Negative Pressure Wound Therapy to Reduce Surgical Site Infections after CRS/HIPEC.

BACKGROUND: Surgical site infections (SSIs) are a common cause of morbidity after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Negative pressure wound therapy (NPWT) has been proposed as a method to reduce the rates of SSIs; however, there is paucity in the literature on the efficacy in this population. The goal of this study was to determine whether routine use of NPWT in patients undergoing CRS/HIPEC could reduce the risk of developing SSI. METHODS: We performed a retrospective before-after study to assess the rates of SSI with NPWT compared with a standard postoperative surgical dressing (SSD) in all patients undergoing CRS/HIPEC from November 2013 to December 2021 at a single tertiary care center. The primary outcome was rate of SSI. A multivariate logistic regression analysis was performed to evaluate for risk factors for SSI. RESULTS: A total of 178 patients were treated with CRS/HIPEC over the study period. Seventy patients had placement of SSD, and 108 patients had placement of NPWT. Rates of SSI were 11.4% (8/70) and 5.6% (6/108) in the two groups, respectively (p = 0.16). On multivariate analysis, patients treated with NPWT had a significantly lower risk of developing an SSI (OR 0.24 [0.06, 0.92], p = 0.037). Patients living >50 km from the hospital had significantly higher risk of developing SSI (OR 2.03 [1.09, 3.78], p = 0.026). CONCLUSIONS: These results suggest that routine use of NPWT can reduce the risk of developing an SSI in patients undergoing CRS/HIPEC for peritoneal malignancy.

Factors associated with recurrent appendicitis after nonoperative management.

BACKGROUND: The objective of this study is to identify predictors for recurrent appendicitis in patients with appendicitis previously treated nonoperatively. METHODS: This is a prospective cohort study of all adult patients with appendicitis treated at a tertiary care hospital. Patient demographics, radiographic information, management, and clinical outcomes were recorded. The primary outcome was recurrent appendicitis within 6 months after discharge from the index admission. Given the competing risk of interval appendectomy, a time-to-event competing-risk analysis was performed. RESULTS: Of the 699 patients presenting with appendicitis, 74 were treated nonoperatively (35 [47%] were women; median [IQR] age, 48 [33,64] years), and 21 patients (29%) had recurrent appendicitis. On univariate and multivariate analysis, presence of an appendicolith on imaging was the only factor associated with a higher risk of recurrent appendicitis (p = 0.02). CONCLUSIONS: The presence of appendicolith was associated with an increased risk of developing recurrent appendicitis within 6 months.

Risk of lymph node metastasis in early gastric cancer for a Western population.

INTRODUCTION: Endoscopic resection (ER) of early gastric cancer (EGC) is increasingly used in Eastern countries due to their low rates of lymph node metastasis (LNM); however, there is a paucity of evidence in Western countries. We investigated LNM and its effect on overall survival (OS) in Western patients with EGC. METHODS: Patients diagnosed with T1 gastric cancer between 2000 and 2017 were retrospectively evaluated. Univariate Kaplan-Meier, multivariate logistic and Cox-regression models were used to assess the associations between clinical characteristics, LNM, and OS. RESULTS: Among 86 patients, median age was 68 years and 72% were male. Node positivity was 30%. Two percent of patients met the classical guidelines for ER and all were node-negative, while 16% met expanded criteria of which 14% were node-positive. T1b disease (odds ratio [OR] 41.2 [95% confidence interval [CI] 1.62-1048], p = 0.02) and lymphovascular/perineural invasion (OR 18.0 [95% CI 2.41-134], p = 0.01) were predictive of node positivity. The 5-year OS for node-negative and node-positive patients was 84% and 53% (p = 0.004), respectively. CONCLUSIONS: The risk of LNM in Western patients with EGC is higher; therefore, generalizability of the expanded criteria for ER should be interpreted with caution.

Intraoperative frozen section analysis of margin status as a quality indicator in gastric cancer surgery.

