new genus within the family Ajellomycetaceae. Emergomyces and Emmonsia have significant differences in microbiology, epidemiology, clinical manifestations, and treatment outcomes. Microbiologically, Emergomyces is a thermally dimorphic fungus while Emmonsia does not undergo mould-to-yeast conversion at 37°C. Emmonsia is rarely cultivated from clinical specimens. Human infection with Emmonsia is relatively rare in clinical practice2 but Emergomyces can cause fatal and disseminated human infection and appropriate antifungal therapy is essential.

At the time of this report, five Emergomyces species are described. These species differ in geographic distribution. Es pasteurianus has been reported in Europe, Asia, and Africa. Emergomyces canadensis has been reported in Canada and the United States. Emergomyces africanus has been reported in South Africa, Emergomyces orientalis in China, and Emergomyces europaeus in Germany. The natural reservoir of Emergomyces is soil. Our patient presumably acquired the infection via inhalation of conidia in Hong Kong since he had no travel history outside of the region.

Emergomycosis is a multi-system disease. According to case reports, patients most often present with fever, widespread skin lesions, weight loss, and pulmonary disease.3 4 The diagnosis can be missed due to the slow-growing nature of the fungus. Histological examination of tissues can help diagnose the disease but on its own does not distinguish infection from other dimorphic fungi. Molecular diagnosis plays an important role in microbiological investigation. Using broad-range fungal polymerase chain reaction to sequence D2 large-subunit rDNA gene can help to confirm the diagnosis in a rapid, sensitive, and specific way.

There are no treatment guidelines for patients with emergomycosis. Guidelines for blastomycosis and histoplasmosis recommend liposomal amphotericin B as initial therapy followed by itraconazole (or other newer azole). Our patient responded to liposomal amphotericin B and oral voriconazole but passed away due to his medical disease.

More patients are now rendered immunosuppressed by advances in treatment for a variety of diseases. Clinicians and microbiologists should be aware of the presence of rare invasive fungal infections among these susceptible patients. Molecular techniques such as internal transcribed spacer polymerase chain reaction and sequencing can aid early and accurate identification of these rare fungal pathogens.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

The authors have no conflicts of interest to disclose.

The authors would like to thank pathologist Dr WL Lam for providing the histopathology clinical photos and nephrologist Dr SK Fung and Dr HL Tang for providing clinical information.

This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This case report was approved by the Hospital Authority Kowloon West Cluster Research Ethics Committee (Ref KW/ EX-19-063(137-04)).

1. Gast KB, van der Hoeven A, de Boer MG, et al. Two cases of Emergomyces pasteurianus infection in immunocompromised patients in the Netherlands. Med Mycol Case Rep 2019;24:5-8. Crossref

2. Koneru H, Penupolu S. Pulmonary adiaspiromycosis: an emerging fungal infection. Chest 2017;152 Suppl:A162. Crossref

3. Schwartz IS, Sanche S, Wiederhold NP, Patterson TF, Sigler L. Emergomyces canadensis, a dimorphic fungus causing fatal systemic human disease in North America. Emerg Infect Dis 2018;24:758-61. Crossref

4. Schwartz IS, Maphanga TG, Govender NP. Emergomyces: a new genus of dimorphic fungal pathogens causing disseminated disease among immunocompromised persons globally. Curr Fungal Infect Rep 2018;12:44-50. Crossref

