Remote Assessment of Real-World Surgical Safety Checklist Performance Using the OR Black Box: A Multi-Institutional Evaluation.

BACKGROUND: Large-scale evaluation of surgical safety checklist performance has been limited by the need for direct observation. The operating room (OR) Black Box is a multichannel surgical data capture platform that may allow for the holistic evaluation of checklist performance at scale. STUDY DESIGN: In this retrospective cohort study, data from 7 North American academic medical centers using the OR Black Box were collected between August 2020 and January 2022. All cases captured during this period were analyzed. Measures of checklist compliance, team engagement, and quality of checklist content review were investigated. RESULTS: Data from 7,243 surgical procedures were evaluated. A time-out was performed during most surgical procedures (98.4%, n = 7,127), whereas a debrief was performed during 62.3% (n = 4,510) of procedures. The mean percentage of OR staff who paused and participated during the time-out and debrief was 75.5% (SD 25.1%) and 54.6% (SD 36.4%), respectively. A team introduction (performed 42.6% of the time) was associated with more prompts completed (31.3% vs 18.7%, p < 0.001), a higher engagement score (0.90 vs 0.86, p < 0.001), and a higher percentage of team members who ceased other activities (80.3% vs 72%, p < 0.001) during the time-out. CONCLUSIONS: Remote assessment using OR Black Box data provides useful insight into surgical safety checklist performance. Many items included in the time-out and debrief were not routinely discussed. Completion of a team introduction was associated with improved time-out performance. There is potential to use OR Black Box metrics to improve intraoperative process measures.

Cost Analysis and Financial Implications of a Peritoneal Surface Malignancy Program in the USA.

BACKGROUND: We aimed to describe the financial implications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in the USA. MATERIALS AND METHODS: We conducted a retrospective cost analysis of 100 CRS/HIPEC procedures to examine the impact of patient and procedural factors on hospital costs and reimbursement. A comparison of surgeons' work relative value units (wRVUs) between CRS/HIPEC and a representative sample of complex surgical oncology procedures was made to assess the physicians' compensation rate. Univariable and multivariable backward logistic regression was used to analyze the association between perioperative variables and high direct cost (HDCs). RESULTS: The median direct cost per CRS/HIPEC procedure was US $44,770. The median hospital reimbursement was US $43,066, while professional reimbursement was US $8608, resulting in a positive contribution margin of US $7493/procedure. However, the contribution margin significantly varied with the payer mix. Privately insured patients had a positive median contribution margin of US $23,033, whereas Medicare-insured patients had a negative contribution margin of US $13,034. Length of stay (LOS) had the most significant association with HDC, and major complications had the most significant association with LOS. Finally, CRS/HIPEC procedures generated a median of 13 wRVU/h, which is significantly lower than the wRVU/h generated by open pancreatoduodenectomies, open gastrectomies, and hepatectomies. However, higher operation complexity and multiple visceral resections help compensate for the relatively low wRVU/h. CONCLUSIONS: CRS/HIPEC is an expensive operation, and prolonged LOS has the most significant impact on the total cost of the procedure. High-quality care is essential to improve patient outcomes and maintain the economic sustainability of the procedure.

Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). PATIENTS AND METHODS: The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. RESULTS: Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. CONCLUSIONS: A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.

Racial and Ethnic Disparities in Access to Local Anesthesia for Inguinal Hernia Repair.

BACKGROUND: Many studies have identified racial disparities in healthcare, but few have described disparities in the use of anesthesia modalities. We examined racial disparities in the use of local versus general anesthesia for inguinal hernia repair. We hypothesized that African American and Hispanic patients would be less likely than Caucasians to receive local anesthesia for inguinal hernia repair. MATERIALS AND METHODS: We included 78,766 patients aged ≥ 18 years in the Veterans Affairs Surgical Quality Improvement Program database who underwent elective, unilateral, open inguinal hernia repair under general or local anesthesia from 1998-2018. We used multiple logistic regression to compare use of local versus general anesthesia and 30-day postoperative complications by race/ethnicity. RESULTS: In total, 17,892 (23%) patients received local anesthesia. Caucasian patients more frequently received local anesthesia (15,009; 24%), compared to African Americans (2353; 17%) and Hispanics (530; 19%), P < 0.05. After adjusting for covariates, we found that African Americans (OR 0.82, 95% CI 0.77-0.86) and Hispanics (OR 0.77, 95% CI 0.69-0.87) were significantly less likely to have hernia surgery under local anesthesia compared to Caucasians. Additionally, local anesthesia was associated with fewer postoperative complications for African American patients (OR 0.46, 95% CI 0.27-0.77). CONCLUSIONS: Although local anesthesia was associated with enhanced recovery for African American patients, they were less likely to have inguinal hernias repaired under local than Caucasians. Addressing this disparity requires a better understanding of how surgeons, anesthesiologists, and patient-related factors may affect the choice of anesthesia modality for hernia repair.

