Use of Robotic Technology in the Management of Complex Colorectal Pathology.

Use of robotic surgery is increasing in multiple surgical specialties including colorectal. We argue that the improved visualization and better instrumentation outweigh the increased cost and operating room time. However, the indications for its use are not clearly defined. This is especially true in complex pathologies such as rectal cancer and complicated diverticulitis. We explore the limited clinical data on the subject to support or dismiss the use of this currently developing technology.

True NOTES TME resection with splenic flexure release, high ligation of IMA, and side-to-end hand-sewn coloanal anastomosis.

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) represents the ultimate expression of minimally invasive surgery. We have developed and present here an initial feasibility and safety study of transanal total mesorectal excision (TME) with splenic flexure release, high ligation of the IMA and IMV, and side-to-end coloanal anastomosis with temporary diverting ileostomy for rectal cancer. METHODS: A program of full NOTES TME resection with release of the splenic flexure, high ligation of the IMA/IMV, with side-to-end coloanal anastomosis was performed transanally from December 2013 to July 2014. Demographics, preoperative, perioperative, and postoperative data were prospectively obtained. Operative components were broken into TME, colonic mobilization, splenic flexure release, IMA/IMV transection, transanal extraction of specimen, and coloanal anastomosis for analysis of performance completion. RESULTS: There were 3 women and 1 man on whom we operated. Mean age was 56 (46-65). Mean BMI was 26 (23.8-30.2). The operation was completed entirely transanally in 2 patients. Transanal component completion of the operation was as follows: TME in 3/4; colonic mobilization in 4/4; splenic flexure release in 3/4; IMA/IMV transection in 3/4; transanal specimen extraction in 4/4; coloanal anastomosis in 4/4. Abdominal time for completion of component parts was: splenic flexure release 4:53 (min:s), IMA/IMV 19:43, completion of TME 13:41. Mean EBL was 194 cc (25-500). Aside from stoma site, there were no abdominal incisions. There were no mortalities. Mesorectum was intact in all 4 patients and with negative circumferential and distal margins. CONCLUSION: This experience supports the feasibility and safety of a true NOTES TME. The critical anatomic views demonstrated on video affirm the potential of this approach for distal rectal cancer. Colorectal surgery represents the most logical application for NOTES. While highly promising, a great deal of work remains to develop the technique and applicability of NOTES colorectal surgery.

Single-port laparoscopic colorectal surgery shows equivalent or better outcomes to standard laparoscopic surgery: results of a 190-patient, 7-criterion case-match study.

INTRODUCTION: Single-port (SP) surgery has been characterized as having limited applicability regarding procedure, disease, and patient characteristics. There is a question if SP procedures offer disadvantages or advantages to multiport (MP) colorectal surgery. We hypothesize that SP is equivalent to MP and is a safe alternative in the full spectrum of colorectal disease and procedures. METHODS: A case-matched analysis of a prospectively maintained database to compare perioperative outcomes in SP versus MP was performed. Criteria included age, gender, BMI, previous abdominal surgery, previous XRT, disease process, and procedure. 95 exact matches for all 7 criteria were found between 159 SP and 1,617 MP cases. Perioperative outcomes, surgical technique, morbidity, mortality, local recurrence, and 5-year survival were analyzed. RESULTS: There was lower mean EBL in SP but no difference in transfusion requirement. OR time for SP left colectomy was shorter, with a trend to shorter OR times found in all procedures. 99 % SP and 98 % MP had no intra-operative complications. Conversion to open was equivalent (0/1). Mean largest incision was smaller for SP. There were no differences in return of bowel function or length of hospital stay. There were no mortalities. There were no differences in perioperative morbidity, local recurrence, distant metastasis, or overall 5-year survival. CONCLUSIONS: SP is a safe alternative to MP colorectal surgery across the full array of procedures in equivalent patients. This study demonstrates SP has less blood loss, smaller incisions, is quicker in left colectomy, and tends to be quicker across all procedures. Conversion and morbidity rates are equivalent to MP, without compromise in quality of surgical technique. While proper training is essential, concerns regarding the inability to use SP laparoscopic colorectal surgery safely are unfounded in nearly exactly matched patients. These issues will require further study as SP laparoscopic colorectal surgery is practiced more widely.

Segmental versus extended resection for sporadic colorectal cancer in young patients.

