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GI Surgery – Biliary Tract and Pancreas

RCT: Cabozantinib Improves Progression-Free Survival in Advanced Neuroendocrine Tumors

17 Sep, 2024 | 11:03h | UTC

Background: Advanced neuroendocrine tumors (NETs) present limited treatment options, with many patients experiencing disease progression despite existing therapies. Angiogenesis is pivotal in NET pathogenesis. Cabozantinib, an oral tyrosine kinase inhibitor targeting VEGF receptors, MET, AXL, and RET, has demonstrated clinical activity in phase 2 studies involving NETs. The efficacy of cabozantinib in patients with progressive, advanced extrapancreatic or pancreatic NETs after prior treatments remains uncertain.

Objective: To assess the efficacy and safety of cabozantinib compared with placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs.

Methods: A multicenter, double-blind, randomized, placebo-controlled phase 3 trial (CABINET) was conducted at 62 sites in the United States from October 2018 to August 2023. Eligible patients were adults aged ≥18 years with histologically confirmed, locally advanced or metastatic well- or moderately differentiated extrapancreatic or pancreatic NETs (WHO grades 1–3) and documented disease progression within 12 months prior to enrollment. Patients were randomized 2:1 to receive cabozantinib (60 mg orally once daily) or placebo. Randomization was stratified by concurrent somatostatin analogue use and primary tumor site. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review according to RECIST 1.1 criteria. Key secondary endpoints included objective response rate (ORR), overall survival (OS), and safety.

Results: A total of 203 patients with extrapancreatic NETs and 95 patients with pancreatic NETs were randomized.

  • Extrapancreatic NET Cohort:
    • Median PFS was 8.4 months with cabozantinib vs. 3.9 months with placebo (stratified hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.25–0.59; P<0.001).
    • Partial responses were observed in 5% of patients receiving cabozantinib vs. 0% with placebo.
  • Pancreatic NET Cohort:
    • Median PFS was 13.8 months with cabozantinib vs. 4.4 months with placebo (stratified HR, 0.23; 95% CI, 0.12–0.42; P<0.001).
    • Partial responses were observed in 19% of patients receiving cabozantinib vs. 0% with placebo.

Grade ≥3 treatment-related adverse events occurred in 62–65% of patients receiving cabozantinib and 23–27% receiving placebo. Common grade ≥3 adverse events included hypertension (21–22%), fatigue (11–13%), diarrhea (11%), and thromboembolic events (11%).

Conclusions: Cabozantinib significantly improved progression-free survival compared to placebo in patients with previously treated, progressive advanced extrapancreatic or pancreatic NETs. The safety profile was consistent with known adverse events associated with cabozantinib.

Implications for Practice:

  • New Treatment Option: Cabozantinib offers a new therapeutic avenue for patients with advanced NETs who have progressed after prior therapies.
  • Broad Applicability: The findings support the use of cabozantinib in both extrapancreatic and pancreatic NETs.
  • Adverse Event Management: Clinicians should closely monitor and manage treatment-related adverse events to optimize patient outcomes.

Study Strengths and Limitations: Strengths include a large sample size, randomized controlled design, and inclusion of patients who had progressed after standard therapies, enhancing the applicability of the findings to clinical practice. Limitations involve early trial termination based on interim analysis, which may overestimate the treatment effect, the use of placebo rather than an active comparator, and the high rate of dose modifications due to adverse events.

Future Research: Further studies should explore the optimal sequencing of cabozantinib with other therapies in NETs and investigate combination treatments. Long-term studies assessing overall survival benefits and quality of life are warranted.

Reference: Chan JA, Geyer S, Zemla T, et al. Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors. N Engl J Med. Published online September 16, 2024. doi:10.1056/NEJMoa2400702

 

Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol

18 Aug, 2024 | 19:23h | UTC

Study Design and Population: This systematic review and meta-analysis compared the safety and efficacy of nasogastric (NG) versus nasojejunal (NJ) feeding initiated within 48 hours of hospital admission in patients with moderate to severe acute pancreatitis. The analysis included four randomized controlled trials (RCTs) involving a total of 217 patients.

Main Findings: The review found no significant difference in mortality between NG and NJ feeding groups. However, NG feeding was associated with a higher incidence of diarrhea (RR 2.75, P = 0.02) and pain (RR 2.91, P = 0.002). The risk of infection was also higher in the NG group (6.67% vs. 3.33%, P = 0.027). No significant differences were observed in the need for surgical intervention, the requirement for parenteral nutrition, or the success rates of feeding procedures.

Implications for Practice: The findings suggest that while NG feeding does not increase mortality in acute pancreatitis, it is associated with higher rates of certain complications, particularly diarrhea and pain. Clinicians should consider these risks when choosing a feeding strategy for patients with acute pancreatitis, especially within the critical early 48-hour period post-admission.