INTRODUCTION: Positive pathologic margins following gastric cancer (GC) resection carries a poor prognosis. We evaluated intraoperative frozen section (IFS) analysis of resection margins (RMs) as a quality indicator in GC surgery. METHODS: Patients referred to a provincial cancer agency with surgically resected non-metastatic GC between 2004 and 2012 were included. Associations between IFS analysis, other baseline characteristics, RMs, and overall survival (OS) were assessed using logistic regression, Kaplan-Meier analyses, and Cox proportional hazards modeling. RESULTS: Among 377 patients, median age was 67 years, 68% were male, and 16% had +RMs. Thirty-four percent of patients underwent IFS analysis, which protected against +RMs (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.16-0.73, p = 0.006) and improved OS (hazards ratio [HR]: 0.72, 95% CI: 0.54-0.98, p = 0.037). OS following re-resection of IFS positive patients was similar to IFS negative patients (69 vs. 54 months, p = 0.317). Stage III disease (OR: 12.8, 95% CI: 3.00-55.0, p = 0.001) and gastroesophageal junction tumors (OR: 2.25, 95% CI: 1.05-4.78, p = 0.036) predicted +RMs. Stage III disease led to worse OS (HR: 2.89, 95% CI: 1.92-4.34, p < 0.001) while intestinal histology improved OS (HR: 0.67, 95% CI: 0.50-0.90, p = 0.007). CONCLUSIONS: IFS analysis reduce +RMs and improve OS and should be incorporated in curative intent GC surgery for patients with locally advanced GC.

Lymph node mapping in gastric cancer: a pilot study in Western patients.

In East Asia, the role of lymph node (LN) mapping in assisting surgical lymphadenectomy, which is integral to the management of gastric cancer, has been explored. We sought to evaluate its safety and utility in Western patients. Thirteen patients with nonmetastatic gastric adenocarcinoma received endoscopic, peritumoural, submucosal indocyanine green fluorescence (ICG) injections before surgery, and ICG was assessed intraoperatively using a laparoscopic detection system. All patients underwent a laparoscopic subtotal gastrectomy, and 10 of them received D2 lymphadenectomies. ICG-mapped LNs fell outside the D1 distribution in all cases, outside the D1+ distribution in 54%, and within the D2 distribution in all cases. There were no ICG-related allergies, procedural complications, or perioperative deaths. We conclude that ICG LN mapping is safe and feasible in assisting LN dissections and localizing the primary tumour in Western patients. D2 dissections should be performed in patients with advanced gastric cancer, as LNs drained outside the D1/D1+ distributions in most cases.

Predictors of Small Bowel Obstruction Post-Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal malignancies carries considerable morbidity; however, the significance of postoperative small bowel obstruction (SBO) is not well defined. We aim to identify predictors for post-CRS/HIPEC SBO and their oncologic associations. METHODS: A retrospective review was conducted of all CRS/HIPEC cases performed at a surgical oncology center (2013-2018). Patient demographics, tumor characteristics, perioperative factors, and province-wide hospital readmissions were analyzed. Descriptive statistics were used for baseline characteristics, multivariate logistic regression for predictors of SBO at 1 year, and Kaplan-Meier method with log-rank test for survival analysis. RESULTS: A total of n = 97 CRS/HIPEC procedures were performed for diagnoses of low-grade appendiceal mucinous neoplasm (44%), high-grade appendiceal adenocarcinoma (8%), colorectal adenocarcinoma (34%), and mesothelioma (9%). The median peritoneal carcinomatosis index (PCI) score was 16. Cumulative incidence of post-CRS/HIPEC SBO readmission was 24% at 1 year and 38% at 2 and 3 years. Of 29 patients readmitted with SBO, 14 (48%) had more than one readmission for SBO, and nine surgeries were performed for obstruction. Multivariate regression identified significant independent predictors of SBO within 1-year post-CRS/HIPEC as high-grade appendiceal or colorectal primaries (odds ratio [OR] 4.58, p = 0.02) and PCI ≥ 20 (OR 3.27, p = 0.05). Overall survival (OS) was worse in patients readmitted with SBO within 1 year compared to those without (3-year OS 58% vs. 75%, p = 0.017). CONCLUSION: SBO is the most common readmission diagnosis post-CRS/HIPEC and is associated with worse survival. High-grade appendiceal and colorectal primary tumors and PCI ≥ 20 are predictors for SBO.

