Deepa Magge

Comparative Effectiveness of Minimally Invasive and Open Distal Pancreatectomy for Ductal Adenocarcinoma

IMPORTANCE Multicenter studies indicate that outcomes of open (ODP) and minimally invasive distal pancreatectomy (MIDP) are equivalent for benign lesions. However, data for pancreatic carcinoma are limited. OBJECTIVE To compare outcomes of ODP and MIDP for early-stage pancreatic ductal carcinoma to determine relative safety and oncologic efficacy. DESIGN Retrospective analysis of 62 consecutive patients undergoing ODP or MIDP for pancreatic ductal carcinoma by intention to treat with propensity scoring to correct for selection bias. SETTING A high-volume university center for pancreatic surgery. PARTICIPANTS Sixty-two patients at a single institution. INTERVENTIONS Patients underwent ODP or MIDP. MAIN OUTCOME MEASURES Perioperative mortality, morbidity, readmission, postoperative complications, disease progression, and overall survival. RESULTS Thirty-four patients underwent ODP, and 28 underwent MIDP with 5 conversions to ODP. No significant differences in age, body mass index, performance status, tumor size, or radiographic stage were identified. High rates of margin-negative resection (ODP, 88%; MIDP, 86%) and median lymph node clearance (ODP, 12; MIDP, 11) were achieved in both groups with equal rates and severity of postoperative complications (ODP, 50%; MIDP, 39%) and pancreatic fistula (ODP, 29%; MIDP, 21%). Despite conversions, intended MIDP was associated with reduced blood loss (P = .006) and length of stay (P = .04). Conversion was associated with a poor histologic grade and positive nodes. Median overall survival for the entire cohort was 19 (95% CI, 14-47) months. Minimally invasive distal pancreatectomy was performed increasingly in later study years and for patients with a higher Charlson-Age Comorbidity Index. Overall survival after ODP or intended MIDP was equivalent after adjusting for comorbidity and year of surgery (relative hazard, 1.11 [95% CI, 0.47-2.62]). CONCLUSIONS AND RELEVANCE We detected no evidence that MIDP was inferior to ODP based on postoperative outcomes or overall survival. This conclusion was verified by propensity score analysis with adjustment for factors affecting selection of operative technique.

Minimally Invasive Approaches to Pancreatic Surgery

Minimally invasive techniques have the potential to revolutionize the surgical management of pancreatic disease in the setting of benign and malignant processes. Pancreatic surgery, in particular, may be aided significantly by minimal access surgery given the high morbidity associated with traditional open pancreatic procedures. This article presents a review of two minimally invasive techniques for distal pancreatectomy and pancreaticoduodenectomy, focusing on metrics of technique, safety, morbidity, and oncologic outcomes and potential benefits.

Modulation of chemokines in the tumor microenvironment enhances oncolytic virotherapy for colorectal cancer

An oncolytic poxvirus such as vvDD-CXCL11 can generate potent systemic antitumor immunity as well as targeted oncolysis, yet the antitumor effect is limited probably due to limited homing to and suppressed activity of tumor-specific adaptive immune cells in the tumor microenvironment (TME). We reasoned that a chemokine modulating (CKM) drug cocktail, consisting of IFN-α, poly I:C, and a COX-2 inhibitor, may skew the chemokine (CK) and cytokine profile into a favorable one in the TME, and this pharmaceutical modulation would enhance both the trafficking into and function of antitumor immune cells in the TME, thus increasing therapeutic efficacy of the oncolytic virus. In this study we show for the first time in vivo that the CKM modulates the CK microenvironment but it does not modulate antitumor immunity by itself in a MC38 colon cancer model. Sequential treatment with the virus and then CKM results in the upregulation of Th1-attracting CKs and reduction of Treg-attracting CKs (CCL22 and CXCL12), concurrent with enhanced trafficking of tumor-specific CD8+ T cells and NK cells into the TME, thus resulting in the most significant antitumor activity and long term survival of tumor-bearing mice. This novel combined regimen, with the oncolytic virus (vvDD-CXCL11) inducing direct oncolysis and eliciting potent antitumor immunity, and the CKM inducing a favorable chemokine profile in the TME that promotes the trafficking and function of antitumor Tc1/Th1 and NK cells, may have great utility for oncolytic immunotherapy for cancer.

