Case report: Case series featuring anastomotic colonic adenocarcinoma following jejunoileal bypass requiring oncologic resection and jejunoileal bypass reversal.

Like all surgical fields, bariatric surgery has evolved immensely, so much so that previous procedures are now obsolete. For instance, the jejunoileal bypass has fallen out of favor after severe metabolic consequences resulted in prolonged morbidity and even mortality. Despite this, several patients persevered long enough to develop other pathology, such as cancer. This progression has been validated in animal models but not human patients. Nonetheless, contemporary surgeons may encounter situations where they must resect and re-establish intestinal continuity in patients with this antiquated anatomy. When faced with this scenario, the question of whether or not the previously bypassed small bowel can be safely reunited plagues the surgeon remains unanswered. Unfortunately, the literature does not effectively answer this question, even anecdotally through case reports or series. Therefore, we share our experience with three patients who developed colon cancer following jejunoileal bypass and subsequently underwent oncologic resection with simultaneous reversal of their jejunoileal bypasses.

Retrospective Review of Outcomes in Non-Invasive Mucinous Appendiceal Neoplasms with and without Peritoneal Spread: A Cohort Study.

Patients treated surgically for local non-invasive mucinous appendiceal neoplasm (NI-MAN) may recur with the development of peritoneal dissemination (PD). The risk of recurrence and predictive factors are not well studied. Patients with NI-MAN, with or without peritoneal dissemination at presentation, were included. Patients with limited disease underwent surgical resection only. Patients with peritoneal dissemination underwent cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Patients without PD (nPD) were compared to those who presented with PD. Thirty-nine patients were included, 25 in nPD and 14 in PD. LAMN was diagnosed in 96% and 93% of patients in nPD and PD, respectively. Acellular mucin on the peritoneal surface was seen in 16% of nPD patients vs. 50% of PD patients (p = 0.019). Two (8%) patients in the nPD group who had LAMN without wall rupture recurred, at 57 and 68 months, with a PCI of 9 and 22. The recurrence rate in the PD group was 36%. All recurred patients underwent CRS+HIPEC. A peritoneal recurrence is possible in NI-MANs confined to the appendix even with an intact wall at initial diagnosis. The peritoneal disease may occur with significant delay, which is longer than a conventional follow-up.

Intra-arterial Versus Intravenous Adoptive Cell Therapy in a Mouse Tumor Model.

Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue. We examined the route of administration as a potential modifier of both trafficking and antitumor efficacy. Femoral artery cannulation and tail vein injection for the intra-arterial (IA) and IV delivery, respectively, were utilized in the B16-OVA/OT-I mouse model system. Both IV and IA infusions showed decreased tumor growth and prolonged survival. However, although significantly increased T-cell tumor infiltration was observed in IA mice, tumor growth and survival were not improved as compared with IV mice. These studies suggest that IA administration produces increased early lymphocyte trafficking, but a discernable survival benefit was not seen in the murine model examined.

Association of Frailty With Failure to Rescue After Low-Risk and High-Risk Inpatient Surgery.

Importance: Failure to rescue (FTR), or death after a potentially preventable complication, is a nationally endorsed, publicly reported quality measure. However, little is known about the impact of frailty on FTR, in particular after low-risk surgical procedures. Objective: To assess the association of frailty with FTR in patients undergoing inpatient surgery. Design, Setting, and Participants: This study assessed a cohort of 984 550 patients undergoing inpatient general, vascular, thoracic, cardiac, and orthopedic surgery in the National Surgical Quality Improvement Program between January 1, 2005, and December 31, 2012. Frailty was assessed using the Risk Analysis Index (RAI), and patients were stratified into 5 groups (RAI score, ≤10, 11-20, 21-30, 31-40, and >40). Procedures were categorized as low mortality risk (≤1%) or high mortality risk (>1%). The association between RAI scores, the number of postoperative complications (0, 1, 2, or 3 or more), and FTR was evaluated using hierarchical modeling. Main Outcomes and Measures: The number of postoperative complications and inpatient FTR. Results: A total of 984 550 patients were included, with a mean (SD) age of 58.2 (17.1) years; women were 549 281 (55.8%) of the cohort. For patients with RAI scores of 10 or less, major complication rates after low-risk surgery were 3.2%; rates of those with RAI scores of 11 to 20, 21 to 30, 31 to 40, and more than 40 were 8.6%, 13.5%, 23.8%, and 36.4%, respectively. After high-risk surgery, these rates were 13.5% for those with scores of 10 or less, 23.7% for those with scores of 11 to 20, 31.1% for those with scores of 21 to 30, 42.5% for those with scores of 31 to 40, and 54.4% for those with scores of more than 40. Stratifying by the number of complications, significant increases in FTR were observed across RAI categories after both low-risk and high-risk procedures. After a low-risk procedure, odds of FTR after 1 major complication for patients with RAI scores of 11 to 20 increased 5-fold over those with RAI scores of 10 or less (odds ratio [OR], 5.3; 95% CI, 3.9-7.1). Odds ratios were 8.1 (95% CI, 5.6-11.7) for patients with RAI scores of 21 to 30; 22.3 (95% CI, 13.9-35.6) for patients with scores of 31 to 40; and 43.9 (95% CI, 19-101.1) for patients with scores of more than 40. For patients undergoing a high-risk procedure, the corresponding ORs were likewise consistently elevated (RAI score 11-20: OR, 2.5; 95% CI, 2.3-2.7; vs RAI score 21-30: 5.1; 95% CI, 4.6-5.5; vs RAI score 31-40: 8.9; 95% CI, 8.1-9.9; vs RAI score >40: 18.4; 95% CI, 15.7-21.4). Conclusions and Relevance: Frailty has a dose-response association with complications and FTR, which is apparent after low-risk and high-risk inpatient surgery. Systematic assessment of frailty in preoperative patients may help refine estimates of surgical risk that could identify patients who might benefit from perioperative interventions designed to enhance physiologic reserve and potentially mitigate aspects of procedural risk, and would provide a framework for shared decision-making regarding the value of a given surgical procedure.

Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review and Meta-analysis of Major Abdominal Surgery.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures. BACKGROUND: ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols. METHODS: A systematic review was performed using "enhanced recovery after surgery" or "fast track" as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs. RESULTS: A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI: $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis. CONCLUSIONS: ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.

Water lavage as an adjunct to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

BACKGROUND: Water lavage (WL) during gastrointestinal cancer surgery has osmotically mediated lytic effects on tumor cells. We investigated the safety and efficacy of WL with CRS-HIPEC. METHODS: This is a retrospective review, 1/2003-7/2014, of a single institution experience with CRS-HIPEC comparing patients who had WL (WL+) to those who did not (WL-). RESULTS: Of 157 CRS-HIPECs, 16 (10.2%) were WL+. WL+ had more PCI scores >20 compared to WL- (56.3% vs 19.4%, respectively, p = 0.003); however, the completeness of cytoreduction (CC) was similar. There were no differences in hospital length of stay or post-operative complications. The average POD 1 sodium (Na) level was statistically lower in the WL+ group (133.6 ± 2.5 vs 135.5 ± 3.2 mEq/L, p = 0.023); however, the average Na at discharge for each group was 140 mEq/L. There were no differences in 3-year OS (3WL+:0.63 vs WL-:0.68, p = 0.97) or RFS (WL+:0.32 vs WL-:0.39, p = 0.47). A subset analysis for patients with PCI >20 showed no difference between groups. CONCLUSIONS: WL offers a low cost, safe and theoretically efficacious method of tumor cell lysis for peritoneal malignancy.

Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy.

A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer.

T Cells Derived From Human Melanoma Draining Lymph Nodes Mediate Melanoma-specific Antitumor Responses In Vitro and In Vivo in Human Melanoma Xenograft Model.

It has been established in murine models that lymph nodes draining a progressively growing tumor contain antigen-specific T cells capable of mediating protective immune responses upon adoptive transfer. However, naturally occurring human tumor-draining lymph nodes (TDLNs) have yet to be fully investigated. In this study, we analyzed TDLNs from patients with stage III melanoma who were undergoing routine lymph node dissection. Following short-term (14 d) culture activation with anti-CD3/anti-CD28 microbeads and expansion in low concentrations of IL-2, the melanoma-draining lymph node (MDLN) cells were ∼ 60% CD4-activated and ∼ 40% CD8-activated T cells. The activated MDLN cells demonstrated reactivity in response to overlapping peptides spanning the sequence of 4 different known melanoma antigens MAGEA1, Melan-A/MART-1, NY-ESO-1, and Prame/OIP4, suggesting the presence of melanoma-specific T cells. Coculture of activated MDLN T cells with cancer cells in vitro resulted in preferential apoptosis of human cancer cell lines that were cocultured with T cells with high degree of MHC matching. Adoptive transfer of MDLN T cells with high degree of MHC matching to A375 to mice-bearing human A375 melanoma xenografts resulted in dose-dependent improvement in survival. Although prior human studies have demonstrated the immune responses within melanoma vaccine-draining lymph nodes, this study presents evidence for the first time that naturally occurring human MDLN samples contain melanoma-experienced CD4 and CD8 T cells that can be readily cultured and expanded to mediate protective immune responses both in vitro and in vivo in a human melanoma xenograft model.

Expansion of melanoma-specific T cells from lymph nodes of patients in stage III: implications for adoptive immunotherapy in treating cancer.

BACKGROUND: Adoptive immunotherapy for patients with metastatic melanoma has yielded encouraging results. However, methods of expanding melanoma-specific T cells from stage III are limited. The objective of this study was to determine whether melanoma-specific T cells could be generated from the melanoma-draining lymph nodes (MDLNs) of patients in stage III. METHODS: Patients in stage III who were undergoing completion lymphadenectomy were enrolled into a protocol approved by the institutional review board. MDLN cells were tested for ability to undergo cryopreservation, expand ex vivo in IL-2 or IL-2 and IL-7, and mediate melanoma-specific antitumor responses in vitro. RESULTS: Cryopreservation produced no significant differences from fresh cultures in terms of cell growth and cellular phenotype. IL-2 and IL-2/IL-7 cultures resulted in similar growth rates, and functional studies revealed the presence of T cells that secreted interferon gamma in response to melanoma antigen peptides. Both IL-2- and IL-2/IL-7-cultured MDLN cells mediated significant apoptosis of human melanoma cell lines as compared to breast and brain tumor lines in vitro. Overall, there did not seem to be a benefit of adding IL-7. Both CD4+ and CD8+ T cells appear to mediate tumor cell apoptosis. CONCLUSION: This study demonstrates that melanoma antigen-specific T cells can be generated from regional melanoma-draining lymph nodes and expanded ex vivo from patients with stage III disease.

Positron emission tomography for benign and malignant disease.

Functional imaging using radiolabeled probes that specifically bind and accumulate in target tissues has improved the sensitivity and specificity of conventional imaging. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) has shown improved diagnostic accuracy in differentiating benign from malignant lesions in the setting of solitary pulmonary nodules. FDG-PET has become useful in preoperative staging of patients with lung cancer, and is being tested with many other malignancies for its ability to change patient management. This article provides an overview of the current status of FDG-PET and presents the challenges of moving toward routine use.