Endoscopic Ultrasound for the Treatment of Gastric Variceal Bleeding in a Patient with Portal Cavernoma

"A 30-year-old lady was admitted with two weeks of fever and right upper quadrant pain. She had a background of non-malignant, non-cirrhotic portal vein thrombosis (PVT) with cavernoma formation. There was no detected underlying pro-thrombotic condition. She had established portal hypertension with esophageal varices. Her portal cavernoma was complicated by portal biliopathy and concurrent gallstone disease - with an endoscopic retrograde cholangio-pancreatography (ERCP) and stenting four weeks prior to admission. Drug history included carvedilol for primary prophylaxis of bleeding, anticoagulation had not been undertaken due to collateralisation. Admission computerised tomography (CT) revealed multiple small liver abscesses with a patent biliary stent and no progression of PVT and she was treated conservatively with intravenous antibiotics."--Case summary and discussionAlexander Boyd (1, 2, 3), Brinder S Mahon (2), Neil Rajoriya (2, 3) ; 1. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham. 2. University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way. 3. University of BirminghamIncludes bibliographical reference

Pancreatic insulinoma co-existing with gastric GIST in the absence of neurofibromatosis-1

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumours (GIST) frequently occur in patients with neurofibromatosis type 1 (NF-1). It has been reported that GIST may co-exist with pancreatic endocrine tumors but this has only been in association with NF-1.</p> <p>Case presentation</p> <p>A 76 year old woman presented with a 12 month history of hypoglycaemia symptoms. Abdominal CT scan demonstrated a 13 mm insulinoma localized in the tail of her pancreas. She was commenced on diazoxide and later underwent surgery for enucleation of insulinoma when a small (< 1 cm) incidental tumour was discovered on her stomach wall which was identified as GIST.</p> <p>Conclusion</p> <p>This is the first case report of a pancreatic insulinoma co-existing with a GIST in a patient without NF-1. In addition, we make the first report of rapidly growing cystic GIST recurrence following resection of a primary GIST tumour.</p

Technical and clinical outcomes following EUS-guided thrombin injection and coil implantation for parastomal varices

Background and aims Bleeding from parastomal varices causes significant morbidity and mortality. Treatment options are limited, particularly in high-risk patients with significant underlying liver disease and other comorbidities. The use of EUS-guided embolisation coils combined with thrombin injection in gastric varices has been shown to be safe and effective. Our institution has applied the same technique to the treatment of parastomal varices.Methods A retrospective review was performed of 37 procedures on 24 patients to assess efficacy and safety of EUS-guided injection of thrombin, with or without embolisation coils for treatment of bleeding parastomal varices. All patients had been discussed in a multidisciplinary team meeting, and correction of portal hypertension was deemed to be contraindicated. Rebleeding was defined as stomal bleeding that required hospital admission or transfusion.Results All patients had significant parastomal bleeding at the time of referral. 100% technical success rate was achieved. 70.8% of patients had no further significant bleeding in the follow-up period (median 26.2 months) following one procedure. 1-year rebleed-free survival was 80.8% following first procedure. 7 patients (29.1%) had repeat procedures. There was no significant difference in rebleed-free survival following repeat procedures. Higher age was associated with higher risk of rebleeding. No major procedure-related complications were identified.Conclusions EUS-guided thrombin injection, with or without embolisation coils, is a safe and effective technique for the treatment of bleeding parastomal varices, particularly for patients for whom correction of portal venous hypertension is contraindicated

Technical and clinical outcomes following EUS-guided thrombin injection and coil implantation for parastomal varices

Background and aims Bleeding from parastomal varices causes significant morbidity and mortality. Treatment options are limited, particularly in high-risk patients with significant underlying liver disease and other comorbidities. The use of EUS-guided embolisation coils combined with thrombin injection in gastric varices has been shown to be safe and effective. Our institution has applied the same technique to the treatment of parastomal varices.Methods A retrospective review was performed of 37 procedures on 24 patients to assess efficacy and safety of EUS-guided injection of thrombin, with or without embolisation coils for treatment of bleeding parastomal varices. All patients had been discussed in a multidisciplinary team meeting, and correction of portal hypertension was deemed to be contraindicated. Rebleeding was defined as stomal bleeding that required hospital admission or transfusion.Results All patients had significant parastomal bleeding at the time of referral. 100% technical success rate was achieved. 70.8% of patients had no further significant bleeding in the follow-up period (median 26.2 months) following one procedure. 1-year rebleed-free survival was 80.8% following first procedure. 7 patients (29.1%) had repeat procedures. There was no significant difference in rebleed-free survival following repeat procedures. Higher age was associated with higher risk of rebleeding. No major procedure-related complications were identified.Conclusions EUS-guided thrombin injection, with or without embolisation coils, is a safe and effective technique for the treatment of bleeding parastomal varices, particularly for patients for whom correction of portal venous hypertension is contraindicated

