Impact of autotransfusion on recurrence of colorectal cancer liver metastasis: Long-term follow-up of patients undergoing curative intent hepatectomy.

INTRODUCTION: Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS: Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS: Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively.  Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION: Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.

Outcomes of robotic lobectomy for non-small cell lung cancer in a National Cancer Institute-Comprehensive Cancer Center vs. National Cancer Database.

Background: There continues to be a rise in the proportion of resectable non-small cell lung cancer (NSCLC) with the recent expansion of criteria for low-dose lung cancer screening. These are increasingly being treated with minimally invasive techniques. Our study aims to compare outcomes of robotic lobectomy (RL) for NSCLC at a National Cancer Institute-designated Comprehensive Cancer Center (NCI-CCC) to those of open lobectomy (OL), video-assisted thoracoscopic lobectomy (VL), or RL as reported in the National Cancer Database (NCDB). Methods: The first 1,021 patients with NSCLC who underwent RL between 2010 and 2020 were matched with peers from the NCDB who had OL, VL, or RL. Matching was performed based on a propensity score calculated by logistic regression using multiple variables. Surgical outcomes included numbers of examined lymph nodes, performance of mediastinal lymphadenectomy, length of stay (LOS), and 30-day mortality. Kaplan-Meier curves and overall survival (OS) were analyzed using log-rank tests. Results: Most common postoperative complications were persistent air leak, atrial fibrillation, and pneumonia. Median LOS was 4 days, and the 30-day mortality rate was 1% (n=10/1,021). Compared to NCDB patients who underwent OL, NCI-CCC patients had a higher mean number of retrieved lymph nodes (P=0.001), higher rate of mediastinal lymphadenectomy (P<0.001), and shorter median LOS (4 vs. 6 days; P<0.001). There was no difference in 30-day mortality (P=0.176). Kaplan-Meier analyses showed no differences in median OS (log-rank P=0.953) or 5-year OS (P=0.774). Compared to NCDB VL, NCI-CCC patients had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 13.8%, P<0.001). There were no differences in 30-day mortality (P=0.379) or in median LOS (P=0.351). Kaplan-Meier analyses showed no differences in median OS (P=0.720) or 5-year OS (P=0.735). NCI-CCC patients were also matched with NCDB RL patients and had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 9.5%; P <0.001). There were no differences in 30-day mortality (P=0.899) or in median LOS (P=0.252). Kaplan-Meier analyses showed no differences in median OS (P=0.484) or 5-year OS (P=0.524). Conclusions: RL for NSCLC performed in an NCI-CCC appears to have improved perioperative outcomes with comparable long-term OS compared to national benchmarks in OL and VL.

Impact of Enhanced Recovery After Surgery on Postoperative Outcomes for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been associated with significant morbidity and increased hospital length of stay (LOS). The authors report their experience after implementation of an enhanced recovery after surgery (ERAS) program for CRS-HIPEC. METHODS: Outcomes were analyzed before and after ERAS implementation. The components of ERAS included preoperative carbohydrate loading, goal-directed fluid management, multimodal pain management, minimization of narcotic use, avoidance of nasogastric tubes, and early mobilization and feeding. RESULTS: Of 168 procedures, 88 (52%) were in the pre-ERAS group and 80 (48%) were in the post-ERAS group. The two groups did not differ in terms of age, sex, comorbidities, peritoneal carcinomatosis index scores, completeness of cytoreduction, or operative time. The ERAS patients received fewer fluids intraoperatively (mean, 4.2 vs 6.4 L; p < 0.01). The mean LOS was 7.9 days post-ERAS compared with 10.0 days pre-ERAS (p = 0.015). Clavien-Dindo complications classified as grade ≥ 3 were lower after ERAS (23.7% vs 38.6%; p = 0.04). Moreover, the readmission rates remained the same (16.2% vs 13.6%; p = 0.635). CONCLUSIONS: Implementation of an ERAS program for patients undergoing CRS-HIPEC is feasible and not associated with an increase in overall major complications or readmissions. These data support incorporation of ERAS protocols for CRS-HIPEC procedures.

Feasibility of hand-assisted laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancy.