Local Anesthesia is Associated with Fewer Complications in Umbilical Hernia Repair in Frail Veterans.

BACKGROUND: The optimal anesthesia modality for umbilical hernia repair is unclear. We hypothesized that using local rather than general anesthesia would be associated with improved outcomes, especially for frail patients. METHODS: We utilized the 1998-2018 Veterans Affairs Surgical Quality Improvement Program to identify patients who underwent elective, open umbilical hernia repair under general or local anesthesia. We used the Risk Analysis Index to measure frailty. Outcomes included complications and operative time. RESULTS: There were 4958 Veterans (13%) whose hernias were repaired under local anesthesia. Compared to general anesthesia, local was associated with a 12%-24% faster operative time for all patients, and an 86% lower (OR 0.14, 95%CI 0.03-0.72) complication rate for frail patients. CONCLUSIONS: Local anesthesia may reduce the operative time for all patients and complications for frail patients having umbilical hernia repair.

Using local rather than general anesthesia for inguinal hernia repair may significantly reduce complications for frail Veterans.

BACKGROUND: Frailty predisposes patients to poor postoperative outcomes. We evaluated whether using local rather than general anesthesia for hernia repair could mitigate effects of frailty. METHODS: We used the Risk Analysis Index (RAI) to identify 8,038 frail patients in the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database who underwent elective, open unilateral inguinal hernia repair under local or general anesthesia. Our outcome of interest was the incidence of postoperative complications. RESULTS: In total, 5,188 (65%) patients received general anesthesia and 2,850 (35%) received local. Local anesthesia was associated with a 48% reduction in complications (OR 0.52, 95%CI 0.38-0.72). Among the frailest patients (RAI≥70), predicted probability of a postoperative complication ranged from 22 to 33% with general anesthesia, compared to 13-21% with local. CONCLUSIONS: Local anesthesia was associated with a ∼50% reduction in postoperative complications in frail Veterans. Given the paucity of interventions for frail patients, there is an urgent need for a randomized trial comparing effects of anesthesia modality on postoperative complications in this vulnerable population.

Using local rather than general anesthesia for inguinal hernia repair is associated with shorter operative time and enhanced postoperative recovery.

BACKGROUND: Inguinal hernia repair is the most common general surgery procedure and can be performed under local or general anesthesia. We hypothesized that using local rather than general anesthesia would improve outcomes, especially for older adults. METHODS: This is a retrospective review of 97,437 patients in the Veterans Affairs Surgical Quality Improvement Program who had open inguinal hernia surgery under local or general anesthesia. Outcomes included 30-day postoperative complications, operative time, and recovery time. RESULTS: Our cohort included 22,333 (23%) Veterans who received local and 75,104 (77%) who received general anesthesia. Mean age was 62 years. Local anesthesia was associated with a 37% decrease in the odds of postoperative complications (95% CI 0.54-0.73), a 13% decrease in operative time (95% CI 17.5-7.5), and a 27% shorter recovery room stay (95% CI 27.5-25.5), regardless of age. CONCLUSIONS: Using local rather than general anesthesia is associated with a profound decrease in complications (equivalent to "de-aging" patients by 30 years) and could significantly reduce costs for this common procedure.

Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update.

