Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer.

Background: Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC). Methods: We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC. Results: One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival. Conclusions: Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.

Radioimmunoconjugates in the age of modern immuno-oncology.

Immunotherapy was first investigated as a therapeutic option for treating cancer more than a century ago. During this period, it has gone through numerous disappointments when the successes obtained in the laboratory were not matched clinically. However, recent advances in immuno-oncology have provided the impetus to revisit this therapeutic option. Unlike previous efforts, modern immunotherapy is now a realistic and formidable therapeutic option for patients with relapsed/refractory malignancies. Unfortunately, most of the successes obtained thus far have primarily been in patients with hematologic malignancies. While the results of immunotherapy with immune check-point inhibitors for solid tumors such as non-small cell lung cancer and melanoma are encouraging, more effective treatment methods are desirable. Many intrinsic and extrinsic factors pose as obstacles to successful immunotherapy of solid tumors. They include heterogeneity of tumor antigens, limitation in the trafficking and accessibility of the effector mechanisms to the tumor sites, the adverse anti-inflammatory tumor microenvironment, and the on-target off tumor and off-target off-tumor effects of some of these approaches. In this review, we will discuss these obstacles and examine the evidence that support the notion that radioimmunotherapy, using radioimmunoconjugates, may be the answer to overcome these obstacles in patients with metastatic cancer. Finally, we will discuss how the efficacy of radioimmunotherapy using radioimmunoconjugates might further be harnessed to maximize successes in these patients.

Hemosuccus Pancreaticus: A Serious Complication of Chronic Pancreatitis.

Hemosuccus pancreaticus is a rare cause of gastrointestinal bleeding that usually presents with melena and abdominal pain. It is defined as a hemorrhage from the ampulla of Vater passing through the main pancreatic duct toward the second portion of the duodenum. Imaging is usually required to establish a diagnosis, and angiography continues to be the gold standard for both treatment and diagnosis. In some instances where bleeding is uncontrolled or if the patient is unstable, surgery may be required. Physicians should have a high index of suspicion, especially in patients with a history of chronic pancreatitis, as this diagnosis is associated with a very high mortality rate if left untreated. We report a case of a 67-year-old male with a known history of chronic pancreatitis and pancreatic pseudocyst who presented with melena and right upper quadrant abdominal pain and was found to have hemosuccus pancreaticus secondary to a gastroduodenal artery bleed. He underwent successful angiographic embolization and was discharged home after ensuring resolution of bleed and improvement in symptoms.

Piperacillin/Tazobactam and Meropenem Use Increases the Risks for Acute Graft Rejection Following First Kidney Transplantation.

Many broad-spectrum antibiotics (BSA) alter the intestinal microbiome that regulates adaptive immune responses. We hypothesized that BSA use before and early after kidney transplant may affect acute graft rejection (AGR). We carried out a retrospective cohort study on all patients who underwent kidney transplants in our institution. Patient demographics, clinical data, diagnosis, and treatment history were collected. Antibiotic use within 2 months prior to transplant and during the hospital admissions for transplant, as well as antibiotic types were recorded. A total of 357 consecutive first transplants were included for analysis. Median age was 52 years (range 7-76). A total of 67 patients received living donor and 290 deceased donor kidneys. A total of 19 patients received BSA within two months prior to transplant and 55 patients during the hospital admission for the transplant. With a median follow-up of 1270 days, 38 episodes of biopsy-proven AGR were recorded. There was no difference in the AGR rates during the first year between patients who received BSA and those who did not. However, the use of piperacillin/tazobactam or meropenem (PM) was associated with increased risks for the development of AGR, irrespective of the source of the donor grafts. Time to development of AGR was also shorter. Our data, therefore, suggest that the use of PM BSA prior to and immediately after kidney transplant increases the risks for AGR.

Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice.

Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.