Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/ inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/ inoperable PPGL. Methods: This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (Plasma free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy. Results: A total of 15 patients PCC (4), sPGL (4), HNPGL (5), PCC+sPGL (1), HNPGL+sPGL (1) were included. The median duration of follow up was 27 (range: 11-62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53 %), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis presence of PGL (p= 0.044) and baseline SUVmax >21 (p < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and haematotoxicity. Conclusion: 177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.

Background and context: Glucagon-like peptide-1 receptor (GLP-1 R) based imaging has shown higher sensitivity for insulinoma localization as compared to other anatomic/functional imaging. Methodology:We reviewed the published English literature for GLP-1 R targeted imaging in insulinoma in PubMed until August 2020 in accordance with PRISMA guidelines using the MeSH terms "((Exendin-4 PET/CT) OR (Exendin-4 SPECT/CT) OR (GLP-1 R imaging)) AND (Insulinoma)". An individual patient data-metanalysis (IPD-MA) was performed, and performance parameters were calculated for the histopathological diagnosis of insulinoma.Main outcome measures: True-positive (TP), false-positive (FP), false-negative (FN), true-negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for insulinoma localization.Results: A total of 179 cases (316 lesions) from 16 publications were included for IPD-MA. For insulinoma localization, exendin-4-PET/CT (Sn & PPV: 94%) performed better than exendin-4-SPECT/CT (Sn: 63%, PPV: 94%). The Sn was lower in malignant insulinoma cases whereas the Sp was higher in cases with MEN-1 syndrome. With exendin-4-based imaging, FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in pancreatic tail lesions and malignancy were seen in a few patients. TN results suggested the correct diagnosis of other endogenous hyperinsulinemic hypoglycaemia (EHH) subtypes. Conclusion:For insulinoma localization, exendin-4 PET/CT should be preferred over exendin-4 SPECT/CT because of higher sensitivity and specificity. FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in tail lesions, and malignant insulinomas are limitations. Higher specificity for insulinoma localization is particularly useful in patients with MEN-1 syndrome.

Context: Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. Objective: To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. Design: Retrospective cross-sectional study. Patients: We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n = 11), Munchausen syndrome (MS) (n = 2) and inconclusive (n = 1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. Main Outcome Measures: True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. Results: In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. Conclusion: 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.

U‐500 insulin is five times the concentration of conventional U‐100 insulin, which is routinely used in the United Kingdom. Its use has been reported in severely resistant patients with type 2 diabetes requiring large insulin doses, with its use improving glycaemic control. There are no clear guidelines or indications on its use. This article discusses the practical aspects on the use of U‐500 insulin. Copyright © 2006 John Wiley & Sons, Ltd.

Background Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aimed to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin GITS (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP&lt;60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings The median (IQR) episodes (2 [1-3] vs. 0 [0-1], p 0·002) and duration of hypertension (19 [14-42] min vs. 0 [0-3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68–32·14%, p 0·002) were significantly higher in the prazosin GITS arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Interpretation Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.

BACKGROUNDOesophageal varices (EV) development is among the major complications of liver cirrhosis. Therefore, the current guidelines recommend screening of all liver cirrhosis patients for EV by endoscopy, but repeated endoscopic examinations are unpleasant for the patients, are not cost-effective and pose additional burden to endoscopic units. Therefore, non-invasive predictors of EV have been studied.The aim is to comparatively evaluate platelet count/spleen diameter (PC/SD) ratio, right liver lobe diameter (RLLD)/albumin ratio & left liver lobe diameter (LLLD)/albumin ratio as the non-invasive predictors of EV & their grading in patients with liver cirrhosis. MATERIALS AND METHODSThis study included 100 patients of liver cirrhosis which were subjected to laboratory investigations including platelet count & serum albumin concentration, abdominal ultrasound including measurement of RLLD, LLLD & spleen diameter and upper gastrointestinal endoscopy. PC/SD ratio, RLLD/albumin ratio & LLLD/albumin ratio were then calculated & comparatively evaluated statistically for their correlation with the presence & grading of EV. RESULTSPC/SD ratio, RLLD/albumin ratio and LLLD/albumin ratio had highly significant correlations with the presence and grading of EV (p<0.001 for each). The sensitivity, specificity and accuracy of PC/SD ratio in prediction of EV was 90.2%, 88.9% and 90% respectively at the best cut-off value of 1167.25 as calculated by applying receiver operating characteristic (ROC) curve. [AUC (Area under curve) =0.965]. The sensitivity, specificity and accuracy of RLLD/albumin ratio in prediction of EV was 74.4%, 94.4% and 78% respectively at the best cut-off value of 4.272 (AUC=0.835). The sensitivity, specificity and accuracy of LLLD/albumin ratio in prediction of EV was 89%, 83.3% and 88% respectively at the best cut-off value of 1.939 (AUC=0.931). PC/SD ratio, having the highest sensitivity, accuracy & area under ROC curve, was the best predictor of EV, followed by the LLLD/albumin ratio, which was further followed by RLLD/albumin ratio. CONCLUSIONPC/SD ratio, RLLD/albumin ratio & LLLD/albumin ratio are cost-effective noninvasive parameters that can provide accurate information pertinent to predict the presence & grading of EV in liver cirrhosis patients & amongst them PC/SD ratio is the b est predictor of EV, followed by LLLD/albumin ratio, which is further followed by RLLD/albumin ratio. KEYWORDSLeft Liver Lobe Diameter/Albumin Ratio, Platelet Count, Right Liver Lobe Diameter/Albumin Ratio, Spleen Diameter, Upper Gastrointestinal Endoscopy. HOW TO CITE THIS ARTICLE: Charan S, Garg R, Chander R, et al. A comparative evaluation of liver lobe size/albumin ratio and platelet count/spleen diameter ratio as non-invasive predictors of oesophageal varices in patients with liver cirrhosis.