PURPOSE: The purpose of this guideline update is to incorporate recently reported practice-changing evidence into ASCO's recommendations on potentially curable pancreatic adenocarcinoma. METHODS: ASCO convened an Expert Panel to evaluate data from PRODIGE 24/CCTG PA.6, a phase III, multicenter, randomized clinical trial of postoperative leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) versus gemcitabine alone, presented at the 2018 ASCO Annual Meeting. In addition, PubMed was searched for additional papers that may influence the existing recommendations. RECOMMENDATIONS: The Expert Panel only updated Recommendation 4.1 as a result of the practice-changing data. Recommendation 4.1 states that all patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan (mFOLFIRINOX; oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 D1, and 5-fluorouracil 2.4 g/m2 over 46 hours every 14 days for 12 cycles) is now preferred in the absence of concerns for toxicity or tolerance; alternatively, doublet therapy with gemcitabine and capecitabine or monotherapy with gemcitabine alone or fluorouracil plus folinic acid alone can be offered.Additional information can be found at www.asco.org/gastrointestinal-cancer-guidelines.

Discrimination of low- and high-grade appendiceal mucinous neoplasms by targeted sequencing of cancer-related variants.

DNA was obtained from matching micro-dissected, primary tumor cells, paired metastases, and peripheral blood mononuclear cells (germline) from patients with appendiceal mucinous neoplasms. We compared specimens from patient cohorts comprising low-grade adenomucinous neoplasm versus high-grade mucinous adenocarcinoma using a targeted, amplicon sequencing panel of 409 cancer related genes (Ion Torrent Comprehensive Cancer Panel, Thermo-Fisher, Waltham, MA). Copy number variants, single nucleotide variants and small insertions/deletions were identified using a multiplex algorithm pipeline (GATK, VarScan2, MuTect2, SIFT, SIFT-INDEL, PolyPhen-2, Provean). There were significantly more damaging variants in high-grade versus low-grade tumor cohorts. Both cohorts contained damaging, heterozygous germline variants (catenin ß1; notch receptor 1 and 4) in pathways associated with cell-lineage specification (WNT, NOTCH). Damaging, somatic KRAS proto-oncogene, GTPase mutations were present in both cohorts, while somatic GNAS complex locus mutations were confined to low-grade neoplasms. Variants predominantly affected transcription factors, kinases, and stem cell signaling molecules in canonical pathways including epithelial to mesenchymal transition, stem cell pluripotency, p53, PTEN, and NF-қB signaling pathways. High-grade tumors demonstrated MYC proto-oncogene, bHLH transcription factor (MYC) and death domain associated protein (DAXX) amplification and damaging somatic variants in tumor protein p53 (TP53), likely to amplify an aggressive phenotype. Damaging APC, WNT signaling pathway regulator (APC) deletions were identified in metastatic tissue of both cohorts suggesting a role in invasive disease. Our data suggest that germline dysregulation of WNT and/or NOTCH pathways predisposes patients toward a secretory cell phenotype (i.e., goblet-like cells) upon acquisition of somatic KRAS mutations. Additional somatically acquired variants activating oncogenes MYC and DAXX and inhibiting the critical tumor suppressor, tumor protein TP53, were consistent with manifestation of a high-grade phenotype. These additional changes within the epithelial to mesenchymal transition signaling network (WNT, NOTCH, RAS/ERK/PI3K, PTEN, NF-қB), produce aggressive high-grade tumor characteristics by actively driving cells towards dedifferentiation, proliferation, and migration.

Repeat Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemoperfusion is Feasible and Offers Survival Benefit in Select Patients with Peritoneal Metastases.

INTRODUCTION: We hypothesized that repeat cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) for peritoneal metastases (PM) may be associated with suboptimal resection, more frequent postoperative complications, and worse oncologic outcomes. METHODS: Using a prospectively maintained database, we compared clinicopathologic, perioperative, and oncologic outcome data in patients undergoing single or repeat CRS-HIPEC procedures. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. RESULTS: Of the 1294 patients undergoing CRS-HIPEC procedures at our institution, only one CRS-HIPEC procedure (single HIPEC cohort) was performed in 1169 patients (90.3%), whereas 125 patients (9.7%) underwent repeat CRS-HIPEC procedures (repeat HIPEC cohort). Of the 1440 CRS-HIPEC procedures at our institution, a first CRS-HIPEC procedure was performed in 1294 patients (89.9%), whereas subsequent second, third, and fourth CRS-HIPEC procedures were performed in 125 patients (8.7%), 18 patients (1.3%), and 3 patients (0.2%), respectively. Progression-free survival (PFS) following the second CRS-HIPEC procedure was negatively impacted by shorter PFS following the first CRS-HIPEC procedure, independent of other significant variables related to the second procedure, including completeness of cytoreduction and postoperative complications. Patients undergoing multiple CRS-HIPEC procedures were not at higher risk for suboptimal resection or postoperative complications and demonstrated equivalent PFS following each successive procedure compared to the first procedure. CONCLUSIONS: Repeat CRS-HIPEC procedures for PM were not associated with suboptimal perioperative and oncologic outcomes. Our data confirmed our ability to select patients appropriately for repeat CRS-HIPEC procedures.