A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases.

Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine's genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.

Laparoscopic versus open resection in patients with locally advanced colon cancer.

BACKGROUND: Surgical resection of locally advanced colon cancer (LACC) is challenging due to tumor size and the frequent need for multivisceral resection. The role of laparoscopic resection in LACC is controversial. This study aims to compare outcomes for laparoscopic versus open surgery in LACC. METHODS: A population-based retrospective review was conducted of patients treated at a Provincial Cancer Center for LACC from 2005 to 2015. Patients with non-metastatic T4 colon cancers were included. Descriptive, survival, and recurrence analyses were used. RESULTS: In all, 1,328 patients were reviewed, 23% of whom had laparoscopic surgery. A greater number of T4b tumors were removed via an open approach (35.9% vs 12.7%, P < .001). Positive resection margins occurred in 7.5% of laparoscopic and 16.5% of open cases (P < .001), and multivisceral resection was required in 11.0% and 27.7% (P < .001), respectively. Median follow-up was 37 months (interquartile range [IQR] 17-64) during which 48.6% patients died and 42.1% developed recurrence: locoregional (15.0%), distant (35.3%), peritoneal (11.4%). Age, right-sided tumors, nodal status, and laparoscopic approach were independent predictors of peritoneal recurrence. Overall survival (OS) (73 vs 61 months, P = .188) and recurrence-free survival (RFS) (39 vs 31 months, P = .288) were similar with both approaches. Age, nodal, and margin status were predictive of OS and RFS. CONCLUSION: Open surgical approach is used more frequently when tumors invade adjacent organs or require multivisceral resections. When employed, laparoscopic approach had similar rates of survival and recurrence compared with open approach, but was an independent predictor of peritoneal recurrence. Careful patient selection in operative approach is suggested.

Tumour grade and primary site predict patterns of recurrence and survival in patients with resected gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: Patterns of recurrence help to inform surveillance of patients with resected gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: Patients with GEP-NETs in British Columbia, Canada (2004-2015) were reviewed. Associations between tumor characteristics, recurrence and survival were analyzed. RESULTS: Among 759 patients, 41%, 25%, and 17% had grade 1, 2, and 3 disease, respectively. 387 patients had R0/R1 resections, of which 30% recurred (median 25 months). 5-year incidence of recurrence was 22% (grade 1), 46% (grade 2), and 59% (grade 3) (p < 0.001). Grade predicted distant recurrence (Grade 2 HR 1.89, 95% CI 1.16-3.07; p = 0.011; Grade 3 HR 3.29, 95% CI 1.81-5.99; p < 0.001). Compared to small bowel NETs, pancreas NETs had less peritoneal recurrence (OR 0.15, 95% CI 0.03-0.68, p = 0.014). No patients had isolated pulmonary recurrences. CONCLUSION: Higher grade tumors and pancreatic NETs require more frequent surveillance. Evidence is limited for pulmonary surveillance.

Cost-Effectiveness Analysis of Cytoreductive Surgery and HIPEC Compared With Systemic Chemotherapy in Isolated Peritoneal Carcinomatosis From Metastatic Colorectal Cancer.

