Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma.

The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients.

Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies?

Pancreatic exocrine insufficiency (PEI) is common amongst pancreatic cancer patients and is associated with poorer treatment outcomes. Pancreatic enzyme replacement therapy (PERT) is known to improve outcomes in pancreatic cancer, but the mechanisms are not fully understood. The aim of this narrative literature review is to summarise the current evidence linking PEI with microbiome dysbiosis, assess how microbiome composition may be impacted by PERT treatment, and look towards possible future diagnostic and therapeutic targets in this area. Early evidence in the literature reveals that there are complex mechanisms by which pancreatic secretions modulate the gut microbiome, so when these are disturbed, as in PEI, gut microbiome dysbiosis occurs. PERT has been shown to return the gut microbiome towards normal, so called rebiosis, in animal studies. Gut microbiome dysbiosis has multiple downstream effects in pancreatic cancer such as modulation of the immune response and the response to chemotherapeutic agents. It therefore represents a possible future target for future therapies. In conclusion, it is likely that the gut microbiome of pancreatic cancer patients with PEI exhibits dysbiosis and that this may potentially be reversible with PERT. However, further human studies are required to determine if this is indeed the case.

Recent Advances in Pancreatic Ductal Adenocarcinoma: Strategies to Optimise the Perioperative Nutritional Status in Pancreatoduodenectomy Patients.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy for which the mainstay of treatment is surgical resection, followed by adjuvant chemotherapy. Patients with PDAC are disproportionately affected by malnutrition, which increases the rate of perioperative morbidity and mortality, as well as reducing the chance of completing adjuvant chemotherapy. This review presents the current evidence for pre-, intra-, and post-operative strategies to improve the nutritional status of PDAC patients. Such preoperative strategies include accurate assessment of nutritional status, diagnosis and appropriate treatment of pancreatic exocrine insufficiency, and prehabilitation. Postoperative interventions include accurate monitoring of nutritional intake and proactive use of supplementary feeding methods, as required. There is early evidence to suggest that perioperative supplementation with immunonutrition and probiotics may be beneficial, but further study and understanding of the underlying mechanism of action are required.

Grynfeltt-Lesshaft lumbar hernia: a rare cause of bowel obstruction misdiagnosed as a lipoma.

Grynfeltt-Leschaft hernia is a type of lumbar hernia occurring in the superior lumbar triangle. Because of its rarity and non-specific presentation, lumbar hernia often poses a diagnostic challenge, and it can be easily misdiagnosed as a lipoma. If the correct diagnosis is missed, there is a significant risk of complications including hernia incarceration or strangulation. Here, we present a case of Grynfeltt-Lesshaft hernia which was repeatedly misdiagnosed as a lipoma and presented acutely with large bowel obstruction. A definite diagnosis was made by a computed tomography scan and the patient had emergency laparotomy and successful mesh repair of the hernia defect.

Caecum herniation through the Foramen of Winslow.

Foramen of Winslow herniation is a rare occurrence with a high mortality; it presents a diagnostic challenge with subtle clinical and radiological features. We present a case of caecal herniation through the foramen of Winslow creating a closed loop obstruction which remained undiagnosed until laparotomy. Reduction was achieved with gentle traction after first decompressing the caecum whilst still within the lesser sac.