BACKGROUND: In light of the modern surgical trend towards minimally invasive surgery, we aim to assess the feasibility of hand-assisted laparoscopic (HAL) cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal surface malignancy (PSM). METHODS: Patients with PSM secondary to colorectal cancer or pseudomyxoma peritonei with peritoneal cancer index (PCI) of ≤ 10 were considered for HAL CRS and HIPEC. One patient had PCI of 15 but based on the disease distribution laparoscopic-assisted CRS and HIPEC was thought to be feasible, thus was also included. These patients were compared to matched controls who underwent open CRS and HIPEC for similar pathologies. Matching was performed on age and PCI to reflect a comparable complexity of the operation, and tumor grade for comparable risk of disease recurrence. RESULTS: Eleven patients were included in each group. In both groups, mean PCI was 4.1, mean age was 58.5 years, and 81.8% were well-moderately differentiated tumors. Complete cytoreduction was achieved in all patients. Upon comparison, HAL patients had significantly less blood loss and 3-day shorter hospitalization. No difference was demonstrated in operative time, number of visceral resections, and rate of omentectomy/peritonectomy. Also, no difference was detected in morbidities and 30-day readmission rates. No intraperitoneal recurrences have been reported in the HAL group after a median follow-up of 11 months. CONCLUSION: HAL CRS and HIPEC is a feasible procedure and can be considered for PSM with low PCI. It offers very acceptable and comparable short-term outcomes to the conventional open approach.

Knowledge, attitudes and practice of surgeons regarding nutritional support in CRS and HIPEC patients: Are we missing something?

Nutrition's impact on the surgical outcome has been established in various surgical specialties. However, data addressing the nutritional aspect following surgery for peritoneal surface malignancies are considered scarce. We aim to evaluate the knowledge, attitudes, and practice of surgeons regarding their nutritional support for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) via a survey directed to self-evaluate nutritional knowledge, screening, and practice toward patients. The survey was submitted to the attendees of the International Regional Cancer Therapies Symposium. The response rate was 37% (56/151). Most surgeons estimated their knowledge and malnutrition screening skills in CRS and HIPEC to be 'adequate' or better. Only 35.19% reported the availability of nutritional screening and assessment tools for CRS and HIPEC patients. 86.5% of participants stated that their CRS and HIPEC patients have access to a dietitian on inpatient and outpatient basis. However, only 32.69% reported to 'always' consult a dietitian. Otherwise, the involvement of a nutrition specialist is considered on variable basis. Despite the consensus on the importance of nutrition in HIPEC patients, there appears to be a profound underutilization of nutrition specialists in the patients' management, which may have had in impact on their surgical outcome.

Transient Exocrine Pancreatic Insufficiency: First Report of an Unrecognized Complication of Cytoreductive Surgery and HIPEC.

BACKGROUND: As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine pancreatic insufficiency (EPI) following CRS and HIPEC. PATIENTS AND METHODS: Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in all patients in the immediate postoperative period. Patients with diarrhea who had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and their symptomatic progression was followed. RESULTS: A total of 26 patients were included. Eleven patients (42.31%) developed postoperative refractory diarrhea, nine of whom had a low FE1 level. These patients were treated with PERT either directly or after completion of antibiotics course if C. difficile toxin was positive. Eight patients demonstrated symptomatic resolution of their diarrhea, and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea had lower FE1 levels, and were more likely to have had a terminal ileum resection and had a longer hospital stay. Regression analysis identified the rapid rise of a patient's core temperature by >1°C within 15 minutes as the sole predictor of EPI occurrence. CONCLUSION: EPI is a potential adverse event following CRS and HIPEC and might be largely responsible for refractory diarrhea. In our patients with refractory diarrhea and low FE1, PERT provided immediate symptomatic relief. The biological basis of this phenomenon remains unclear and warrants further investigation.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Elderly Patients: Complete Cytoreduction Is Feasible and Crucial for Improved Survival Despite High Carcinomatosis Index.