A 38-year-old female presented with recurrent episodes of hypoglycemia for 5 years. On 72-h fast test, critical sample biochemistry was suggestive of endogenous hyperinsulinemic hypoglycemia. Both constrast-enhanced computed tomography and 68 Ga-DOTATATE positron emission tomography/computerized tomography (PET/CT) revealed no pancreatic lesion but showed a jejunal lesion suggestive of neuroendocrine tumor (NET) but not confirmatory of insulinoma. 68 Ga-Exendin-4 PET/CT showed intense uptake in the proximal jejunum, and this being a specific scan for insulinoma, confirmed it as an ectopic insulinoma. The patient attained normoglycemia after excision of this NET confirming it to be a case of ectopic insulinoma located in the jejunum. Although most insulinomas are located in the pancreas, rarely ectopic cases have been described in the spleen, perisplenic tissue, duodenohepatic ligament, adjacent to the ligament of Treitz, duodenum, and the jejunum. Functional scanning with 68 Ga-Exendin-4 PET/CT scan aids the localization of ectopic insulinoma.

Objective: Literature regarding utility of 68 Ga-DOTATATE PET/CT in insulinoma localization across various subgroups [benign/malignant/multiple endocrine neoplasia-1 (MEN-1) syndrome associated] remains scarce. In this study, the performance of 68 Ga-DOTATATE PET/CT was compared with contrast-enhanced computed tomography (CECT) and 68 Ga-NODAGA-Exendin-4 PET/CT (whenever available) in an endogenous hyperinsulinemic hypoglycemia (EHH) cohort. Design: Retrospective audit. Patients: EHH patients [N = 36, lesions (n) = 49, final diagnosis: benign sporadic insulinoma (BSI) (N = 20), malignant insulinoma (N = 4, n = 14), MEN-1 syndrome associated insulinoma (N = 9, n = 15), Munchausen syndrome (N = 2) and drug-induced hypoglycemia (N = 1)] having both preoperative imaging modalities (CECT and 68 Ga-DOTATATE PET/CT). Measurements: Per-lesion sensitivity (Sn) and positive predictive value (PPV) for histopathological diagnosis of insulinoma.Results: Sn and PPV of 68 Ga-DOTATATE PET/CT were 67.3% and 89.2%; 55% and 100%; 85.7% and 100%; and 66.7% and 77% for overall EHH, BSI, malignant, and MEN-1 syndrome associated insulinoma cohorts respectively. Despite having comparatively lower sensitivity in BSI cohort, 68 Ga-DOTATATE PET/CT localized a pancreatic tail lesion missed by other modalities. 68 Ga-DOTATATE PET/CT had comparatively higher sensitivity in malignant insulinoma than BSI cohort. 68 Ga-DOTATATE PET/CT also paved the way for successful response to 177 Lu-based peptide receptor radionuclide therapy (PRRT). In MEN-1 cases, lower PPV as compared with BSI was due to uptake in non-insulinoma pancreatic neuroendocrine tumours (Pan-NET).