BACKGROUND AND OBJECTIVES: Guidelines on the management of colon cancer state that extensive colectomy should be "considered" for patients of young age (<50). This study aimed to compare the risk of metachronous cancer, overall recurrence and mortality between segmental and extended colon resections in patients under the age of 50 with sporadic CRC. METHODS: We performed a retrospective review of patients age <50 undergoing surgery for CRC from 1991 to 2009. Patients were divided into two groups based on extent of resection: segmental versus extended. The primary outcomes analyzed were metachronous tumors, disease recurrence, and overall survival. RESULTS: Two hundred seventy one patients underwent segmental resection and 30 underwent extended resection. 3.3% in the segmental resection group developed metachronous CRC versus 0% in the extended resection group (P = 0.61). There was no significant difference in the risk of recurrence or mortality for those who underwent a segmental resection compared to those with an extended resection. In a regression model, type of surgery was not an independent risk factor for recurrence or mortality. CONCLUSIONS: Extended colectomy for sporadic CRC in patients younger than 50 does not improve disease-free or overall survival. Further study to determine if segmental resection is appropriate oncologic treatment is warranted.

Impact of Hospital Volume on Utilization of Minimally Invasive Surgery for Gastric Cancer.

BACKGROUND: Minimally invasive surgery (MIS) for gastric cancer is increasingly performed. The purpose of this study is to evaluate trends in utilization of laparoscopic and robotic techniques compared to open surgery as well as utilization based on hospital volume. METHODS: We used the National Cancer Database to query patients who underwent gastrectomy from 2010 to 2017 for adenocarcinoma. Regression analyses were used to determine associations between MIS and clinical factors, the trend of MIS over time, and survival. RESULTS: A total of 18,380 patients met inclusion criteria. The annual rates of MIS increased for all hospital volumes, though lower volume centers were less likely to undergo MIS. MIS was associated with a shorter length of stay compared to open, and robotic gastrectomy had a higher rate of obtaining at least 15 lymph nodes and lower rate of having a positive margin. CONCLUSIONS: MIS utilization for resection of gastric cancer increased over time, with robotic surgery increasing at a higher rate than laparoscopic surgery. Importantly, this occurred without increased in mortality or sacrificing adequate oncologic outcomes.

A Rare Case of Pancreatic Endometriosis Masquerading as Pancreatic Mucinous Neoplasm.

Endometriosis is a relatively common condition among women, and pancreatic endometriosis has been reported on rare occasions. Such pancreatic lesions are difficult to diagnose and distinguish from other cystic lesions of the pancreas preoperatively. This report describes a case of pancreatic endometriosis in a 51-year-old female patient. Imaging demonstrated an enlarging cyst with findings concerning for a mucinous neoplasm. The patient underwent robotic distal pancreatectomy and splenectomy. Histopathology revealed an endometriotic cyst. Pancreatic endometriosis can be difficult to distinguish from other lesions of the pancreas. Surgical resection should be undertaken in cases where malignancy is suspected.

A Unique Presentation of Metastatic Gallbladder Carcinoma.

Gallbladder carcinoma can be challenging to diagnose and treat and usually leads to poor outcome, due to its aggressive nature and the nonspecific clinical presentation at early stage. We describe an interesting case of a 60-year-old female who presented with stage 3 appendiceal carcinoma after appendectomy was performed outside hospital. Further imaging workup demonstrated enlarged ovarian cysts and porcelain gallbladder. Upon exploration, she was found to have carcinomatosis and we proceeded with cytoreductive surgery (CRS) and hyperthermic intraperitoneal therapy (HIPEC). Final pathology demonstrated carcinoma from gallbladder primary.

Closed Loop Obstruction from Epiploic Appendage Adhesion Mimicking Pericecal Internal Hernia.