Complement Inhibition: A Novel Form of Immunotherapy for Colon Cancer

BackgroundComplement is a central part of both the innate and adaptive immune response and its activation has traditionally been considered part of the immunosurveillance response against cancer. Its pro-inflammatory role and its contribution to the development of many illnesses associated with inflammatory states implicate complement in carcinogenesis.MethodsWe evaluated the role of three protein inhibitors of complement—cobra venom factor, humanized cobra venom factor, and recombinant staphylococcus aureus superantigen-like protein 7—in the setting of a transplantable murine colon cancer model. Outcomes were evaluated by monitoring tumor growth, and flow cytometry, ELISPOT, and quantitative real-time PCR were used to determine the impact of complement inhibition on the host immune response.ResultsComplement inhibitors were effective at depleting complement component C3 in tumor bearing mice and this was temporally correlated with a decreased rate of tumor growth during the establishment of tumors. Treatment with cobra venom factor resulted in increased CD8+ T cells as a percentage of tumor-infiltrating cells as well as a reduced immunosuppressive environment evidenced by decreased myeloid derived suppressor cells in splenocytes of treated mice. Complement inhibition resulted in increased expression of the chemoattractive cytokines CCL5, CXCL10, and CXCL11.DiscussionComplement depletion represents a promising mode of immunotherapy in cancer by its ability to impair tumor growth by increasing the host’s effective immune response to tumor and diminishing the immunosuppressive effect created by the tumor microenvironment and ultimately could be utilized as a component of combination immunotherapy.

Gastric Adenocarcinoma in patients with Roux-en-Y Gastric bypass: A case series

/10.10 15 A mmo ence: . gedr@ The incidence of gastric cancer is approximately 24,000 cases per year with a mortality of 14,000 cases per year. There has been an increasing incidence of proximal gastric cancer and gastroesophageal junction cancer in the United States over the past 5–10 years [1]. Gastric cancer in patients who had previously undergone gastric restrictive surgery and gastric bypass has been reported but is rare. Seventeen case reports and series have been performed describing patients with gastric cancer after undergoing gastric bypass surgery [2]. In the majority of patients who had undergone previous Roux-en-Y gastric bypass surgery, gastric cancer developed in the excluded stomach, leading to delayed diagnosis. Unfortunately, management for these patients is difficult, given their often late diagnoses, which results in the advanced nature of their cancers when symptoms eventually develop [2]. Two cases of gastric adenocarcinoma in patients after Roux-en-Y gastric bypass will be described.

Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival.

Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis (P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement (P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival (P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

Hyperthermic intraperitoneal chemoperfusion as a component of multimodality therapy for ovarian and primary peritoneal cancer

The role of hyperthermic intraperitoneal chemoperfusion (HIPEC) in the multimodality treatment of ovarian peritoneal metastases (OPM) and primary peritoneal cancer (PPC) remains controversial. We hypothesized that cytoreductive surgery (CRS) and HIPEC would provide meaningful survival benefit without excessive morbidity.

Minimally Invasive Pancreas Surgery

Abstract The introduction of laparoscopy in the 1980s has revolutionized the field of complex abdominal surgery. Traditional operations for almost all pancreatic resections and reconstructions have been described and replicated through a laparoscopic approach. Minimally invasive pancreatic surgeries are now well integrated into routine pancreatic resections and reconstructions at high-volume centers, with equivalent rates of mortality compared with open procedures. With the advent of robotic assistance, patients benefit from less intraoperative blood loss, expedited functional recovery, and shorter hospital stays. Meanwhile, surgeons benefit from binocular three-dimensional vision, scaling, stabilization of tremor, reduced operator fatigue, and improved ergonomics from the console-surgeon interface. This chapter will focus on the robotic approach, summarizing the data on the safety, efficacy, and technique of robotic approaches to minimally invasive pancreas surgery for both benign and malignant indications, showcasing the diversity of the platform for complex pancreatic operations.

Performing the Difficult Cholecystectomy Using Combined Endoscopic and Robotic Techniques: How I Do It

Laparoscopic cholecystectomy is the standard of care for cholelithiasis as well as cholecystitis. However, in the setting of Mirizzi syndrome or gangrenous cholecystitis where the critical view cannot be ascertained, subtotal cholecystectomy may be necessary. Using the robot-assisted approach, difficult cholecystectomies can be performed upfront without need for partial cholecystectomy. Even in the setting of Mirizzi syndrome where severe scarring and fibrosis are evident, definitive cholecystectomy and takedown of the cholechystocholedochal fistula can be performed in a safe and feasible fashion following successful endoscopic common bile duct stent placement. The purposes of this report are to review the history of Mirizzi syndrome as well as its traditional and novel treatment techniques and highlight technical pearls of the robotic approach to this diagnosis.

Minimally Invasive Surgery for Pancreatic Head Cancer

An increasing number of reports on minimally-invasive pancreaticoduodenectomy (MIPD) have emerged over the last two decades. Morbidity, oncologic outcomes, and the impact of the learning curve for MIPD are being carefully scrutinized to ensure that safety and efficacy are not compromised, particularly in the setting of periampullary malignancies. Although many of the current adopters of MIPD are still within their learning curve, a number of single institutional series have recently confirmed the non-inferiority of the laparoscopic or robotic PD when performed by experienced pancreatic surgeons at high volume centers. In the absence of randomized controlled trials to address the safety, efficacy and potential advantages of the MIPD, this chapter will examine the available retrospective data on the safety and oncologic oncologic outcomes of the laparoscopic and robotic PD for pancreatic head malignancies.