The patient was a 60-year-old woman with a 14-year history of type 2 diabetes mellitus and dyslipidaemia with a complication of background diabetic retinopathy. In December 2016, during a routine follow-up examination, the patient was found to have asymptomatic 5-fold rise in liver aminotransferases. The patient’s glycosylated haemoglobin level was 8.5% and her low-density lipoprotein cholesterol (LDL-C) level was 2.0 nmol/L. She was taking metformin 500 mg 3 times daily, gliclazide 160 mg and vildagliptin 50 mg twice daily, and atorvastatin 20 mg once daily. In view of the possibility of statin-related hepatotoxicity, atorvastatin was withheld after 22 months of treatment. However, transaminitis persisted over the following 6 months after exclusion of viral hepatitis and any structural abnormality. After 2 months, the patient complained of bilateral thigh weakness (Medical Research Council grade 4/5) and myalgia that prevented her from climbing stairs. Blood tests revealed elevated levels of creatinine kinase (CK) [5426 IU/L; normal range, 26-192 IU/L], alanine aminotransferase (294 IU/L; normal range, <47 IU/L), aspartate aminotransferase (164 IU/L; normal range, <36 IU/L), and lactate dehydrogenase (722 IU/L; normal range, 110-210 IU/L). Other inflammatory markers for myositis including anti-Jo-1 antibodies were normal. Urine for myoglobulin was negative and renal function was normal. With persistent clinical and biochemical abnormalities 9 months after statin cessation and no history of potential drug or health products that might induce myositis, immune-mediated necrotising myopathy (IMNM) associated with statins was suspected. Electromyography suggested active myopathic changes while muscle biopsy revealed atrophy of multiple muscle fibres, necrosis and regeneration without inflammatory infiltrates. Diagnosis was finally confirmed following an enzyme-linked immunosorbent assay by a marked elevation of anti–3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR) autoantibody to >200 IU/mL (normal range, <20 IU/mL). Considering her reasonable glycaemic control, monotherapy with intravenous immune globulin (IVIG) was initiated at a rate of 2 g per kilogram body weight per month. Muscle power increased and CK decreased (Fig) so IVIG was stopped after 6 months. Nonetheless her muscle weakness worsened and extended to involve the upper limbs as well as her ability to swallow, and CK rose from 3200 IU/L to almost 8000 IU/L after 2 months. High-dose glucocorticoids (intravenous methylprednisolone 500 mg/day for 3 days followed by oral prednisolone 45 mg/day) and cyclosporin were started. A monthly IVIG infusion was also added in the initial 2 months to enhance the therapeutic effect for her severe myopathy. After 4 months, her weakness improved and CK dropped below 1000 IU/L. Owing to deteriorating glycaemic control (glycosylated haemoglobin level deteriorated to 9.1%) and acute glaucoma, early tapering of glucocorticoid dose was considered. However, serum CK level returned to 2000 IU/L when prednisolone dose was weaned down to 7.5 mg daily, although she retained full muscle power. Another steroid-sparing agent, either methotrexate or rituximab, was considered.

Statins are well-proven lipid-lowering drugs that reduce LDL-C and hence cardiovascular morbidity and mortality, in both primary and secondary prevention. Their use is recommended in a wide range of patients and high intensity therapy (LDL-C reduction ≥50%) is indicated in a significant proportion.1

Despite their acceptable side-effect profile, about 10% of patients report statin-associated muscle symptoms (SAMS) such as myalgia and/or weakness.2 Toxic myopathy, defined as SAMS with marked elevation (>10 times the upper limit of normal) of CK, occurs in approximately 1 in 10 000 patients treated with statins per year. Typically, this condition remits spontaneously with cessation of statin use. On the contrary, statin-associated IMNM, a rarer adverse effect with an estimated occurrence of 2 to 3 per 100 000 treated patients, is unlikely to be resolved by statin withdrawal, despite having similar SAMS and muscle enzyme increment.3 The IMNM was only suspected in our case 9 months after cessation of statin therapy, probably due to an initial lack of SAMS and misinterpretation that the elevated aminotransferases originated from the liver rather than muscle. It is important to also check CK in asymptomatic statin users with elevated aminotransferase levels to enable early diagnosis of statin-associated myopathy.