BACKGROUND: We aimed to study the surgical outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients, and investigate whether the pursuit of complete cytoreduction implies a survival benefit despite a high peritoneal carcinomatosis index (PCI). PATIENTS AND METHODS: All CRS and HIPEC procedures performed for patients with peritoneal surface malignancy (PSM) ≥65 years old between 2005-2017 were included. A control group comprising patients 60-64 years old who underwent CRS and HIPEC over the same period was also selected for comparison of characteristics and outcomes. RESULTS: A total of 54 elderly patients and 27 control patients were included. Increasing age did not result in any difference in demographics, perioperative characteristics, or surgical outcomes. Elderly patients who achieved completeness of cytoreduction (CC) 0/1 were compared to those with CC2/3, and were found to have a higher body mass index, lower peritoneal cancer index, higher rate of inpatient mortality, and a significantly longer median survival (43 vs. 15 months; p=0.020). Cox multivariate regression identified Charlson score ≥2, the occurrence of major morbidities, colorectal and sarcoma primary tumor, and CC2/3 as significant predictors of poor survival. CONCLUSION: CRS and HIPEC are feasible in elderly patients without a significant effect of increasing age on the surgical outcomes. CC0/1 carries higher postoperative mortality rate, but yields a longer overall survival. Baseline comorbidities, postoperative complications, certain histologies, and CC2/3 are predictors of poor prognosis in this population. PCI is a predictor of CC, but not of survival when CC0/1 is achieved.

Evaluation of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a community setting: A cost-utility analysis of a hospital's initial experience and reflections on the health care system.

BACKGROUND: The combination of Cytoreductive Surgery (CRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has been gaining a considerable interest by surgeons throughout the United States due to the significant survival improvement it provides for peritoneal surface malignancies and the ability to reproduce comparable clinical results in numerous health care centers. However, CRS plus HIPEC has not been sufficiently investigated from the economic standpoint in the United States where a wide variety of health care insurers exists. This study was conducted to analyze hospital/surgeon cost and reimbursement data at a community hospital offering a new peritoneal surface malignancy program, and expand the discussion to analyze future healthcare implementation on this procedure in the United States. METHODS: This is a retrospective economic analysis of an initial CRS plus HIPEC experience at a community non-teaching medical center. This study was conducted using hospital/surgeon cost and reimbursement based on the Office of Finance data at Edward Hospital Cancer Center (Naperville, IL). All patients who underwent CRS and HIPEC between June 2013 and August 2014 were included in this analysis. We aimed to assess CRS plus HIPEC purely from the financial perspective on the initial admission regardless of the patients' advancement of the disease or postoperative adverse events. RESULTS: Twenty-five patients underwent 26 CRS plus HIPEC procedures. Twelve patients had private insurance plans (PRV) whereas 13 were covered by public insurers (PUB). Median overall length of stay (LOS) was 10 days (PRV 10 days vs. PUB 11 days; P = 0.76.) Average hospital cost was $38,369 (PRV $37,093 vs. PUB $39,463; P = 0.67), and average reimbursement for our patient population was $45,243 (PRV $48,954 vs. PUB $42,062; P = 0.53). It was noted that CRS plus HIPEC generated more net profit in patients with private insurance than in those with public plans, however, not statistically significant ($11,861 vs. $2,599 per patient, respectively; P = 0.38). Evaluating surgeon's data, average surgeon's charge was $29,139 (PRV $28,440 vs. PUB $29,737; P = 0.80), and average patients' payment was $8,126 (PRV 9,234 vs. PUB 7,176; P = 0.47). CONCLUSION: CRS plus HIPEC is profitable in the community setting for both the hospital and surgeon. Both private and public insurers reimbursed profitably, though with a greater profit margin from private insurers. As CRS plus HIPEC is becoming more widely recognized as a standard of care for patients with peritoneal surface malignancy, it is increasingly important to understand and report its associated costs and variability in insurance coverage, especially in light of the current healthcare structure changes in the United States. It is strongly encouraged to report and present a wider scope of CRS plus HIPEC economic experiences in a variety of hospital settings to provide further evidence for future healthcare implementations in the United States. J. Surg. Oncol. 2016;113:544-547. © 2016 Wiley Periodicals, Inc.