Internal hernias involve herniation of viscera into an abdominal compartment through a defect in the mesentery or peritoneum. Herniation may occur through normal anatomic structures or through pathologic defects secondary to congenital abnormality, inflammation, trauma, or surgery. Patients with an internal hernia most commonly present with acute bowel obstruction. While internal hernia is an uncommon cause of bowel obstruction, making up approximately 0.2-0.9% of cases (Choi, 2017), the incidence is increasing due to greater use of techniques such as Roux-en-Y for liver transplant and gastric bypass. There are multiple types of internal hernia, including paraduodenal, Foramen of Winslow, sigmoid mesocolon, pericecal, transmesenteric, transomental, supravesical, and pelvic. We present a case in which a transverse colon epiploic appendage adhesion to the ascending colon mesentery resulted in a closed loop obstruction mimicking a pericecal internal hernia. Radiologists should be aware of the imaging findings of closed loop obstruction related to internal hernia and maintain a high index of suspicion in patients with history of prior abdominal surgery presenting with bowel obstruction. It is useful for radiologists to understand that adhesions may result in internal hernias, which mimic the classically described categories.

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO).

Dendritic cells (DCs) possess the unique abilities to initiate a primary immune response and to present antigens to naïve T lymphocytes. Recently, there has been a rapidly growing interest in the use of DCs in active specific immunotherapy (ASI) for the treatment of patients with cancer. In the present study, we determined the ability of DCs to express Melanoma-Associated Antigens (MAAs) from a polyvalent Melanoma Vaccine (DC-MelVac; Patent #11221/5) developed in our facility. The vaccine consists of a recombinant IL-2 gene-encoded vaccinia melanoma oncolysate (rIL-2VMO) derived from an established human melanoma cell line. Our results show that r-IL2VMO-pulsed DCs express MAAs presented by the Mel-2 melanoma cell line oncolysate used in this study. We believe that these promising results will prove useful as an active specific immunotherapeutic agent for patients with Stage III melanoma.

Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development.

HuR is a ubiquitous nucleocytoplasmic RNA-binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur (IKO) mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of Apc(min/+) mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a three-fold decrease in tumor burden characterized by reduced proliferation, increased apoptosis, and decreased expression of transcripts encoding antiapoptotic HuR target RNAs. Similarly, Hur(IKO) mice subjected to an inflammatory colon carcinogenesis protocol [azoxymethane and dextran sodium sulfate (AOM-DSS) administration] exhibited a two-fold decrease in tumor burden. Hur(IKO) mice showed no change in ileal Asbt expression, fecal bile acid excretion, or enterohepatic pool size that might explain the phenotype. Moreover, none of the HuR targets identified in Apc(min/+)Hur(IKO) were altered in AOM-DSS-treated Hur(IKO) mice, the latter of which exhibited increased apoptosis of colonic epithelial cells, where elevation of a unique set of HuR-targeted proapoptotic factors was documented. Taken together, our results promote the concept of epithelial HuR as a contextual modifier of proapoptotic gene expression in intestinal cancers, acting independently of bile acid metabolism to promote cancer. In the small intestine, epithelial HuR promotes expression of prosurvival transcripts that support Wnt-dependent tumorigenesis, whereas in the large intestine epithelial HuR indirectly downregulates certain proapoptotic RNAs to attenuate colitis-associated cancer. Cancer Res; 74(18); 5322-35. ©2014 AACR.

Liver fatty acid-binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice.

Evidence suggests a relationship between dietary fat intake, obesity, and colorectal cancer, implying a role for fatty acid metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid-binding protein (L-Fabp), a dominant intestinal fatty acid-binding protein, regulates intestinal fatty acid trafficking and metabolism, and L-Fabp deletion attenuates diet-induced obesity. Here, we examined whether changes in intestinal fatty acid metabolism following L-Fabp deletion modify adenoma development in Apc(Min)(/+) mice. Compound L-Fabp(-/-)Apc(Min)(/+) mice were generated and fed a 10% fat diet balanced equally between saturated, monounsaturated, and polyunsaturated fat. L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in adenoma number and total polyp area compared with Apc(Min)(/+)controls, reflecting a significant shift in distribution toward smaller polyps. Adenomas from L-Fabp(-/-)Apc(Min)(/+) mice exhibited reductions in cellular proliferation, high-grade dysplasia, and nuclear ß-catenin translocation. Intestinal fatty acid content was increased in L-Fabp(-/-)Apc(Min)(/+) mice, and lipidomic profiling of intestinal mucosa revealed significant shifts to polyunsaturated fatty acid species with reduced saturated fatty acid species. L-Fabp(-/-)Apc(Min)(/+) mice also showed corresponding changes in mRNA expression of enzymes involved in fatty acid elongation and desaturation. Furthermore, adenomas from L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in mRNA abundance of nuclear hormone receptors involved in cellular proliferation and in enzymes involved in lipogenesis. These findings collectively implicate L-Fabp as an important genetic modifier of intestinal tumorigenesis, and identify fatty acid trafficking and metabolic compartmentalization as an important pathway linking dietary fat intake, obesity, and intestinal tumor formation.