Reference: Wang M, Shi H, Chen Q, Su B, Dong X, Shi H, Xu S. (2024). Comparative safety assessment of nasogastric versus nasojejunal feeding initiated within 48 hours post-admission versus unrestricted timing in moderate or severe acute pancreatitis: a systematic review and meta-analysis. BMC Gastroenterology, 24(207), 1-11. DOI: 10.1186/s12876-024-03290-z.

 

ACG Guideline: Management of Acute Pancreatitis

20 Mar, 2024 | 21:49h | UTC

This guideline, crafted by the American College of Gastroenterology, provides essential strategies for managing acute pancreatitis, offering a concise overview of diagnosis, treatment, and prevention recommendations for healthcare professionals. Here is a summary of the key information contained in the document:

 

  1. Introduction and Epidemiology: Acute pancreatitis (AP) is one of the most common gastrointestinal diseases leading to hospitalization in the United States, with about 300,000 admissions annually and a cost of over 2.5 billion dollars. The incidence of AP has been increasing annually, although the mortality rate has remained stable due to advancements in management.
  2. Etiology and Diagnosis: AP is typically caused by gallstones and alcohol consumption. Diagnosis is made based on the presence of two of the following three criteria: characteristic abdominal pain, serum amylase and/or lipase levels more than three times the upper limit of normal, and/or characteristic findings on abdominal imaging.
  3. Initial Management and Hydration: Initial management emphasizes the importance of moderate to aggressive intravenous hydration, preferably with lactated Ringer’s solution over normal saline, due to its potential benefit in reducing systemic inflammation and preventing complications.
  4. Nutrition: Patients with mild AP are encouraged to start early oral feeding within 24 to 48 hours as tolerated, preferring a low-fat solid diet over a progressive approach from liquids to solids.
  5. Management of Complications: The document addresses the management of complications such as pancreatic necrosis, suggesting the use of antibiotics only in cases of infected necrosis and highlighting a preference for minimally invasive methods of debridement and necrosectomy.
  6. Prevention of Recurrence and Role of ERCP: To prevent recurrences in biliary pancreatitis, cholecystectomy is recommended. In selected cases of acute biliary pancreatitis without cholangitis, medical therapy is preferred over early ERCP.
  7. Use of Antibiotics: The guidelines discourage the prophylactic use of antibiotics in cases of severe AP without evidence of infection, due to the lack of demonstrated benefit and potential risks.

 

Tenner, S. et al (2024). American College of Gastroenterology Guidelines: Management of Acute Pancreatitis. The American Journal of Gastroenterology, 119(3), 419-437. https://doi.org/10.14309/ajg.0000000000002645

Proposed algorithm for appropriate fluid management in acute pancreatitis

8 Aug, 2023 | 13:33h | UTC

Fluid treatment in acute pancreatitis: a careful balancing act – British Journal of Surgery

Related:

Update on the management of acute pancreatitis – Current Opinion in Critical Care

Intravenous fluid therapy in patients with severe acute pancreatitis admitted to the intensive care unit: a narrative review – Intensive Care Medicine

Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis – New England Journal of Medicine

Acute Pancreatitis: Diagnosis and Treatment – Drugs

Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis – Gut and Liver

Guidelines for the management of patients with severe acute pancreatitis, 2021 – Anaesthesia Critical Care & Pain Medicine

Evidence-Based Disposition of Acute Pancreatitis – emDocs

2019 WSES guidelines for the management of severe acute pancreatitis – World Journal of Emergency Surgery

American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis

Pancreatitis – National Institute for Health and Care Excellence

The optimal timing and intervention to reduce mortality for necrotizing pancreatitis: a systematic review and network meta-analysis – World Journal of Emergency Surgery

Long-term follow-up of a RCT | Endoscopic versus surgical step-up approach for infected necrotizing pancreatitis.

RCT: Immediate drainage did not improve outcomes compared to postponed intervention in patients with infected necrotizing pancreatitis.

An Endoscopic Transluminal Approach, Compared With Minimally Invasive Surgery, Reduces Complications and Costs for Patients With Necrotizing Pancreatitis – Gastroenterology

Research: Endoscopic or Surgical Step-up Approach for Infected Necrotising Pancreatitis

Evidence-Based Approach to the Surgical Management of Acute Pancreatitis – The Surgery Journal

 

RCT | Exploring the impact of total pancreatectomy with islet autotransplantation to reduce postoperative complications

8 Aug, 2023 | 13:25h | UTC

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial – Annals of Surgery

 

Determination of “borderline resectable” pancreatic cancer – A global assessment of 30 shades of grey

8 Aug, 2023 | 13:22h | UTC

Determination of “borderline resectable” pancreatic cancer – A global assessment of 30 shades of grey – HPB

 

Commentary on Twitter

 

Consensus Paper | Minimally invasive pancreatic surgery

8 Aug, 2023 | 13:20h | UTC

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS) – Annals of Surgery

 

Review | Contemporary artery-first approaches in pancreatoduodenectomy

27 Jun, 2023 | 13:43h | UTC

Contemporary artery-first approaches in pancreatoduodenectomy – British Journal of Surgery

 

Cohort Study | Dengue patients at high risk of cholecystitis and pancreatitis within 30 days

21 Jun, 2023 | 13:34h | UTC

Risks of Acute Cholecystitis, Acute Pancreatitis, and Acute Appendicitis in Patients with Dengue Fever: A Population-Based Cohort Study in Taiwan

 

Review | Serial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: what is the evidence?