Pleuropulmonary Recurrence Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Appendiceal Pseudomyxoma Peritonei.

BACKGROUND: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. METHODS: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. RESULTS: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). CONCLUSION: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes.

Postoperative Complications Independently Predict Cancer-Related Survival in Peritoneal Malignancies.

BACKGROUND: The authors hypothesized that postoperative complications after cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) have a negative impact on perioperative and oncologic outcomes and that the novel Comprehensive Comorbidity Index (CCI) would be a better predictor of such outcomes than the traditional Clavien-Dindo classification (CDC). METHODS: The study used a prospective database of 1296 patients with peritoneal metastases (PM) undergoing CRS-HIPEC between 2001 and 2016. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. The Akaike information criterion and the Schwarz (Bayesian information) criterion were used to compare model fitting for CCI versus CDC. RESULTS: In this study, CRS-HIPEC was performed for malignant mesothelioma (12%) and PM from appendix (50%), colorectal (30%), and ovarian (8%) cancers. Major postoperative in-hospital complications (CDC grades 3-4) occurred for 24% of the patients. However, a range of CCI scores was calculated for each CDC grade because 36% of the patients experienced multiple complications. After a median follow-up period of 55 months, the median progression-free survival was 15 months, and the median overall survival was 39 months. In the multivariate Cox proportional hazards models, postoperative in-hospital complications (measured by CDC or CCI) were independent prognostic factors for 30-day post-discharge morbidity and readmission, as well as for survival. The CCI scores demonstrated higher prognostic sensitivity for these outcomes than CDC grades. CONCLUSIONS: Reduction of postoperative complications after CRS-HIPEC is essential for optimal short- and long-term outcomes. For assessing total burden of postoperative complications per patient, CCI is superior to CDC and more sensitive for assessing surgery- and cancer-related outcomes after CRS-HIPEC.

Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer. How I do It.

Approximately 30% of all pancreatic cancer patients have locally advanced (AJCC stage 3) disease. A sub-group of these patients-where the cancer only involves the celiac axis-may benefit from distal pancreatectomy with celiac axis resection (DP-CAR). Previous studies have shown that DP-CAR offers a survival benefit to a selected group of patients with otherwise unresectable pancreatic cancer, when performed by experienced pancreatic cancer treatment teams at high-volume centers. This article proposes a standardized approach to DP-CAR, including routine neoadjuvant (FOLFIRINOX) chemotherapy. This approach to selecting patients and performing DP-CAR has the potential to improve short-term outcomes and overall survival in selected patients, but it should be reserved for high-volume centers.

FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma.

BACKGROUND: Both FOLFIRINOX and gemcitabine/nab-paclitaxel (G-nP) are used increasingly in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA). This study aimed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable (R) and borderline resectable (BR) head PDA. METHODS: A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed. Comparative analysis was performed using inverse-probability-weighted (IPW) estimators. The end points of the study were overall survival (OS) and an 80% reduction in CA19-9 with NAT. RESULTS: In this study, 193 patients were analyzed, with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP (p = 0.214). The patients who received FOLFIRINOX were younger and had fewer comorbidities, more BR disease, and larger tumors than those treated with G-nP (all p < 0.05). The two regimens were equally effective in achieving an 80% decline in CA19-9 (p = 0.8). The R0 resection rates were similar (80%), but FOLFIRINOX was associated with a reduction in pN1 disease (56% vs. 72%; p = 0.028). The receipt of adjuvant therapy was similar (74 vs. 75%; p = 0.79). In the Cox regression analysis with adjustment for baseline and treatment-related variables (FOLFIRINOX vs. G-nP, age, gender, computed tomography (CT) tumor size, BR vs. R, pre-NAT CA19-9), regimen type was not associated with a survival benefit. In the IPW analysis of 166 patients, however, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP (p = 0.012). CONCLUSIONS: Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA. In this study, neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates.

Impact of Cellularity on Oncologic Outcomes Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Pseudomyxoma Peritonei.