The IMNM is now recognised as a distinct form of myositis, usually presenting with symmetrical proximal arm or leg weakness with marked elevation of CK (>10 times the upper limit of normal), muscle oedema, and atrophy on magnetic resonance imaging. In addition, muscle cell necrosis and regeneration along with minimal inflammatory infiltrates in muscle biopsy is evident and irritable myopathy on electromyography.3 Our patient had clinical features compatible with most of these symptoms. Unlike other SAMS phenotypes, there are no identifiable risk factors such as lipophilic (vs hydrophilic) statins, high-dose statins, old age, female gender, small body frame, liver or renal failure, and concomitant medications metabolised by the same hepatic P450 isoforms2 in statin-associated IMNM (Table). The detection of anti-HMGCR autoantibody in 2010 revolutionised the pathophysiology, diagnosis, disease classification, and treatment of this disease entity. This autoantibody detected by means of an enzyme-linked immunosorbent assay is both sensitive and specific; it has been detected in 24 of 26 patients (92%) with a clinical presentation compatible with statin-associated IMNM although it has not been detected in statin-treated patients who do not have SAMS or self-limiting toxic myopathy. The overall specificity of the commercial enzyme-linked immunosorbent assays for anti-HMGCR autoantibody may be as high as 99.3%.4 Nevertheless anti-HMGCR autoantibodies can also be detected in patients with IMNM who have an underlying malignancy or who are statin-naïve, particularly with more widespread use of anti-HMGCR autoantibody in patients with myopathy. With the detection of another autoantibody against a signal recognition particle, in 2017 the European Neuromuscular Centre classified IMNM into three subtypes: anti–signal recognition particle myopathy, anti-HMGCR myopathy and antibody-negative IMNM.3 Although these subtypes share similar clinical features to those mentioned above, they differ in environmental risk factors, genetic risk factors, cancer risks, extra-muscular manifestations, and response to different treatment modalities and prognoses.

Although spontaneous improvement after statin cessation has been reported in case studies, most patients with this condition require one to two immunosuppressive agents, usually in the form of high-dose glucocorticoids plus one of the following; methotrexate, azathioprine, mycophenolate mofetil or cyclosporine, for initial disease control.4 5 The IVIG has also been used successfully as first-line monotherapy and it may be considered in those with pre-existing diabetes, as in our patient.6 However, incomplete normalisation of CK and the need for a prolonged course of treatment suggests its inability to completely abolish the pathophysiological process that causes muscle damage. This was illustrated in our patient with a rebound in CK level 2 months after completion of a 6-month course of IVIG monotherapy. Rather, her condition stabilised following treatment with two immunosuppressants, prednisolone and cyclosporine, although her anti-glycaemic treatment needed to be intensified. Similar to the clinical course of other reported series, her condition relapsed upon weaning of glucocorticoid dosage.7 Apart from escalation of steroid dosage, other steroid sparing agents may need to be considered. Rituximab has emerged as a promising rescue agent in this situation.8 Lastly, as statin is a known trigger of anti-HMGCR autoantibody, re-challenge with any statin should be avoided and an alternative cholesterol-lowering agent such as ezetimibe or PCSK9 inhibitors can be considered.9

In conclusion, IMNM can occur rarely in patients who present with SAMS. Unlike toxic myopathy, clinical and biochemical abnormalities persist upon statin withdrawal and immunosuppressants are usually required for disease control.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This case report received no specific grant from any funding agency in the public, commercial or not-for-profit sectors

The patient was treated in accordance with the Declaration of Helsinki. The patient provided written informed consent for all treatments and procedures.

1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082-143. Crossref

2. Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res 2019;124:328-50. Crossref

3. Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Immune-mediated necrotizing myopathy. Curr Rheumatol Rep 2018;20:21. Crossref

4. Mammen AL. Statin-associated autoimmune myopathy. N Engl J Med 2016;374:664-9. Crossref

5. Tiniakou E, Christopher-Stine L. Immune-mediated necrotizing myopathy associated with statins: history and recent developments. Curr Opin Rheumatol 2017;29:604- 11. Crossref

6. Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med 2015;373:1680-2. Crossref

7. Ramanathan S, Langguth D, Hardy TA, et al. Clinical course and treatment of anti-HMGCR antibody– associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflamm 2015;2:e96. Crossref

8. Allenbach Y, Mammen AL, Benveniste O, Stenzel W; Immune-Mediated Necrotizing Myopathies Working Group. 224th ENMC International Workshop: Clinicosero- pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul Disord 2018;28:87-99. Crossref

9. Albayda J, Christopher-Stine L. Identifying statinassociated autoimmune necrotizing myopathy. Cleve Clin J Med 2014;81:736-41. Crossref

Tissue diagnosis of pulmonary nodules of an undetermined nature can be achieved with thoracoscopic wedge resection. However, localisation of a lesion during surgery can be technically demanding, especially for small deep-seated lesions. We report our technique of indocyanine green (ICG) fluorescence-guided pulmonary wedge resection in a child.

