Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.

The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.

Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management.

Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration.

Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Patients at High Risk of Developing Gallbladder Cancer Peritoneal Metastases: Case Report and Rationale for a Prospective Clinical Trial.

Gallbladder cancer is a devastating disease with a 5-year survival of only 18%. The majority of gallbladder cancers are discovered incidentally in patients undergoing cholecystectomy. During non-oncologic laparoscopic cholecystectomy for gallbladder disease, gallbladder perforation occurs in 29% of cases and spillage of gallstones occurs in 9% of cases. Patients with gallbladder cancer frequently develop peritoneal recurrence, particularly after intra-operative bile spillage during cholecystectomy for incidental gallbladder cancer. The high likelihood of spillage and peritoneal seeding during cholecystectomy for incidental gallbladder cancer suggests the need for prophylactic strategies to prevent peritoneal carcinomatosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing cytoreductive surgery and has been associated with a survival advantage in a multi-institutional retrospective case series. However, the utilization of HIPEC with a prophylactic intent against the development of peritoneal disease following resection of gallbladder cancer has not yet been prospectively studied. Here, we review the literature surrounding gallbladder cancer and HIPEC, report an institutional experience utilizing prophylactic HIPEC, and discuss a recently proposed prospective clinical trial evaluating the efficacy of prophylactic HIPEC in the prevention of gallbladder peritoneal metastasis.

Recent advances for treatment of upper gastrointestinal malignancy.

Recent prospective trials for esophageal cancer, gastric cancer, and gastrointestinal stromal tumor (GIST) are encouraging. This manuscript reviews selected recently published studies. Not surprisingly, immunotherapy dominates the current clinical trial landscape. However, targeted biologic therapies and standard chemotherapy remain critical to the treatment of gastric and esophageal cancer while imatinib remains the backbone for advanced or metastatic GISTs. For all three cancers, surgical resection remains important when intent of treatment is potential cure.

Current and future imaging modalities in gastric cancer.

Gastric adenocarcinoma treatment can include endoscopic mucosal resection, surgery, chemotherapy, radiation, and palliative measures depending on staging. Both invasive and noninvasive staging techniques have been used to dictate the best treatment pathway. Here, we review the current imaging modalities used in gastric cancer as well as novel techniques to accurately stage and screen these patients.

A Rare Presentation of Ileocecal Mucormycosis in a Heart Transplant Recipient.

Mucorales is an order of angioinvasive fungi that classically infects immunocompromised patients. As an aerogenous pathogen, it most frequently causes disease of the lungs and paranasal sinuses. Gastrointestinal mucormycosis represents a particularly rare site of infection. This case report describes the complicated presentation of ileocecal mucormycosis in an immunocompromised orthotopic heart transplant recipient. The diagnosis was made status-post ileocolonic resection, and the patient was promptly started on liposomal amphotericin B and micafungin. Unfortunately, the patient ultimately succumbed to disseminated infection. In this study, we review the epidemiology, the presenting features of gastrointestinal mucormycosis, and emphasize the prompt initiation of therapy on suspected disease.

B cell signatures of BCWD-resistant and susceptible lines of rainbow trout: a shift towards more EBF-expressing progenitors and fewer mature B cells in resistant animals.

Bacterial cold water disease (BCWD) is a chronic disease of rainbow trout, and is caused by the Gram-negative bacterium Flavobacterium psychrophilum (Fp), a common aquaculture pathogen. The National Center for Cool and Cold Water Aquaculture has bred two genetic lines of rainbow trout: a line of Fp-resistant trout (ARS-Fp-R or R-line trout) and a line of susceptible trout (ARS-Fp-S, or S-line). Little is known about how phenotypic selection alters immune response parameters or how such changes relate to genetic disease resistance. Herein, we quantify interindividual variation in the distribution and abundance of B cell populations (B cell signatures) and examine differences between genetic lines of naive animals. There are limited trout-specific cell surface markers currently available to resolve B cell subpopulations and thus we developed an alternative approach based on detection of differentially expressed transcription factors and intracellular cytokines. B cell signatures were compared between R-line and S-line trout by flow cytometry using antibodies against transcription factors early B cell factor-1 (EBF1) and paired domain box protein Pax5, the pro-inflammatory cytokine IL-1ß, and the immunoglobulin heavy chain mu. R-line trout had higher percentages of EBF(+) B myeloid/ progenitor and pre-B cells in PBL, anterior and posterior kidney tissues compared to S-line trout. The opposite pattern was detected in more mature B cell populations: R-line trout had lower percentages of both IgM(+) mature B cells and IgM-secreting cells in anterior kidney and PBL compared to S-line trout. In vitro LPS-activation studies of PBL and spleen cell cultures revealed no significant induction differences between R-line and S-line trout. Together, our findings suggest that selective resistance to BCWD may be associated with shifts in naive animal developmental lineage commitment that result in decreased B lymphopoiesis and increased myelopoiesis in BCWD resistant trout relative to susceptible trout.