BACKGROUND: Cost-effectiveness evaluations of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from metastatic colorectal cancer (mCRC) in the United States are lacking. METHODS: The authors developed a Markov model to evaluate the cost-effectiveness of CRS/HIPEC compared with systemic chemotherapy for isolated PC from mCRC from a societal perspective in the United States. The systemic treatment regimens consisted of FOLFOX, FOLFIRI, bevacizumab, cetuximab, and pantitumumab. The model inputs including costs, probabilities, survival, progression, and utilities were taken from the literature. The cycle length for the model was 2 weeks, and the time horizon was 7 years. A discount rate of 3% was applied. The model was tested for internal and external validation, and robustness was established with univariate sensitivity and probabilistic sensitivity analyses (PSA). The primary outcomes were total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $100,000 per QALY was assumed. RESULTS: The ICER for treatment with CRS/HIPEC compared with systemic chemotherapy was $91,034 per QALY gained ($74,098 per LY gained). The univariate sensitivity analysis showed that the total costs for treatment with CRS/HIPEC had the largest effect on the calculated ICER. The CRS/HIPEC treatment was a cost-effective strategy during the majority of simulations in the PSA. The average ICER for 100,000 simulations in the PSA was $70,807 per QALY gained. The likelihood of CRS/HIPEC being a cost-effective strategy at the WTP threshold was 87%. CONCLUSIONS: The CRS/HIPEC procedure is a cost-effective treatment for isolated PC from mCRC in the United States.

The impact of advanced age on short-term outcomes following gastric cancer resection: an ACS-NSQIP analysis.

BACKGROUND: Evidence on short-term outcomes for GC resection in elderly patients is limited by small samples from single-institutions. This study sought to examine the association between advanced age and short-term outcomes of gastrectomy for gastric cancer (GC). METHODS: Using ACS-NSQIP data, patients undergoing gastrectomy for GC (2007-2013) were identified. Primary outcome was 30-day major morbidity. Outcomes were compared across age categories (<65, 65-70, 71-75, 76-80, >80 years old). Univariable and multivariable regression was used to estimate the morbidity risk associated with age. RESULTS: Of 3637 patients, 60.6% were ≥65 years old. Major morbidity increased with age, from 16.3% (<65 years old) to 21.5% (76-80 years old), and 24.1% (>80 years old) (p < 0.001), driven by higher respiratory and infectious events. Perioperative 30-day mortality increased from 1.2% (<65years old) to 6.5% (>80 years old) (p < 0.0001). After adjustments, age was independently associated with morbidity for 76-80 years of age (RR 1.31, 95% CI, 1.08-1.60) and >80 years old (RR 1.49, 95% CI, 1.23-1.81). Predicted morbidity increased by 18.6% in those 75-80 years old and 27.5% in those >80 years old (compared to <65 years old) for total gastrectomy, and by 11.6% and 17.2% for subtotal gastrectomy, for worst case scenario. Morbidity increased by 5.1% in those 75-80 years old and 7.6% in those >80 years old for total gastrectomy, and by 3.1% and 4.7% for subtotal gastrectomy, for best case scenario. CONCLUSIONS: Advanced age, defined as more than 75 years, was independently associated with increased morbidity after GC resection. The magnitude of this impact is further modulated by clinical scenarios. Increased risk in elderly GC patient should be recognized and considered in indications for resection.

Patients' perceptions of palliative surgical procedures: a qualitative analysis.

BACKGROUND: Patients with incurable malignancies can require surgical intervention. We prospectively evaluated patients treated with palliative surgery to qualitatively assess peri-operative outcomes. METHODS: Eligible patients were assessed at a tertiary care cancer center. Demographic information and peri-operative morbidity and mortality were collected. Semi-structured qualitative interviews were obtained pre-operatively and post-operatively (1 month). Qualitative evaluation was performed using content analysis and an inductive approach. RESULTS: Twenty-eight patients were approached and 20 consented to interview. Data saturation was achieved after 14 patients. Median patient age was 58% and 56% were female. Peri-operative morbidity and mortality were 44% and 22%, respectively. "No other option" was seen as a dominant pre-operative theme (14 of 18). Other pre-operative themes included a "poor understanding of prognosis and the role of surgery in overall treatment plan". Post-operative themes included a "perceived benefit from surgery" and "satisfaction with decision-making", notwithstanding significant complications. Improved understanding of prognosis and the role of surgery were described post-operatively. CONCLUSIONS: Despite limited options and a poor understanding of prognosis, many patients perceived benefit from palliative surgery. However, peri-operative mortality was substantial. A robust and thorough patient-centered discussion about individual goals for surgery should be undertaken by surgeon, patient and family prior to embarking on a palliative operation.

