Transanal Surgery: A History of taTME Ancestry.

Transanal total mesorectal excision (taTME) is the culmination of major developments in rectal cancer management and minimally invasive surgery. This surgical breakthrough holds great promise and excitement for the care of the rectal cancer patient. We would be remiss in discussing taTME to not acknowledge the role of transanal abdominal transanal proctosigmoidectomy, transanal endoluminal microsurgery, laparoscopy, and natural orifice transluminal endoscopic surgery that got us to this modern day explosion of the taTME approach. In this article, we detail and explain the convergence of these disparate experiences, how they culminated in the development of the taTME, and explore future directions in this field.

IL-7 + IL-15 are superior to IL-2 for the ex vivo expansion of 4T1 mammary carcinoma-specific T cells with greater efficacy against tumors in vivo.

Regression of established tumors can be induced by adoptive immunotherapy (AIT) with tumor draining lymph node (DLN) lymphocytes activated with bryostatin and ionomycin (B/I). Tumor antigen-sensitized DLN lymphocytes from BALB/c mice with 10-day 4T1 mammary carcinomas were harvested, activated with B/I, and expanded in culture with either interleukin-2 (IL-2) or IL-7 + IL-15. Cell yields, proliferation, phenotypes, and in vitro responses to tumor antigen were compared for cells grown in different cytokines. These T cells were also tested for antitumor activity against established 4T1 mammary carcinomas after inoculation of tumor cells subcutaneously (s.c.). IL-7/15 resulted in much faster and more prolonged proliferation of B/I-activated T cells than culturing the same cells in IL-2. This resulted in approximately 5-10-fold greater yields of viable cells. Culture in IL-7/15 yielded higher proportions of CD8(+) T cells and a higher proportion of cells with a central memory phenotype. T cells grown in IL-2 had higher interferon-gamma (IFN-gamma) release responses to tumor antigen than cells grown in IL-7/15. Adoptive transfer of B/I-activated T cells grown in IL-7/15 demonstrated much greater efficacy against 4T1 tumors in vivo. Activation of tumor antigen-sensitized T cells with B/I and culture in IL-7 + IL-15 is a promising modification of standard regimens for production of T cells for use in AIT of cancer.

Terminal ileostomy and on-table enteroscopy-A case report describing a novel approach for retrieval of foreign bodies in the difficult abdomen.

INTRODUCTION: With any abdominal surgery in a difficult abdomen, the procedure is filled with potential hazards. In addition to a prolonged operative time, there is a risk of enterotomy or damage to blood vessels and ureters. An irradiated pelvis increases this risk and may cause additional morbidity such as delayed healing. An impacted foreign body can also be a challenging problem to deal with alone but when combined with a difficult abdomen can make the problem impossible. PRESENTATION OF CASE: A 67 year-old male presented with a small bowel obstruction secondary to a foreign body impacted in the distal. The patient had a history of prostate cancer with radiation to the pelvis and thereafter developed perforated diverticulitis, requiring end colostomy. Later he underwent a colostomy take-down but developed wound infection and dehiscence resulting in an incisional hernia which was repaired. The patient failed conservative management and operative intervention was undertaken. Due to the extensive scarring of his midline abdomen, a right sided transverse incision was used. An enterotomy was made in the terminal ileum allowing the endoscope to advance to the foreign body to be retrieved with a snare. The foreign body was found to be a 3.5cm piece of bone. Post-operative course was unremarkable. DISCUSSION: Foreign body ingestion is a rare cause of small bowel obstruction, and exploration and retrieval is recommended if the obstruction does not resolve or if the bowels perforate. The method of retrieval depends on the site of the foreign body. Fortunately, in the small bowel, the terminal ileum is the narrowest part and most likely the site of impaction. Operative retrieval is easier if there are no prior abdominal interventions. An irradiated pelvis or abdomen, multiple prior procedures and a frozen abdomen warrant an alternative approach. As it can be difficult or impossible to access the ileum using a colonoscope transanally, a limited right-sided transverse incision can be employed allowing immediate access to the cecum and terminal ileum through which endoscopic retrieval could be performed. A review of the literature to date did not yield any other descriptions of this approach for foreign body retrieval, however, an appendostomy and endoscopy to rule out malignancy in patients with right sided diverticulitis has been documented. CONCLUSION: Consideration should be given to foreign body retrieval through an appendostomy or ileostomy if a midline laparotomy is considered too high risk in the setting of pelvic irradiation and multiple prior abdominal surgeries.

Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice.

Myeloid derived suppressor cells (MDSCs) accumulate in 4T1 mammary carcinoma bearing mice and present a barrier to the success of adoptive immunotherapy (AIT) by suppressing T cell immunity. In this study, we investigated the inhibition of MDSCs by gemcitabine (GEM), a chemotherapy agent that may have favorable immunologic effects. BALB/c mice were inoculated with 4T1 mammary carcinoma cells and treated with GEM either once a week starting 5 days after tumor inoculation (EARLY GEM) or as a single dose at days 20-25 (LATE GEM). Splenic mononuclear cells were isolated, activated in vitro, expanded, and stimulated with tumor antigen. T cells were then used for AIT to treat tumor-bearing mice. EARLY GEM treatment of 4T1 tumor-bearing mice significantly inhibited tumor growth, reduced splenomegaly, and significantly decreased MDSC proportion in the spleen. Support for a direct effect was demonstrated through suppression of MDSCs in spleens, bone marrow, and blood harvested 24 and 48 h after LATE GEM treatment, despite no significant decrease in tumor burden. Interestingly, treatment of tumor-bearing mice with GEM augmented in vitro expansion of splenic T cells and boosted IFN-gamma secretion in response to stimulation by tumor antigen. However, despite GEM-mediated inhibition of MDSC suppression, splenic T cells from mice with advanced tumors were ineffective in vivo against established tumors. This study provides support for direct inhibition of MDSCs and direct reduction of tumor burden by GEM in 4T1 tumor-bearing mice. GEM treatment of mice with advanced tumors improves T cell function and growth in vitro.