Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma.

BACKGROUND: Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA. DESIGN: Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity. RESULTS: This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (p = 0.043). CONCLUSIONS: This transcriptomic classification could improve precision immunotherapy for GEA.

Caustic Ingestion: A Risk-Based Algorithm.

INTRODUCTION: Caustic ingestion management could be improved with a diagnostic approach based on risk factors. This study aimed to develop an algorithm derived from predictive factors of a poor clinical course, to evaluate its diagnostic accuracy and resource consumption, and to compare it with 2 other approaches, a radiological one based on computed tomography and a classical one based on symptoms and endoscopy. METHODS: All patients older than 15 years presenting with caustic ingestion in our tertiary care hospital between 1995 and 2021 were prospectively included. Adverse outcome was defined as intensive care unit admission, emergency surgery, or death. Ingestion characteristics, symptoms, and laboratory and endoscopic findings were analyzed to determine the most relevant risk factors. Diagnostic accuracy and the number of examinations required were estimated and compared with the other 2 algorithms applied to our series. RESULTS: The sample included 532 cases of caustic ingestion, 13.2% (95% confidence interval [CI]: 10.3-16.0) of which had adverse outcomes. Volume and type of caustic substance; presence of symptoms and pharyngolaryngeal involvement; and neutrophilia, acidosis, and endoscopic injury were combined to develop an algorithm that would provide the highest diagnostic odds ratio (167.2; 95% CI: 71.9-388.7). Following this approach, half of the patients (50.6%; 95% CI: 46.2-55.1) would not require any examination and, overall, the need for endoscopy (20.0%; 95% CI: 16.4-23.5) and computed tomography (16.3%; 95% CI: 13.0-19.5) would be lower than that for the other 2 algorithms. DISCUSSION: A risk-based algorithm could improve caustic ingestion management by maintaining high diagnostic accuracy while reducing diagnostic test requirements.

Sigmoid volvulus: outcomes of treatment and predictors of morbidity and mortality.

PURPOSE: To analyze the treatment outcomes for sigmoid volvulus (SV) and identify risk factors of complications and mortality. METHODS: Observational study of all consecutive adult patients diagnosed with SV who were admitted from January 2000 to December 2020 in a tertiary university institution for conservative management, urgent or elective surgery. Primary outcomes were 30-day postoperative morbidity, mortality and 2-year overall survival (OS), including analysis of risk factors for postoperative morbidity or mortality and prognostic factors for 2-year OS. RESULTS: A total of 92 patients were included. Conservative management was performed in 43 cases (46.7%), 27 patients (29.4%) underwent emergent surgery and 22 (23.9%) were scheduled for elective surgery. Successful decompression was achieved in 87.8% of cases, but the recurrence rate was 47.2%. Mortality rates following episodes were higher for conservative treatment than for urgent or elective surgery (37.2%, 22.2%, 9.1%, respectively; p = 0.044). ASA score > III was an independent risk factor for complications (OR = 5.570, 95% CI = 1.740-17.829, p < 0.001) and mortality (OR = 6.139, 95% CI = 2.629-14.335, p < 0.001) in the 30 days after admission. Patients who underwent elective surgery showed higher 2-year OS than those with conservative treatment (p = 0.011). Elective surgery (HR = 2.604, 95% CI = 1.185-5.714, p = 0.017) and ASA score > III (HR = 0.351, 95% CI = 0.192-0.641, p = 0.001) were independent prognostic factors for 2-year OS. CONCLUSION: Successful endoscopic decompression can be achieved in most SV patients, but with the drawbacks of high recurrence, morbidity and mortality rates. Concurrent severe comorbidities and conservative treatment were independent prognostic factors for morbidity and survival in SV.

Surgical treatment of an intraductal papillary mucinous neoplasm of the biliary tract diagnosed by SpyGlass®.

We present the case of a 76-year-old male with a history of acute cholecystitis who underwent a scheduled laparoscopic cholecystectomy. Chronic cholecystitis with a thickened cystic duct was observed intraoperatively. The anatomic pathology report found high-grade dysplasia that affected the distal edge of the cystic duct. In view of these findings, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with SpyGlass® and an excrescent lesion suggestive of malignancy adjacent to the cystic-common bile duct junction was observed. A resection of the extrahepatic bile duct was performed with lymphadenectomy of the hepatic hilum and hepaticojejunostomy in a subsequent procedure. The definitive pathology report confirmed pancreaticobiliary intraductal papillary mucinous neoplasia with high-grade dysplasia and free margins.

Caustic ingestion: development and validation of a prognostic score.

BACKGROUND: Caustic ingestion is a potentially severe condition and early identification of poor outcome is essential to improve management; however, prediction based on endoscopy alone can overestimate severity. This study aimed to develop and validate a prognostic score. METHODS: A prospective cohort study was designed to include all consecutive patients aged > 15 years who presented with caustic ingestion between 1995 and 2017. Adverse outcome was defined by intensive care unit admission, urgent surgery, or death. The predictive value of clinical, analytical, and endoscopic variables was assessed in the first cohort (derivation cohort) and a prognostic score based on the resulting risk factors was developed by logistic regression. Internal validation (bootstrapping) was performed and then external validation was checked in an independent sample of patients (validation cohort). RESULTS: 469 cases of caustic ingestion were included, 265 in the derivation cohort and 204 in the validation cohort. Ingestion of acidic substances (odds ratio [OR] 3.13, 95 % confidence interval [CI] 2.33 - 4.21), neutrophil count (OR 1.05, 95 %CI 1.04 - 1.06), metabolic acidosis (bicarbonate value, OR 0.82, 95 %CI 0.78 - 0.85), and endoscopic injury (OR 3.81, 95 %CI 3.35 - 4.34) were independent risk factors for poor outcome. The prognostic score based on these variables provided better accuracy than endoscopy alone (P = 0.04), with high sensitivity, specificity, positive and negative predictive values (93.3 %, 92.7 %, 72.7 %, 98.5 %, respectively), and area under the curve (0.976, 95 %CI 0.973 - 0.979; P < 0.001). CONCLUSIONS: This score allowed a reliable prognosis of caustic ingestion and was more accurate than endoscopy-based evaluation.

Disconnected pancreatic duct syndrome: complete pancreas transection secondary to acute pancreatitis.

Disconnected pancreatic duct syndrome is a serious complication of acute pancreatitis which is defined by a complete discontinuity of the pancreatic duct, such that a viable side of the pancreas remains isolated from the gastrointestinal tract. This pancreatic disruption is infrequently observed in the clinical practice and its diagnostic and therapeutic management are controversial. We present an extreme case of disconnected pancreatic duct syndrome with complete duct disruption and pancreatic transection following acute pancreatitis, as well as the diagnostic and therapeutic processes carried out.

Methotrexate induced sprue-like syndrome.

A 52 year-old male patient diagnosed of ankylosing spondylitis presented with an iron deficiency anemia after a ten-month treatment of methotrexate. He did not respond to treatment with oral iron not a proton pump inhibitor and an upper endoscopy was performed. The histological study of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administering intramuscular iron and undertaking a gluten-free diet, the histological and analytical alterations progressively resolved.