Results of Resection for Recurrent or Residual Retroperitoneal Sarcoma After Failed Primary Treatment.

BACKGROUND: Local recurrence after resection of retroperitoneal sarcoma (RPS) is a common and difficult problem. Gross residual disease after incomplete resection is a particular challenge. The authors reviewed their experience with patients referred for management of recurrent or residual RPS. METHODS: Patients seen at the authors' center from 1996 to 2013 who had undergone resection at an outside institution were identified from a prospective database. Kaplan-Meier survival curves were generated and compared by log-rank analysis. RESULTS: A total of 45 patients were referred with recurrent (n = 33) or residual (n = 12) disease. Before initial surgery elsewhere, cross-sectional imaging (computed tomograpy/magnetic resonance imaging) had been obtained for 30 patients (67 %) and percutaneous biopsy for 8 patients (18 %). At referral to the authors' center, 15 patients were deemed inappropriate for resection, with a subsequent median overall survival (OS) period of 15 months. At the authors' center, 30 patients (22 with recurrent and 8 with residual disease) were resected. The majority received preoperative radiation (77 %). The postoperative mortality rate was 0 % in the recurrent group and 25 % (2/8) in the residual group (p = 0.015). Among the 30 resected patients, the median and 5-year OS was 53 months (50 %), and the OS was better in the recurrent group (median, 77 months) than in the residual group (median, 41 months (p = 0.027). The median time to local re-recurrence was 49 months in the recurrent group and 35 months in the residual group (p = 0.730). CONCLUSIONS: Durable disease control and prolonged survival may be achieved for selected patients with recurrent RPS. In this study, resection after previous grossly incomplete resection was associated with high postoperative mortality and inferior OS. The benefit of extensive surgery for these patients may be limited.

Impact of Major Complications on Patients' Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for selected patients with peritoneal surface malignancies (PSM). Although it can have significant morbidity, perioperative mortality is low. Little is known about whether major complications after CRS/HIPEC have a lasting impact on patients' quality of life (QOL). METHODS: We retrospectively reviewed data from a prospectively collected database on patients treated with CRS/HIPEC for PSM (2011-2014). Patients with CRS/HIPEC and 6-month QOL evaluation were included. Major perioperative complications (Clavien-Dindo grade 3/4) were the primary independent variable. QOL was evaluated using the validated EORTC QLQ-C30 score. The primary outcome was 6-month global health score. Secondary outcomes were individual functional and symptom domains. RESULTS: Forty-two patients were analyzed. Median age was 57.5; 64 % were female. Origin of PSM was appendix (55 %), colorectal (38 %), mesothelioma (5 %), and small bowel (2 %). Fourteen patients (33 %) had major (grade 3/4) complications. Median length of stay was 16 days; patients experiencing major complications had significantly increased length of stay (35.5 vs. 13 days, p < 0.01). Major complications included intra-abdominal abscess (9.5 %), bleeding (9.5 %), symptomatic pleural effusion (7.1 %), anastomotic leaks (7.1 %), and renal failure (2.4 %). The average global health score at 6 months was 68.1. The worst-rated symptom scores at 6 months were diarrhea (39.8) and fatigue (35.4). There were no significant differences in 6-month QOL scores between patients with and without major complications, globally or in specific domains. CONCLUSIONS: Although major complications are common after CRS/HIPEC, QOL at 6 months recovers and is similar to those without major complications.

Identification of prognostic inflammatory factors in colorectal liver metastases.

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored. METHODS: In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival. RESULTS: Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1ß, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival. CONCLUSIONS: Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation.