Background Surgical site infections (SSIs) remain a major source of morbidity and cost after resection of intra-abdominal malignancies. Negative-pressure wound therapy (NPWT) has been reported to ...significantly reduce SSIs when applied to the closed laparotomy incision. This article reports the results of a randomized clinical trial examining the effect of NPWT on SSI rates in surgical oncology patients with increased risk for infectious complications. Study Design From 2012 to 2016, two hundred and sixty-five patients who underwent open resection of intra-abdominal neoplasms were stratified into 3 groups: gastrointestinal (n = 57), pancreas (n = 73), or peritoneal surface (n = 135) malignancy. They were randomized to receive NPWT or standard surgical dressing (SSD) applied to the incision from postoperative days 1 through 4. Primary outcomes of combined incisional (superficial and deep) SSI rates were assessed up to 30 days after surgery. Results There were no significant differences in superficial SSIs (12.8% vs 12.9%; p > 0.99) or deep SSI (3.0% vs 3.0%; p > 0.99) rates between the SSD and NPWT groups, respectively. When stratified by type of surgery, there were still no differences in combined incisional SSI rates for gastrointestinal (25% vs 24%; p > 0.99), pancreas (22% vs 22%; p > 0.99), and peritoneal surface malignancy (9% vs 9%; p > 0.99) patients. When performing univariate and multivariate logistic regression analysis of demographic and operative factors for the development of combined incisional SSI, the only independent predictors were preoperative albumin (p = 0.0031) and type of operation (p = 0.018). Conclusions Use of NPWT did not significantly reduce incisional SSI rates in patients having open resection of gastrointestinal, pancreatic, or peritoneal surface malignancies. Based on these results, at this time NPWT cannot be recommended as a therapeutic intervention to decrease infectious complications in these patient populations.
Background
Pancreatic cancer is a disease of older adults, who may present with limited physiologic reserve. The authors hypothesized that a frailty index can predict postoperative outcomes after ...pancreaticoduodenectomy (PD).
Methods
All patients who underwent PD were identified in the 2005–2012 NSQIP Participant Use File. Patients undergoing emergency procedures, those with an American Society of Anesthesiologists (ASA) classification of five, and those with a diagnosis of preoperative sepsis were excluded from the study. A modified frailty index (mFI) was defined by 11 variables within the National Surgical Quality Improvement Program (NSQIP) previously used for the Canadian Study of Health and Aging-Frailty Index. An mFI score of 0.27 or higher was defined as a high mFI. Uni- and multivariate analyses were performed to evaluate postoperative outcomes.
Results
This study enrolled 9986 patients (age 65 ± 12 years, 48.8% female) who underwent PD. Of these patients, 6.4% (
n
= 637) had a high mFI (>0.27). Increasing mFI was associated with higher prevalence of postoperative morbidity (
p
< 0.001) and 30-days mortality (
p
< 0.001). In the univariate analysis, high mFI was associated with increased morbidity (odds ratio OR 1.68; 95% confidence interval CI 1.43–1.97;
p
< 0.001) and 30-days mortality (OR 2.45; 95% CI 1.74–3.45;
p
< 0.001). After adjustment for age, sex, ASA classification, albumin level, and body mass index (BMI), high mFI remained an independent preoperative predictor of postoperative morbidity (OR 1.544; 95% CI 1.289–1.850;
p
< 0.0001) and 30-days mortality (OR 1.536; 95% CI 1.049–2.248;
p
= 0.027).
Conclusions
High mFI is associated with postoperative morbidity and mortality after PD and can aid in preoperative risk stratification.
Background Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy ...and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. Results Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). Conclusions This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.
Background
Chemotherapy dosing duration and perfusion temperature vary significantly in HIPEC protocols. This study investigates patient-derived tumor organoids as a platform to identify the most ...efficacious perfusion protocol in a personalized approach.
