Therapeutic Response to PRRNT in a Rare Case of Metastatic Renal Neuroendocrine Carcinoma.

Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.

Curative Resection for Metastatic Solid Pseudopapillary Neoplasm of Pancreas-a Case Series.

Solid pseudopapillary neoplasm (SPN) is an unusual tumor of the pancreas. Unlike ductal adenocarcinoma, SPN is commoner in young women and is indolent with better prognosis. Fifteen percent of patients, however, develop metastases, often synchronous and involving the liver or peritoneum. Owing to the paucity of cases, management of the metastatic disease is not clearly defined. Retrospective review of case notes of patients treated between 2006 and 2019. There were 53 patients with SPN of which 4 had hepatic metastases-3 synchronous and 1 metachronous. Two patients underwent simultaneous distal pancreatectomy and splenectomy with liver resection (right posterior sectionectomy and metastasectomy). One required right hepatectomy with metastasectomy for metachronous liver metastases. The other underwent a staged operation-remnant tumor excision with metastasectomy followed by right hepatectomy after portal vein embolization. All four patients are recurrence free on median follow-up of 38.5 months. In view of the excellent prognosis, we recommend radical resection of both the primary lesion and metastases for SPN.

Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.

INTRODUCTION: Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. METHOD: Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). RESULTS: Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. CONCLUSION: The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

Surgical management of sternal tumours-a decade of experience from a tertiary care centre in India.

Tumours of the sternum can be either primary or secondary with malignancy being the most common etiology. Wide local excision of these tumours results in a midline defect which pose a unique challenge for reconstruction. As limited data on the management of these tumours exists in the literature, we hereby report 14 consecutive patients who were treated at our institute between January 2009 to December 2020. Most of them were malignant with majority of them, 11 (78%) patients, with manubrial involvement requiring partial sternectomy. Overall, the average defect size was 75 cm2. Reconstruction of the chest wall defect was done using a semi-rigid fixation: mesh and suture stabilization in 3 (21%) or suture stabilization in 7 (50%) and without mesh or suture stabilization in 3 (21%) patients. Rigid fixation with polymethyl methacrylate (PMMA) was done for one patient (7%). Pectoralis major advancement flap was most commonly used for soft tissue reconstruction with flap necrosis noted in one patient (7%). There was no peri-operative mortality and one patient required prolonged post-operative ventilation. On a median follow-up of 37.5 months, one patient (7%) had a recurrence. Sternal defects after surgical resection reconstructed with semi-rigid fixation and suture stabilization render acceptable post-operative outcomes.

Focused panel sequencing points to genetic predisposition in non-cirrhotic intrahepatic portal hypertension patients in India.

OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. RESULT: Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. CONCLUSION: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

Rib malignancies masquerading as benign mediastinal tumours.

Mediastinal tumours are commonly encountered in general thoracic surgery practice. Benign tumours like thymoma and teratoma often need direct surgical resection if resectable. Pre-operative biopsy is not recommended. We report 2 cases which were radiologically diagnosed as thymoma and teratoma turned out to be Ewing sarcoma and chondrosarcoma respectively after surgical excision. This has challenged the notion whether biopsy is really not needed. More elaborate studies are needed to find out tumour characteristics which would warrant a biopsy even if they are resectable. In our cases, pre-operative biopsy would have changed the line of management in both patients. This has led to a change in institutional protocol that now, we do biopsy for any mediastinal tumour more than 8 cm and abutting the chest wall.

Pulmonary sclerosing pneumocytoma-a case series.

Pulmonary sclerosing pneumocytoma (PSP) is a rare and interesting pulmonary tumour that presents a diagnostic challenge to the surgeon due to its bland symptomatology, indolent course, non-specific radiological features and ambiguous histopathological findings, which could lead to errors in management and prognostication. Herein, we present a series of 4 patients with PSP who were managed in our institution over a period of 8 years and briefly discuss relevant literature.

Pulmonary mucormycosis-a case series.

Pulmonary mucormycosis (PM) is a rare disease. Literature about the surgical management of PM in India is sparse. Recently, there has been a surge in the number of cases of mucormycosis in association with the coronavirus disease 2019 (COVID-19) pandemic, igniting the interest in PM. Hence, we endeavoured to analyse our surgical experience in treating PM prior to the pandemic, in a tertiary care centre, to provide insight into this disease. Data of 10 adult patients with isolated PM, who underwent surgery between the years 2009 and 2020, and maintained in our departmental database, were retrieved and analysed.

Giant cystic pulmonary hamartoma-images.

