Immediate Adjuvant Chemotherapy in Non-Metastatic Colon Cancer: Phase I Trial Evaluating a Novel Treatment Protocol.

BACKGROUND: The optimal timing of adjuvant chemotherapy (AC) in non-metastatic colon cancer is poorly defined. Delays in AC result in decreased survival. Effective cytotoxic treatments should be considered during the perioperative phase of care. The immediate adjuvant chemotherapy (IAC) concept intends to capitalize on the therapeutic benefits that can be achieved in the perioperative period. We aim to demonstrate that IAC is safe and tolerable. PATIENT AND METHODS: Microsatellite stable invasive adenocarcinomas were treated with intravenous Leucovorin 20 mg/m2 and single dose of 5-Flurouracil 400mg/m2 at the time of surgery. High-risk stage II and stage III received the first dose of standard AC at 14 days after surgery. Serial measurements of blood-based biomarkers were measured. Quality of life (QOL) was measured using EORTC QLQ-C30. RESULTS: Of the 20 patients recruited, 40% had final pathology of stage III, 40% stage II and 20% stage I. All patients received intra-operative chemotherapy with no associated morbidity. Median length of stay was 2 days (range of 2-4). There was no intraoperative morbidity with 5% (N = 1) grade 3 complication. AC was administered to 65% of patients. The median time to AC was 14 days (range 14-36). Overall quality of life and health scores were similar before surgery and at 30-day postoperatively (P < .05). CONCLUSIONS: A protocol based on IAC starting at the time of surgical resection was found to be safe and feasible with no adverse effects on surgical morbidity or quality of life. Further prospective studies are needed to explore the oncologic benefit of this novel systemic treatment approach.

Readmission and complications after robotic surgery: experience of 10,000 operations at a comprehensive cancer center.

Evaluation of safety is of paramount importance with adoption of novel surgical technology. Although robotic surgery has become widely used in oncologic surgery, analysis of safety is lacking in comparison to traditional techniques. Standardized assessment of robotic surgical outcomes and adverse events following oncologic surgery is necessary for quality improvement with innovative technology. Between 2003 and 2016, 10,013 unique robotic operations were performed in 9,858 patients. Our prospectively maintained database was retrospectively reviewed for hospital readmissions and Clavien-Dindo grade ≥ 2 complications within 30 days. Multivariable logistic regression was used to identify predictors of surgical complications and hospital readmissions. Cases were stratified by discipline: genitourinary (n = 8240), gynecologic (n = 857), thoracic (n = 457), gastrointestinal (n = 322), hepatobiliary (n = 60), ear/nose/throat (n = 44) and general (n = 33). Intraoperative complications occurred in 42 surgeries (0.4%). Postoperative complications occurred in 946 patients [9.4%, highest grade 2 (n = 574), 3 (n = 288), 4 (n = 72), 5 (n = 10)]. Most frequent complications were ileus (154, 16.3%), anemia (91, 9.6%), cardiac arrhythmia (62, 6.6%), deep vein thrombosis/pulmonary embolus (47, 5.0%), wound infection (45, 4.8%) and urinary leak (43, 4.5%). 405 patients (4.0%) required readmission. Most common causes for hospital readmission were ileus (44, 10.9%), urinary leak (23, 5.7%), urinary tract infection (23, 5.7%), intra-abdominal abscess/fluid collection (23, 5.7%), and small bowel obstruction (19, 4.7%). On multivariable analysis, longer operative time and older age predicted complications and readmissions (p ≤ 0.02). Robotic-assisted surgery appears a safe for oncologic surgery with acceptable hospital readmission and complication rates. Older age and longer operative time were associated with complications and readmission.

Evaluation of Pelvic Anastomosis by Endoscopic and Contrast Studies Prior to Ileostomy Closure: Are Both Necessary? A Single Institution Review.

