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The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown. We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles. In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of and or (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively. Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).

Introduction Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited in the SSTR-based imaging such as 111In octreotide scintigraphy and 68Ga DOTATATE positron emission tomography (PET)/CT. These modalities are currently considered standard for initial evaluation of suspected NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head - a confounding common site of NET involvement. Case report: A 78 year-old woman presented to clinic with a year-long history of diarrhea. Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL. CT showed a mildly enhancing 2.5x1.8x2.8 cm area in the pancreatic uncinate process which corresponded to moderate focal uptake with 68Ga DOTATATE PET/CT. A presumptive diagnosis of NET was made, and the patient was scheduled to undergo Whipple’s surgery. She sought a second opinion at our institution. A subsequent MRI showed no lesion in the uncinate process and the patient’s surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Conclusion Conspicuous physiological uptake has been reported in the pancreatic head on 16-70% of 68Ga DOTATATE or 68Ga DOTANOC PET/CT scans, and 26% of the 111In octreotide scintigraphy scans.1 Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by means such as MRI or EUS. The patient described above also had mild contrast enhancement on CT, but an MRI didn’t show any corresponding lesion. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care. 1. Brabander T, et al. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism. Clin Nucl Med 2017;42:15-9. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Introduction MEN1 is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Carcinoids occur in 5-15% patients, majority of which are of foregut origin (thymus, bronchus, stomach and duodenum). Only 1 case of ovarian carcinoid has been reported in association with MEN1, and was not confirmed with genetic testing. Case report A 33-year-old female with a macroprolactinoma and primary hyperparathyroidism was referred to us with a presumptive diagnosis of MEN1. Genetic testing showed a heterozygous germline mutation in the MEN1 gene, c.219_220delCG (frameshift leading to premature protein truncation). She had no family history consistent with MEN1. EGD showed two submucosal nodules in the duodenum with confirmed histology of gastrinomas. CT demonstrated 8.7 x 7.7 cm right adnexal mass containing foci of soft tissue density and calcification. Laparoscopic resection was attempted but the mass was too large to be delivered en-bloc. Operative approach was changed to a minilaparotomy and the mass was delivered in a piecemeal fashion. Pathology demonstrated a benign dermoid cyst with neuroendocrine tumor consistent with carcinoid extending into peri-ovarian tissues. 4 years later, she presented with a lower abdominal palpable mass. CT showed an irregular, avidly enhancing 11.7 x 8.7 cm pelvic mass, extending through the anterior abdominal wall into the subcutaneous fat with satellite lesions within the anterior subcutaneous abdomen. The CT abnormalities corresponded to abnormally elevated In-111 pentetreotide uptake. Biopsy of one of the subcutaneous lesions showed metastatic neuroendocrine neoplasm with Ki67 index of 2%. Targeted genetic analysis for the patient’s MEN1 mutation using DNA samples isolated from the primary adnexal mass as well as the recurrent abdominal wall tumor demonstrated predominantly mutant sequence in both specimens, confirming LOH at the MEN1 gene locus. 5 months later, the patient presented with obstructive uropathy from nodal metastases. She underwent debulking surgery via exploratory laparotomy, panniculectomy, resection of metastatic abdominal wall tumors and abdominal wall reconstruction. Post operatively, FDG-PET scan showed few scattered disease foci. She was commenced on monthly octreotide injections. Conclusions This case represents to our knowledge, the first genetically confirmed case of ovarian carcinoid arising by a MEN1 mechanism. Ovarian carcinoid should be considered as a differential in MEN1 patients with adnexal mass. Extreme caution should be exercised during surgical resection, as failure to remove an ovarian carcinoid en masse can result in peritoneal seeding and recurrence. For patients with advanced disease, systemic therapy options include somatostatin receptor analogs, peptide receptor radioligand therapy, and novel agents targeting mTOR and VEGF. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

The co-occurrence of Guillain–Barre syndrome (GBS) and tuberculosis is rare. Even in countries like India, where tuberculosis is common, there is only one case report of co-occurrence of GBS with tuberculosis. We report a case of GBS in association with sputum-positive pulmonary tuberculosis. The earliest treatment with intravenous immunoglobulin in acute motor axonal neuropathy variant of GBS would show good early recovery despite associated pulmonary tuberculosis.

Background and aims Acute upper gastrointestinal (UGI) bleeding is one of the serious and potentially life-threatening medical emergencies, causing significant mortality and morbidity. This study aimed to evaluate the clinico-endoscopic profile and outcome among patients aged <60 years who presented for UGI bleeding compared to those aged ≥60 years. Methods This prospective observational study was conducted among 194 patients who presented with symptoms or signs of UGI bleed. All patients were divided into two groups, group A (age <60 years), and group B (age ≥60 years). UGI endoscopy was performed using Olympus N19 Endoscope. Rockall scoring (RS) system and Glasgow Blatchford score (GBS) were used to predict the prognosis and re-bleeding. Results Of the total, group A included 150 (77.31%) patients and group B 44 (22.69%) patients. The most common presentation was hematemesis and melena in both groups, whilst isolated hematochezia was more common in group A (6.67%, vs. 2.27%, p>0.05). The main cause of bleeding was a variceal bleed in both groups, but it was significantly higher in group A patients (p<0.05). Elderly patients had a significantly higher number of peptic ulcer and malignancy-related bleed (p<0.05). Group A patients had a significantly higher proportion of patients with tachycardia (45.33%, vs. 27.27%, p<0.05), shock (43.33% vs. 13.63%, p<0.05), pallor (76.66% vs. 56.81%, p<0.05), and blood transfusion requirement (64% vs. 45.45%, p<0.05) as compared to group B. Thirty days re-bleeding and mortality rate were similar in both the groups. RS in both groups was 5.02±2.12 vs. 5.98±1.91, p>0.05. GBS was 11.65±4.61 vs. 10.68±4.65, p>0.05. Mortality was significantly higher in patients with RS ≥6 and GBS ≥10. Conclusion This study concluded variceal bleeding as a predominant cause of UGI bleed in both age groups, and it was significantly higher in younger. Interestingly, younger patients were more hemodynamically unstable, probably due to the presence of more severe anemia, shock, and hematochezia. The presence of multiple co-morbidities in both the group kept the 30 days mortality and re-bleed rates similar.

Weakly supervised object localization (WSOL) aims at predicting object locations in an image using only image-level category labels. Common challenges that image classification models encounter when localizing objects are, (a) they tend to look at the most discriminative features in an image that confines the localization map to a very small region, (b) the localization maps are class agnostic, and the models highlight objects of multiple classes in the same image and, (c) the localization performance is affected by background noise. To alleviate the above challenges we introduce the following simple changes through our proposed method ViTOL. We leverage the vision-based transformer for self-attention and introduce a patch-based attention dropout layer (p-ADL) to increase the coverage of the localization map and a gradient attention rollout mechanism to generate class-dependent attention maps. We conduct extensive quantitative, qualitative and ablation experiments on the ImageNet-1K and CUB datasets. We achieve state-of-the-art MaxBoxAcc-V2 localization scores of 70.47% and 73.17% on the two datasets respectively. Code is available on https://github.com/Saurav-31/ViTOL