Hamartoma is the commonest benign tumor of the lung. They usually present as an asymptomatic solitary solid nodule of varying size, located peripherally in the lung parenchyma and picked up incidentally in a chest X-ray. Rarely, they may be intra-bronchial in location. A giant cystic variant of hamartoma is very rare, with only a few cases reported in literature so far. It may be misdiagnosed as any other cystic disease of the lung and thus get mismanaged. We herewith present the images of a patient with a giant cystic pulmonary hamartoma who presented with respiratory distress.

Elucidating the anatomy of a rare communicating bronchopulmonary foregut malformation (CBPFM) in a preschool child.

Communicating bronchopulmonary foregut malformations (CBPFMs) are complex and rare anomalies. Their characteristic feature is an anomalous communication between the respiratory system (trachea, lung or bronchus) on one side and the gastrointestinal tract (oesophagus or stomach) on the other. Though acquired CBPFMs are known, the large majority of them are congenital and single. CBPFMs often go undetected even at surgery and require more than one operation before they are successfully addressed. This is because the symptomatology of CBPFM resembles the more common oesophageal atresia (OA) with tracheoesophageal fistula, wherein it may coexist. We report a patient with OA who had a rare form of CBPFM where the upper lobe of the right lung communicated with the upper oesophagus. This account highlights a novel method of working out the uncertain anatomy, in such cases. There may be associated anomalies of the lung parenchyma and vasculature usually involving the pulmonary arterial supply to the affected lung. Clinical, radiological, endoscopic and pathological characterisation permit precise diagnosis in most instances, with an occasional case that defies definition.

Case of functioning thoracic paraganglioma.

Functioning thoracic paraganglioma (PGL) is rare in clinical practice. We present a 33-year-old man with this pathology, who came with right-sided chest pain and was found to have a right-sided paravertebral mass. Fine needle aspiration cytology revealed a PGL. Urine normetanephrine was elevated and meta- iodobenzylguanidine scan showed increased tracer uptake in the right hemithorax, suggestive of a functioning neuroendocrine tumour. The patient was subjected to right PGL excision by video-assisted thoracoscopic surgery, after adequate preoperative preparations. The perioperative period was uneventful, except for a transient rise in blood pressure during the surgery. His blood pressure continued to be normal in the postoperative period. In any patient with a paravertebral mass, the possibility of PGL should be kept in mind even if the patient is normotensive. Making a preoperative diagnosis is important, because excision of functioning PGL without adequate preoperative preparation may be detrimental.

Role of Cross-sectional Imaging (CT/MRI) in Characterization and Distinguishing Benign from Malignant/Potentially Malignant Cystic Lesions of Pancreas.

OBJECTIVES: The aim of the study was to evaluate the accuracy of computed tomography/magnetic resonance imaging (CT/MRI) in characterizing cystic lesions of the pancreas and in differentiating between benign and malignant/potentially malignant lesions. MATERIAL AND METHODS: A retrospective study was performed on patients with pancreatic cystic lesions who underwent pre-operative imaging and surgery between October 2004 and April 2017 at a tertiary care teaching hospital. The images were reviewed for specific characteristics and diagnoses recorded independently by two radiologists who were blinded to the histopathological examination (HPE) report. Radiological diagnostic accuracy was assessed with HPE as reference standard. RESULTS: A total of 80 patients fulfilled the inclusion criteria (M: F = 27:53). The final HPE diagnoses were solid pseudopapillary neoplasm (32.5%), walled off necrosis/pseudocyst (27.5%), mucinous cystadenoma (15%), serous cystadenoma (11.25%), intraductal papillary mucinous neoplasm (8.75%), mucinous cystadenocarcinoma (2.5%), simple epithelial cyst (1.25%), and unspecified benign cystic lesion (1.25%). Observer1 correctly identified the diagnosis in 73.75% of cases while observer 2 did so in 72.5%. Sensitivity for distinguishing benign versus malignant/potentially malignant lesions was 85.1% for observer 1 and 80.9% for observer 2. On multivariate logistic regression analysis: Solid cystic morphology, presence of mural nodule, and female gender were associated with premalignant/malignant lesions. CONCLUSION: Cross-sectional imaging is a valuable tool for characterization of pancreatic cystic lesions within its limitations.

Organising pneumonia in Rhupus syndrome.

Interstitial lung disease (ILD) is seen in 17% of patients with Rhupus syndrome. Organising pneumonia (OP), a subtype of connective tissue disease-associated ILD, is rare but associated with good outcomes. Here, we present a patient with Rhupus who developed OP.

Intracholecystic papillary-tubular neoplasms of the gallbladder - A clinicopathological study of 36 cases.