21 Jun, 2023 | 13:27h | UTC

Serial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: What is the evidence? – Cleveland Clinic Journal of Medicine

 

Cohort Study | UK pancreatitis study reveals gallstones as most common cause

29 May, 2023 | 10:57h | UTC

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK – BMJ Open

 

Commentary on Twitter

 

Review | Hereditary colorectal, gastric, and pancreatic cancer

18 May, 2023 | 13:43h | UTC

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review – BJS Open

 

Commentary on Twitter

 

Fluorescence-guided surgery: comprehensive review

18 May, 2023 | 13:34h | UTC

Fluorescence-guided surgery: comprehensive review – BJS Open

 

Commentary on Twitter

 

Current perioperative care in pancreatoduodenectomy: a step-by-step surgical roadmap from first visit to discharge

16 May, 2023 | 14:52h | UTC

Current Perioperative Care in Pancreatoduodenectomy: A Step-by-Step Surgical Roadmap from First Visit to Discharge – Cancers

 

Commentary on Twitter

 

RCT | Interrupted vs. continuous suture technique for biliary-enteric anastomosis

16 May, 2023 | 14:22h | UTC

Interrupted versus continuous suture technique for biliary-enteric anastomosis: randomized clinical trial – BJS Open

 

Commentary on Twitter

 

Review | Predicting postoperative pancreatic fistula and pancreatitis after pancreatoduodenectomy or distal pancreatectomy

10 May, 2023 | 15:41h | UTC

Prediction of postoperative pancreatic fistula and pancreatitis after pancreatoduodenectomy or distal pancreatectomy: A review – Scandinavian Journal of Surgery

 

Commentary from the author on Twitter

 

EASL-ILCA Clinical practice guidelines on the management of intrahepatic cholangiocarcinoma

9 May, 2023 | 14:47h | UTC

EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma – Journal of Hepatology

 

Commentary on Twitter

 

Guideline | Perioperative management of patients undergoing endoscopic retrograde cholangiopancreatography

4 May, 2023 | 13:52h | UTC

Consensus guidelines for the perioperative management of patients undergoing endoscopic retrograde cholangiopancreatography – British Journal of Anaesthesia

 

Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis

3 May, 2023 | 15:22h | UTC

Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis – Gut

 

Review | Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma

28 Apr, 2023 | 13:03h | UTC

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma – CA: A Cancer Journal for Clinicians

 

SR | Etiology, diagnosis, and modern management of chronic pancreatitis

24 Apr, 2023 | 13:29h | UTC

Etiology, Diagnosis, and Modern Management of Chronic Pancreatitis: A Systematic Review – JAMA Surgery (free for a limited period)

 

RCT | Piperacillin-tazobactam better than cefoxitin in antimicrobial prophylaxis for open pancreatoduodenectomy

21 Apr, 2023 | 13:08h | UTC

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial – JAMA (free for a limited period)

Editorial: Informing a Rational Approach to Antimicrobial Prophylaxis in Open Pancreatoduodenectomy – JAMA (free for a limited period)

 

Commentary on Twitter

 

Review | Diagnostic, structured classification and therapeutic approach in cystic pancreatic lesions

12 Apr, 2023 | 12:58h | UTC

Diagnostic, Structured Classification and Therapeutic Approach in Cystic Pancreatic Lesions: Systematic Findings with Regard to the European Guidelines – Diagnostics

Related:

Diagnostic Approach to Incidentally Detected Pancreatic Cystic Lesions – Current Treatment Options in Gastroenterology

Cystic pancreatic lesions: MR imaging findings and management.

Recommendations for the management of incidental pancreatic findings in adults.

Pancreatic cystic neoplasms: a review of current recommendations for surveillance and management

Management of Pancreatic Cystic Lesions

Consensus Recommendations: Diagnosis and Surveillance of Incidental Pancreatic Cystic Lesions

Review: Pancreatic Cystic Lesions

Guidelines on pancreatic cystic neoplasms

 

SR | Risk factors for cholangitis after pancreatoduodenectomy

11 Apr, 2023 | 14:21h | UTC

Risk Factors for Cholangitis After Pancreatoduodenectomy: A Systematic Review – Digestive Diseases and Sciences

 

Preliminary study suggests a PEG-coated hemostatic patch reduces pancreatic fistula post-pancreatoduodenectomy

11 Apr, 2023 | 14:02h | UTC

Polyethylene glycol-coated haemostatic patch for prevention of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy: randomized clinical trial – BJS Open

 

Commentary on Twitter

 

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