Patients and Methods
Peritoneal tumor tissue from 15 appendiceal and 8 colon cancer patients who underwent CRS/HIPEC were used for personalized organoid development. Organoids were perfused in parallel at 37 and 42 °C with low- and high-dose oxaliplatin (200 mg/m
2
over 2 h vs. 460 mg/m
2
over 30 min) and MMC (40 mg/3L over 2 h). Viability assays were performed and pooled for statistical analysis.
Results
An adequate organoid number was generated for 75% (6/8) of colon and 73% (11/15) of appendiceal patients. All 42 °C treatments displayed lower viability than 37 °C treatments. On pooled analysis, MMC and 200 mg/m
2
oxaliplatin displayed no treatment difference for either appendiceal or colon organoids (19% vs. 25%,
p
= 0.22 and 27% vs. 31%,
p
= 0.55, respectively), whereas heated MMC was superior to 460 mg/m
2
oxaliplatin in both primaries (19% vs. 54%,
p
< 0.001 and 27% vs. 53%,
p
= 0.002, respectively). In both appendiceal and colon tumor organoids, heated 200 mg/m
2
oxaliplatin displayed increased cytotoxicity as compared with 460 mg/m
2
oxaliplatin (25% vs. 54%,
p
< 0.001 and 31% vs. 53%,
p
= 0.008, respectively).
Conclusions
Organoids treated with MMC or 200 mg/m
2
heated oxaliplatin for 2 h displayed increased susceptibility in comparison with 30-min 460 mg/m
2
oxaliplatin. Optimal perfusion protocol varies among patients, and organoid technology may offer a platform for tailoring HIPEC conditions to the individual patient level.
Immunotherapy efficacy data on appendiceal cancer from clinical trials does not exist, due to appendiceal cancer incidence of 0.97 per 100,000. The goal of this study was to preclinically explore the ...application of immunotherapy in treating appendiceal cancer in a personalized organoid model.
Patient tumor organoids (PTO) were fabricated using unsorted tumor cells with and without enrichment with patient-matched immune components derived from peripheral blood leukocytes, spleen, or lymph nodes immune-enhanced PTOs (iPTO). Organoids were cultured for 7 days, followed by treatment with immunotherapy (pembrolizumab, ipilimumab, nivolumab), and assessed for treatment efficacy.
Between September 2019 and May 2021, 26 patients were enrolled in the study. Successful testing was conducted in 19 of 26 (73.1%) patients, with 13 of 19 (68.4%) and 6 of 19 (31.6%) patients having low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primaries, respectively. Immunotherapy response, with increased expression of granzyme B and cleaved caspase 3 and decreased expression of CK20 and ATP activity, was exhibited in 4 of 19 (21.1%) pembrolizumab-treated and 2 of 19 (10.5%) nivolumab-treated iPTOs. Post-immunotherapy cellular viability, in responding HGA organoids to pembrolizumab, decreased to less than 15% (
< 0.05). LGA iPTO treatment responses were observed in pembrolizumab and nivolumab, with an 8%-47.4% (
< 0.05) viability compared with controls. Ipilimumab showed no efficacy in the examined cohort.
Immunotherapy shows measurable efficacy in appendiceal cancer organoids. Information derived from immunocompetent organoids may be applied in selecting patients for clinical trial enrollment in rare diseases where preclinical models of disease are lacking.
This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM).
A ...multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival.
Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation SD, 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P < .001), absence of lymph node metastasis (P < .001), completeness of cytoreduction scores of CC-0 or CC-1 (P < .001), and HIPEC (P = .002).
The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.
Background and Objectives
Frailty disproportionately impacts older patients with gastrointestinal cancer, rendering them at increased risk for poor outcomes. A frailty index may aid in preoperative ...risk stratification. We hypothesized that high modified frailty index (mFI) scores are associated with adverse outcomes after tumor resection in older, gastrointestinal cancer patients.
