Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

Actual 5-Year Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis of Colorectal Origin.

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. METHODS: We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. RESULTS: A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. CONCLUSIONS: Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Surgical management of pancreatic ductal adenocarcinoma: a narrative review.

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death in the United States and is projected to become the second-leading cause of cancer-related death by 2030. Despite advances in systemic and radiation therapy, for patients with surgically resectable PDAC, complete surgical resection is the only potentially curative treatment option. The conduct of a safe, technically excellent pancreatectomy is essential to achieve optimal perioperative outcomes and long-term survival. In this narrative review, evidence from large, well-executed studies and clinical trials examining the technical aspects of pancreatectomy is reviewed. Methods: A search was conducted in PubMed, Medline, and Cochrane Review databases to identify English-language randomized clinical trials, meta-analyses, and systematic reviews assessing surgical aspects of pancreatectomy for PDAC published between 2010 to 2023. Key Content and Findings: We identified retrospective and prospective studies evaluating the technical aspects of surgery for PDAC. In this review, we evaluate data on surgical techniques of pancreatectomy for PDAC, including the role of minimally invasive techniques, extent of lymphadenectomy, reconstruction options after pancreatoduodenectomy, and the role of surgical drainage. Conclusions: Surgical resection has a critical role in the treatment of operable PDAC. While pancreatic cancer surgery is an active area of research, conducting a technically excellent surgical resection maintains paramount importance for both oncological and perioperative outcomes. In this review, we summarize the latest evidence on surgical technique for operable PDAC.

Implementing the first program of minimally invasive esophagectomy for cancer in Israel: shifting the paradigm in a high-volume center - a cohort study.

BACKGROUND: Esophagectomy is associated with significant perioperative morbidity. Limited data are available on the process of implementation of minimally invasive techniques in esophagectomy and related outcomes. The authors sought to describe implementation processes and outcomes following the implementation of the first minimally invasive esophagectomy (MIE) program at a high-volume center in Israel under the mentorship of American early adopters. METHODS: Patients who underwent esophagectomy for esophageal carcinoma 2011-2022 were included. Early and late cohorts were created for learning curve analysis. Secondary analysis included patients who underwent open esophagectomy 1997-2011. RESULTS: Overall, 300 patients underwent MIE: three-field MIE (3F-MIE) was performed in 242 (80.7%) patients, two-field MIE (2F-MIE) in 58 (19.3%) patients. Following program implementation in 2012, the number of MIE performed increased during the first 3 years ( n =33, 86.8% in 2015). Among 3F-MIE patients, a higher number of retrieved lymph nodes was reported during later cases (median, IQR1-3 17, 12-23 vs. 12, 8-12, P <0.001) while surgeries required a longer time (median, IQR1-3 300 min, 261-355 vs. 262.5, 239-300, P <0.001). Among 2F-MIE patients, the late cohort had lower rates of prolonged ICU admissions than earlier counterparts ( n =2, 6.9% vs. n =9, 31%, P =0.041), overall and severe 30-day complications ( n =12, 41.4% vs. n =23, 79.3%, P <0.001 and n =7, 24.1% vs. n =23, 79.3%, P =0.003). CONCLUSIONS: MIE was safely implemented. Nodal yield was higher among MIE patients than open esophagectomy. During the study years, open approach was gradually abandoned in favor of 3F-MIE procedures, while 2F-MIE increased over the course of the last years.

The role of physical status versus mental status in predicting the quality of life of patients with lumbar disk herniation.

PURPOSE: To explore the role of physical status versus mental status in predicting the quality of life (QOL) of patients with lumbar disk herniation (LDH). METHOD: In this correlative study 51 patients with LDH were recruited in their conservative stage of treatment. After profiling their physical status, all participants reported about pain level (according to VAS), pain perception using the Pain Catastrophizing Scale (PCS), and disability level (according to Oswestry Low Back Pain Disability Questionnaire). Their mental status was evaluated using the Spielberger's State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI-II). Their QOL was evaluated by the World Health Organization Quality of Life Questionnaire, brief version (WHOQOL-BREF). RESULTS: Physical status/disability level correlated with anxiety and depression. While Physical status predicted physical QOL, mental status, and mainly anxiety and depression were the significant predictors of psychological, social, and environmental QOL. CONCLUSIONS: Mental status may play a significant role in reducing most QOL domains among patients with LDH. The evaluation and intervention process should consider both physical and mental status and their relation to the person's QOL. Since QOL is a major parameter in determining intervention type and success this elaborated perspective may contribute to the intervention planning and outcomes. Implications for rehabilitaion A significant mental distress may accompany the physical disability of patients with LDH. The role of this mental distress in reducing the QOL of patients with LDH may be greater than that of their physical disability. The evaluation and intervention for patients with LDH should refer to both physical and mental status and explore their impacts on quality of life in order to elevate intervention success.