A 4-year-old boy presented with pyrexia of unknown origin associated with cough for 2 weeks. Extensive septic workup including sputum culture, chest X-ray, nasopharyngeal aspirate and urine culture were unremarkable. Mantoux test was positive. Computed tomographic (CT) scan of the thorax to look for occult chest infection showed features suggestive of pulmonary tuberculosis and a 6-mm nodule over the apical segment of the left lower lobe. He completed a 6-month course of antitubercular medication but reassessment scan after 9 months showed a persistent left lower lobe pulmonary nodule and he was referred to our surgical unit for tissue diagnosis.

The patient underwent CT-guided localisation of the pulmonary nodule under general anaesthesia 1 hour prior to thoracoscopic wedge resection. The pulmonary nodule was identified at the apical segment of the left lower lobe, 1.3 cm from the pleural surface (Fig 1). An 18-gauge guiding needle was inserted by the radiologist to the lesion under CT guidance. Methylene blue (0.5 mL) and ICG (0.5 mL) were injected around the lesion via the guiding needle. A hookwire was also placed for localisation as safety backup and adjunct to ICG. The patient was then transferred back to the operating theatre. The target lesion was identified thoracoscopically with guidance of methylene blue dye and ICG fluorescence (KARL STORZ OPAL1®). Wedge resection of the target lesion was performed with Endo GIA™ Ultra Universal 30-mm staplers (Medtronic). Complete excision was confirmed by absence of fluorescence in the remaining left lower lobe on ICG fluorescence imaging (Fig 2). The use of ICG fluorescence enhanced intra-operative localisation of the small pulmonary nodule and facilitated a minimally invasive operation. The patient made an uneventful recovery and was discharged 2 days after surgery. Histology of the wedge-resected specimen confirmed complete excision and showed granulomatous inflammation with focal necrosis and no evidence of malignancy. The patient had resumed full activity at follow-up 1 week after surgery.

Intra-operative localisation of small pulmonary nodules remains a challenge for prompt and complete resection of lesions. It is recommended that preoperative localisation should be performed prior to minimally invasive resection for pulmonary nodules <10 mm in diameter or >5 mm from the pleural surface.1 Various means of preoperative localisation have been reported in children including micro-coil insertion, methylene blue dye injection, and radiotracer labelling.2 Hookwire is reported to be safe and useful for localisation of lung nodules in children as well as other situations such as thoracoscopic resection of deep-seated congenital cystic adenomatoid malformation.2 3 Although these methods are considered feasible in children, they have their own limitations and risks, such as local trauma and issues of inaccuracy in small lesions for hookwire localisation; difficulty in revealing deep lesions and diffuse spillage in small lesions of methylene blue dye. Efforts have been made to find a convenient, safe, and clear method for localisation.

The United States Food and Drug Administration has recently extended the approved uses of ICG to include sentinel lymph node biopsy in various types of tumour, assessment of blood supply in anastomosis and reconstructive flaps and enhanced visualisation of biliary anatomy during laparoscopic cholecystectomy.4 In thoracic surgery, it is a useful aid to sentinel lymph node mapping, lung mapping, oesophageal conduit vascular perfusion, and lung nodule identification.5 To date, no data about the use of ICG in thoracoscopic wedge resection in paediatric patients have been reported. In our experience, ICG preoperative localisation is a safe and feasible means to help achieve prompt and complete thoracoscopic wedge resection of small pulmonary nodules. It appeared to be more accurate than hookwire localisation in this patient, allowing immediate clear visualisation when guiding the extent of resection. It also facilitated easy assessment of completeness of resection.

In conclusion, ICG fluorescence is a safe and feasible method of localisation prior to thoracoscopic wedge resection of a pulmonary nodule in children.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

As an editor of the journal, KKY Wong was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. The patient provided written informed consent for all procedures.

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