NK cells in pancreatic cancer demonstrate impaired cytotoxicity and a regulatory IL-10 phenotype.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common tumor subtypes and remains associated with very poor survival. T cell infiltration into tumor tissue is associated with improved clinical outcome but little is known regarding the potential role of NK cells in disease control. Here we analyze the phenotype and function of NK cells in the blood and tumor tissue from patients with PDAC. Peripheral NK cells are present in normal numbers but display a CD16CD57 phenotype with marked downregulation of NKG2D. Importantly, these cells demonstrate reduced cytotoxic activity and low levels of IFN-γ expression but instead produce high levels of intracellular IL-10, an immunoregulatory cytokine found at increased levels in the blood of PDAC patients. In contrast, NK cells are largely excluded from tumor tissue where they display strong downregulation of both CD16 and CD57, a phenotype that was recapitulated in primary NK cells following co-culture with PDAC organoids. Moreover, expression of activatory proteins, including DNAM-1 and NKP30, was markedly suppressed and the DNAM-1 ligand PVR was strongly expressed on tumor cells. As such, and peripheral NK cells display differential features in patients with PDAC and indicate local and systemic mechanisms by which the tumor can evade immune control. These findings offer a number of potential options for NK-based immunotherapy in the management of patients with PDAC

Role of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic and peripancreatic lesions: is onsite cytopathology necessary?

AbstractObjectivesThe reported median diagnostic yield from endoscopic ultrasound (EUS) fine-needle aspiration (FNA) cytology is 78% (range 39–93%). The aim of this study is to describe a single-centre experience in the diagnostic work-up of solid pancreatic and peripancreatic masses without the benefit of an onsite cytopathologist.MethodsIn a consecutive series of 429 EUS examinations performed over a 12-month period by a single operator, 108 were on non-cystic pancreatic or biliary lesions. Data were collected prospectively and the accuracy of FNA was assessed retrospectively using either surgery or repeat imaging as the benchmark in the presence or absence of malignancy.ResultsOf the 108 FNAs, 102 (94%) were diagnostic, four were falsely negative (FN) and two were atypical and considered equivocal. There were 78 pancreatic lesions, of which 65 were true positives (TP), 11 true negatives (TN) and two FN, giving an overall accuracy of 97% (76/78). Of nine periampullary lesions, two were TP, six were TN and one was FN, giving an overall accuracy of 89% (8/9). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of EUS-FNA for pancreatic and periampullary lesions combined were 96%, 100%, 100% [95% confidence interval (CI) 95–100%], 85% (95% CI 62–97%) and 97%, respectively. There were 21 bile duct lesions, of which 10 were TP, eight TN, two atypical and one FN, giving an overall accuracy of 86% (18/21). The sensitivity, specificity, PPV, NPV and accuracy of EUS-FNA for biliary lesions were 91%, 100%, 100% (95% CI 69–100%), 91% (95% CI 59–100%) and 95%, respectively.ConclusionsThe diagnostic accuracy of EUS-FNA for pancreatic lesions in our series was 97% and the PPV for the three subgroups of lesion type was 100%; these figures are comparable with the best rates reported in the literature, despite the absence of onsite cytopathology. These rates are potentially a direct result of high-volume practice, dedicated endosonography and cytopathology. These results show that it is possible to achieve high rates of accuracy in places where logistical issues make it impossible to maintain a cytopathologist in the endoscopy suite. In addition, our results contribute to the limited, collective global experience on the effectiveness of EUS-FNA in periampullary and biliary lesions

Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here, we combine spatial transcriptomics and scRNA-Seq datasets to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and link this to clinical outcome. Tumor-proximal fibroblasts comprise large populations of myofibroblasts, strongly expressed podoplanin, and were enriched for Wnt ligand signaling. In contrast, inflammatory CAFs were dominant within tumor-distal subsets and expressed complement components and the Wnt-inhibitor SFRP2. Poor clinical outcome was correlated with elevated HIF-1α and podoplanin expression whilst expression of inflammatory and complement genes was predictive of extended survival. These findings demonstrate the extreme transcriptional heterogeneity of CAFs and its determination by apposition to tumor. Selective targeting of tumor-proximal subsets, potentially combined with HIF-1α inhibition and immune stimulation, may offer a multi-modal therapeutic approach for this disease