Totally robotic single-position 'flip' arm technique for splenic flexure mobilizations and low anterior resections.

BACKGROUND: Using the da Vinci robot in low anterior resection (LAR) has not been widely adopted due to limited range of motion of the robotic arms and the need to move the robot during operations. Our technique uses all three arms for both the splenic flexure and the pelvis, but with only one docking position. METHODS: The robot is placed to the left of the patient. The camera port is 3 cm to the right of the umbilicus. Arm 1 is placed in the RLQ. Arm 2 is placed midepigastric. Arm 3 is placed in the LLQ. Arm 3 starts off on the left side of the robot, on the same side as Arm 1 aimed cephalad. During mobilization of colon and splenic flexure, Arms 2 and 3 help retract the colon while Arm 1 dissects. Our pelvic dissection begins with Arm 3 "flipped" to the right side of the robot and redocked to the same left sided port aimed caudally. The robot does not need to be repositioned and the patient does not need to be moved. The pelvic dissection can now be done in the standard fashion. RESULTS: Our early experience includes four patients: two LARs and two left hemicolectomies. Mean operative time = 347 minutes, docking time = 20 minutes, and robotic surgical time = 195 minutes. Two complications occurred: post-operative ileus and high ostomy output. Mean LOS = 5. CONCLUSIONS: The robotic "flip" arm technique allows the surgeon to fully utilize all the robotic arms in LAR, which is unique versus other techniques.

Subungual squamous cell carcinoma of the toe: working toward a standardized therapeutic approach.

Subungual squamous cell carcinoma (SCC) is a rare malignancy with very few reported cases that occur on the toe. The etiology of these lesions is not known, and although this location is generally considered low risk for metastasis, cases of inguinal lymph node metastasis after toe amputation have been reported. Patients with subungual disease may meet criteria other than location that increase their risk for metastasis. Currently, no standardized approach to therapy for these patients has been established. In this article, we describe a patient with SCC of the right fourth toe with no clinical evidence of lymph-node metastasis. This patient underwent toe amputation and has done well for 2.5 years with no evidence of recurrence. We discuss this case of subungual SCC of the toe along with others in the literature to propose an optimal standardized approach for therapy and follow-up. In so doing, we aim to advance medical knowledge of subungual SCC and to improve patient care.

A novel dendritic cell-based cancer vaccine produces promising results in a syngenic CC-36 murine colon adenocarcinoma model.

BACKGROUND: This study was conducted to test the efficacy of a new cancer vaccine, composed of dendritic cells (DCs) pulsed with an interleukin-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) in a CC-36 murine colon adenocarcinoma model. MATERIALS AND METHODS: CC-36 tumor cells were injected subcutaneously into the left flank of four- to six-week old male BALB/c mice. The mice were divided into three groups, each of which received one of the following treatments: (1) DCs pulsed with the IL-2 gene-encoded vaccinia oncolysate (DC-IL-2VCO), (2) DCs pulsed with the tumor oncolysate alone (DC-CO), or (3) no treatment (control). Tumor incidence was measured, and survival rates were compared using a paired Student's t-test. Cytolytic T cell activity was measured in peripheral blood lymphocytes (PBL) and splenic lymphocytes using a (51)Cr-release assay. Lastly, mice were depleted of either CD4+ or CD8+ lymphocytes prior to receiving the vaccine to test the mechanism of tumor immunity in these mice. RESULTS: Mice treated with DC-IL-2VCO demonstrated decreased tumor burden, increased survival, and greater cytolytic activity compared with control mice and mice receiving DC-CO. In addition, mice depleted of CD8+ T cells prior to immunization with IL-2VV + DC-IL-2VCO had a significant increase in the incidence of tumor, similar to the untreated control mice. CONCLUSIONS: DCs pulsed with an IL-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) produced safe and effective immune responses in a murine CC-36 colon adenocarcinoma model. This vaccine (DC-MelVac; Patent no. 11221/5) has the potential to treat humans with cancer, and has received FDA approval for use in Phase I clinical trials.