Methods
Patients (60‐90 years old) who underwent gastrointestinal tumor resection were identified in the 2005‐2012 NSQIP Participant Use File. mFI was defined by 11 previously described, preoperative variables. Frailty was defined by an mFI score >0.27. The postoperative course was evaluated using univariate and multivariate analysis.
Results
41 455 patients (mean age 72.4 years, 47.4% female) were identified. The most prevalent form of cancer was colorectal (69.3%, n = 28 708) and 2.8% of patients were frail (n = 1,164). Frail patients were significantly more likely to have increased length of stay (11.7 vs 9.0 days), major complications (29.1% vs 17.9%), and 30‐day mortality (5.6% vs 2.5%), (all P < 0.001). Multivariate analysis identified mFI as an independent predictor of major complications (OR 1.52, 95%CI 1.39‐1.65, P < 0.001) and 30‐day mortality (OR 1.48, 95%CI 1.24‐1.75, P < 0.001).
Conclusions
mFI was associated with the incidence of postoperative complications and mortality in older surgical patients with gastrointestinal cancer.
Background Treatment of peritoneal metastases from appendiceal and colon cancer with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) shows great promise. Although ...long-term disease-free survival is achieved in some cases with this procedure, many patients have recurrence. Oncologists have treated such recurrences of appendiceal cancer similarly to colorectal carcinoma, which has been largely ineffective. This study uses gene expression analysis of peritoneal metastases to better understand these neoplasms. Study Design From a prospectively maintained database and tissue bank, 41 snap frozen samples of peritoneal metastases (26 appendiceal, 15 colorectal) from patients undergoing HIPEC with complete cytoreduction and more than 3 years of follow-up underwent global gene expression analysis. Distinct phenotypes were identified using unsupervised hierarchical clustering based on differential gene expression. Survival curves restratified by genotype were generated. Results Three distinct phenotypes were found, 2 consisting of predominantly low grade appendiceal samples (10 of 13 in Cluster 1 and 15 of 20 in Cluster 2) and 1 consisting of predominantly colorectal samples (7 of 8 in Cluster 3). Cluster 1 consisted of patients with good prognosis and Clusters 2 and 3 consisted of patients with poor prognosis (p = 0.006). Signatures predicted survival of low- (Cluster 1) vs high-risk (Cluster 2) appendiceal (p = 0.04) and low-risk appendiceal (Cluster 1) vs colon primary (Cluster 3) (p = 0.0002). Conclusions This study represents the first use of gene expression profiling for appendiceal cancer, and demonstrates genomic signatures quite distinct from colorectal cancer, confirming their unique biology. Consequently, therapy for appendiceal lesions extrapolated from colonic cancer regimens may be unfounded. These phenotypes may predict outcomes guiding patient management.
Abstract Background This study evaluates the efficacy of negative-pressure therapy (NPT) in preventing surgical site infections (SSIs) in high-risk surgical oncology patients. Methods A retrospective ...analysis of 191 operations for colorectal, pancreatic, or peritoneal surface malignancies was performed. Incisional NPT was used in patients with multiple SSI risk factors. Rates of SSIs were compared with patients treated with a standard sterile dressing (SSD). Results NPT was used in 104 patients, whereas SSDs were used in 87 patients. Despite being at an increased risk of SSI, patients treated with NPT developed fewer superficial incisional SSIs compared with SSD patients (6.7% vs 19.5%, P = .015). In a subgroup analysis of clean-contaminated cases, NPT was associated with fewer superficial incisional SSIs (6.0% vs 27.4%, P = .001), fewer total SSIs (16.0% vs 35.5%, P = .011), and fewer wound openings for any reason (16.0% vs 35.5%, P = .011). Conclusions Our findings suggest that NPT decreases SSIs in high-risk surgical oncology patients.
Background
This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant ...disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes.
Methods
All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS).
Results
Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3–4, intermediate: 5–7, high: 8–10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS.
Conclusions
By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.
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