Contrast enema is the gold standard technique for evaluating a pelvic anastomosis (PA) prior to ileostomy closure. With the increasing use of flexible endoscopic modalities, the need for contrast studies may be unnecessary. The objective of this study is to compare flexible endoscopy and contrast studies for anastomotic inspection prior to defunctioning stoma reversal. Patients with a protected PA undergoing ileostomy closure between July 2014 and June 2019 at our institution were retrospectively identified. Demographics and clinical outcomes in patients undergoing preoperative evaluation with endoscopic and/or contrast studies were analyzed. We identified 207 patients undergoing ileostomy closure. According to surgeon's preference, 91 patients underwent only flexible endoscopy (FE) and 100 patients underwent both endoscopic and contrast evaluation (FE + CE) prior to reversal. There was no significant difference in pelvic anastomotic leak (2.2% vs. 1%), anastomotic stricture (1.1% vs. 6%), pelvic abscess (2.2% vs. 3.0%), or postoperative anastomotic complications (4.4% vs. 9%) between groups FE and FE + CE (P > .05). Flexible endoscopy alone appears to be an acceptable technique for anastomotic evaluation prior to ileostomy closure. Further studies are needed to determine the effectiveness of different diagnostic modalities for pelvic anastomotic inspection.

Evaluation of Cell-detaching Effect of EDTA in Combination with Oxaliplatin for a Possible Application in HIPEC After Cytoreductive Surgery: A Preliminary in-vitro Study.

BACKGROUND: Ethylenediaminetetraacetic acid (EDTA), a commonly used compound in laboratory medicine, is known for its membrane-destabilization capacity and cell-detaching effect. This preliminary study aims to assess the potential of EDTA in removing residual tumor cell clusters. Using an in-vitro model, this effect is then compared to the cytotoxic effect of oxaliplatin which is routinely administered during HIPEC procedures. The overall cell toxicity and cell detaching effects of EDTA are compared to those of Oxaliplatin and the additive effect is quantified. METHODS: HT-29 (ATCC® HTB-38™) cells were treated with A) EDTA only B) Oxaliplatin only and C) both agents using an in-vitro model. Cytotoxicity and cell detachment following EDTA application were measured via colorimetric MTS assay. Additionally, detached cell groups were visualized using light microscopy and further analyzed by means of electron microscopy. RESULTS: When solely applied, EDTA does not exhibit any cell toxicity nor does it add any toxicity to oxaliplatin. However, EDTA enhances the detachment of adherent colon carcinoma cells by removing up to 65% (p<0.05) of the total initial cell amount. In comparison, the sole application of highly concentrated oxaliplatin induced cell mortality by up to 66% (p<0.05). While detached cells showed no mortality after EDTA treatment, cell clusters exhibited a decreased amount of extracellular and adhesive matrix in-between cells. When combined, Oxaliplatin and EDTA display a significant additive effect with only 30% (mean p <0.01) of residual vitality detected in the initial well. EDTA and Oxaliplatin remove up to 81% (p <0.01) of adhesive HT-29 cells from the surface either by cytotoxic effects or cell detachment. CONCLUSION: Our data support EDTA's potential to remove microscopical tumor cell clusters from the peritoneum and possibly act as a supplementary agent in HIPEC procedures with chemotherapy. While adding EDTA to HIPEC procedures may significantly decrease the risk of PM recurrence, further in-vivo and clinical trials are required to evaluate this effect.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

The Utility of Diagnostic Laparoscopy in Patients Being Evaluated for Cytoreductive Surgery and Hyperthermic Peritoneal Chemotherapy.

BACKGROUND: To assess the role of diagnostic laparoscopy (DL) to evaluate candidates for optimal cytoreduction surgery of peritoneal carcinomatosis (PC) combined with hyperthermic intraperitoneal chemotherapy in a consecutive series. METHODS: The characteristics of 31 patients undergoing DL between August 2012 and October 2016 for a diagnosis of PC secondary to digestive neoplasms were retrospectively reviewed. RESULTS: Laparoscopic evaluation was successful and well-tolerated in 100% patients (N=31). In 17 patients (54.8%) the PC was deemed unresectable. A cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy was performed in 10 of 12 patients with PC considered resectable at laparoscopy wity a positive predictive value of 83.3%. One patient was diagnosed with more extensive disease than that as assessed by the DL at the time of laparotomy and 1 patient elected not to have further surgery. There were no port-site recurrences and morbidity at mean follow-up of 19.3 months. CONCLUSIONS: Laparoscopic assessment of PC is a useful tool to assess the complete resectability of peritoneal surface disease in patients for whom there is inadequate information concerning disease extent. DL also helps selected patients to avoid an unnecessary laparotomy.

Is Fecal Diversion Needed in Pelvic Anastomoses During Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

BACKGROUND: The role of fecal diversion with pelvic anastomosis during cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is not well defined. METHODS: A retrospective review of patients who underwent CRS and HIPEC between 2009 and 2016 was performed to identify those with a pelvic anastomosis (colorectal, ileorectal, or coloanal anastomosis). RESULTS: The study identified 73 patients who underwent CRS and HIPEC at three different institutions between July 2009 and June of 2016. Of these patients, 32 (44%) underwent a primary anastomosis with a diverting ileostomy, whereas 41 (56%) underwent a primary anastomosis without fecal diversion. The anastomotic leak rate for the no-diversion group was 22% compared with 0% for the group with a diverting ileostomy (p < 0.01). The 90-day mortality rate for the no-diversion group was 7.1%. The hospital stay was 14.1 ± 8.0 days in the diversion group compared with 17.9 ± 12.5 days in the no-diversion group (p = 0.12). Of those patients with a diverting ileostomy, 68% (n = 22) had their bowel continuity restored, 18% of which required a laparotomy for reversal. Postoperative complications occurred for 50% of those who required a laparotomy and for 44% of those who did not require a laparotomy (p = 0.84). CONCLUSION: Diverting ileostomies in patients with a pelvic anastomosis undergoing CRS and HIPEC are associated with a significantly reduced anastomotic leak rate. Reversal of the diverting ileostomy in this patient population required a laparotomy in 18% of the cases and had an associated morbidity rate of 50%.

Contemporary management of anastomotic leak after colon surgery: assessing the need for reoperation.

BACKGROUND: We sought to investigate contemporary management of anastomosis leakage (AL) after colonic anastomosis. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database 2012 to 2013 was used to identify patients with AL. Multivariate regression analysis was performed to find predictors of the need for surgical intervention in management of AL. RESULTS: A total of 32,280 patients underwent colon resection surgery with 1,240 (3.8%) developing AL. Overall, 43.9% of patients with AL did not require reoperation. Colorectal anastomosis had significantly higher risk of AL compared with ileocolonic anastomosis (adjusted odds ratio [AOR], 1.20; P = .04). However, the rate of need for reoperation was higher for AL in colocolonic anastomosis compared with ileocolonic anastomosis (AOR, 1.48; P = .04). White blood cell count (AOR, 1.07; P < .01), the presence of intra-abdominal infection with leakage (AOR, 1.47; P = .01), and protective stoma (AOR, .43, P = .02) were associated with reoperation after AL. CONCLUSIONS: Nonoperative treatment is possible in almost half of the patients with colonic AL. The anatomic location of the anastomosis impacts the risk of AL. Severity of leakage, the presence of a stoma, and general condition of patients determine the need for reoperation.

Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the american college of surgeons national surgical quality improvement program.

IMPORTANCE: Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery have been shown to benefit selected patients with peritoneal carcinomatosis. However, these procedures are associated with high morbidity and mortality. Available data investigating the outcomes of HIPEC are mostly limited to single-center studies. To date, there have been few large-scale studies investigating the postoperative outcomes of HIPEC. OBJECTIVE: To determine the associated 30-day morbidity and mortality of cytoreductive surgery-HIPEC in the treatment of metastatic and primary peritoneal cancer in American College of Surgeons National Surgical Quality Improvement Program centers. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of HIPEC cases performed for primary and metastatic peritoneal cancer diagnoses was conducted. The cytoreductive surgical procedures were sampled, and disease processes were identified. Patient demographics, intraoperative occurrences, and postoperative complications were reviewed from the American College of Surgeons National Surgical Quality Improvement Program from 2005-2011. MAIN OUTCOMES AND MEASURES: Thirty-day mortality and morbidity. RESULTS: Of the cancers identified among the 694 sampled cases, 14% of patients had appendiceal cancer, 11% had primary peritoneal cancer, and 8% had colorectal cancer. The American Society of Anesthesiologists classification was 3 for 70% of patients. The average operative time was 7.6 hours, with 15% of patients requiring intraoperative transfusions. Postoperative bleeding (17%), septic shock (16%), pulmonary complications (15%), and organ-space infections (9%) were the most prevalent postoperative complications. The average length of stay was 13 days, with a 30-day readmission rate of 11%. The rate of reoperation was 10%, with an overall mortality rate of 2%. CONCLUSIONS AND RELEVANCE: American College of Surgeons National Surgical Quality Improvement Program hospitals performing HIPEC have acceptable rates of morbidity and mortality.