Intracholecystic papillary-tubular neoplasms (ICPNs) account for <0.5% of all cholecystectomies. There is a lack of significant published data from the Indian subcontinent on ICPN to the best of our knowledge. The objective of the current study was to describe the clinicopathological features of ICPN of gallbladder from the departmental archives during a 5.5-year period. We also aimed to classify them into various histological subtypes and to correlate the clinicopathological parameters of ICPN with invasive adenocarcinoma. This study included 36 cases diagnosed over a period of 5.5 years (2013-2018). Clinical, radiological and histopathological data were analyzed in detail. The incidence of ICPN was 0.8%. The mean age of patients was 45.7 years with a female to male ratio of 1.3:1. Biliary phenotype was associated with invasion (p ≤0.001). Papillary pattern was present in 15 cases (41.6%) and was associated with invasion (p ≤0.001). High grade dysplasia was seen in 34 cases (94.4%), of which invasion was seen in 18 cases (50%). One case in our study also had synchronous common bile duct carcinoma. Majority (92%) of the patients were alive and well at the end of available follow-up (mean of 7 months and 25 days). ICPNs are mass forming neoplasms of the gallbladder with a slight female predominance. Biliary phenotype has an aggressive course, often associated with an invasive adenocarcinoma component. Papillary configuration of the lesion is significantly associated with an invasive component. Diligent follow-up of these lesions is warranted as they can be associated with other malignancies of the biliary system.

Is there a role for second transurethral resection in pTa high-grade urothelial bladder cancer?

INTRODUCTION: Evidence for second transurethral resection of bladder tumour (TURBT) for pTa high-grade lesions is limited. This study aims to examine the role of a second TURBT in the pTa high-grade group and to generate recurrence and progression data for this group. MATERIAL AND METHODS: We retrospectively studied the clinical profiles and outcomes of all patients diagnosed with high-grade pTa lesions at first TURBT, between the years 2006-2015. Firstly, in patients who underwent a complete first TURBT, we calculated the proportion of patients with positive findings on second TURBT. Secondly, we assessed whether those who underwent a second TURBT had a longer recurrence-free survival compared to those who underwent a single TURBT. RESULTS: One hundred and twelve patients had a pTa high-grade urothelial bladder tumor (WHO 2004 classification) at first TURBT, out of whom 43 (38.3%) had a second TURBT. Indications for second TURBT were high-grade lesions (n = 36), absence of detrusor muscle (n = 2), and incomplete resection (n = 5). Out of the 36 patients who had a complete first TURBT and underwent a second look TURBT, 7 patients had positive findings (3 carcinoma in situ, 2 pTa low-grade lesions and 2 pTa high-grade lesions) and there was no upstaging. Of the 5 patients with an incomplete first TURBT, one upstaged to pT1 on second TURBT. Of the 81 patients who followed up with us, 25.9% had a recurrence and 8.6% progressed. The estimated median recurrence free survival was 60 months (95% CI 29.2-90.7) for the whole group and 76 months vs. 45 months for the second and single TURBT group respectively - a difference that was clinically, though not statistically, significant. Multiple (≥2) tumours had a lower recurrence free survival (HR of 4.60, CI 1.67-12.63, p = 0.003). CONCLUSIONS: Of the patients with pTa high-grade tumours who had a second TURBT after a complete first TURBT, 19.4% had a positive finding. Multiple tumours are four times as likely to recur as solitary tumours. The role of a second TURBT in this group needs to be studied in larger patient cohorts before a recommendation regarding its lack of clinical utility can be made conclusively.

Cutaneous botryomycosis of the foot: A case report and review of literature.

Botryomycosis is a chronic bacterial infection that manifests clinically as tumours or plaques that are often ulcerated and have discharging sinuses draining small white-coloured granules. Therefore, they closely mimic mycetoma or other fungal infections. It is most commonly caused by Staphylococcus aureus. It can present as cutaneous or visceral disease. The cutaneous form can invade deep tissue leading to extensive destruction and disfigurement. A 31-year-old female presented with progressive swelling of her right foot over a period of 8 years. She had a disfigured right foot with multiple sinuses discharging pus. X-ray and magnetic resonance imaging of the foot showed invasion and destruction of the deep layers of the foot including the bone. Deep biopsy from the foot showed an abscess cavity with Gram-positive cocci within and bacterial culture grew S. aureus establishing the diagnosis of botryomycosis. Botryomycosis is a rare presentation of a common pathogen and needs to be considered while evaluating a chronic invasive subcutaneous infection.

Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India.

AIM OF THE STUDY: The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). METHODS: Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity. RESULTS: Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child's class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5 years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood. CONCLUSIONS: Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.