BACKGROUND: The Peritoneal Surface Oncology Group International (PSOGI) recommends pathologic reporting of tumor cellularity in patients with pseudomyxoma peritonei (PMP) undergoing cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC). We investigated the prognostic significance of PMP cellularity, or lack thereof (acellular mucin), following CRS-HIPEC. METHODS: We reviewed clinical data for 310 CRS-HIPEC procedures in low-grade (American Joint Committee on Cancer grade G1) PMP with acellular mucin (n = 19), scant cellularity (n = 30), or moderate cellularity (n = 242). Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS: Compared with patients with acellular mucin, those with scant and moderate cellularity had higher PCI and less-frequent complete macroscopic resection. After an estimated median follow-up of 49 months, 4 patients (14%) with scant cellularity and 127 patients (56%) with moderate cellularity progressed, while none of the patients with acellular mucin progressed. While the median progression-free survival (PFS) was not reached for patients with acellular mucin or scant cellularity (estimated 5-year PFS probability of 100 and 83%, respectively), patients with moderate cellularity demonstrated a median PFS of 32 months (estimated 5-year PFS probability of 27%). In a multivariate model, degree of disease cellularity, or lack thereof (acellular mucin), was an independent predictor of PFS but not overall survival. CONCLUSIONS: Early disease progression is unlikely in patients with acellular mucin undergoing CRS-HIPEC, as opposed to a 14% recurrence rate with scant cellularity. Thorough pathologic assessment for cellularity, or lack thereof (acellular mucin), is vital for accurate prognostication of disease progression for patients with low-grade PMP undergoing CRS-HIPEC.

Institutional Experience with Ostomies Created During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) is a complex procedure that often requires ostomy creation to protect high-risk anastomoses. This study aimed to evaluate the authors' institutional experience with CRS-HIPEC-associated ostomies, determine predictors of ostomy creation and reversal, and assess their impact on survival. METHODS: The study analyzed clinicopathologic, perioperative, and oncologic data from a prospective database of 1435 CRS-HIPEC procedures for peritoneal metastases. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with ostomy creation/reversal and survival. RESULTS: Ostomies were created in 34% of the patients, most commonly loop ileostomies (82%). Loop ileostomies were reversed in the majority of patients (83%), whereas non-loop ileostomies were infrequently reversed (< 10% reversal rate). In a multivariate logistic regression model, intermediate or high tumor grade, colectomy/proctectomy, longer operative time, and lower Charlson comorbidity index were associated with loop ileostomy creation, whereas incomplete macroscopic resection, colorectal histology, and major postoperative complications were associated with non-reversal of loop ileostomy. In a multivariate Cox proportional hazards model, intermediate or high tumor grade and non-reversal of loop ileostomy were associated with worse overall survival. CONCLUSIONS: Loop ileostomies were almost always reversed, whereas non-loop ileostomies were almost always permanent. Hospital readmissions for loop ileostomy-related complications were common. Therefore, formal outpatient protocols for prevention and management should be implemented. Non-reversal of loop ileostomy was associated with very poor survival.

Safety and efficacy of combined resection of colorectal peritoneal and liver metastases.

BACKGROUND: To determine if a select subgroup of patients with combined liver and peritoneal colorectal metastases would derive oncologic benefit from surgical resection as a component of multimodality treatment. MATERIALS AND METHODS: We retrospectively compared 32 patients with combined colorectal peritoneal and liver metastases (CRLM) and 173 patients with peritoneal metastases only (CRPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC). Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting survival. RESULTS: Major postoperative complications (Clavien-Dindo grades 3-5) occurred in 32% (CRLM) and 17% (CRPM) of patients (P = 0.08). After an estimated median follow-up from surgery of 57 mo, propensity score-adjusted median progression-free survival was 5.1 mo (CRLM) and 7.6 mo (CRPM), whereas median overall survival was 13 mo (CRLM) and 21 mo (CRPM). Multivariate Cox-regression analysis of the CRLM group identified number of liver metastases to be the only independent predictor of poor survival (hazard ratio: 2.3, P = 0.03), with a dramatic decrease in survival in patients with more than three liver metastases. CONCLUSIONS: Simultaneous resection of colorectal liver metastases at the time of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion for peritoneal metastases may be associated with worse survival, especially in patients with more than three liver metastases.

Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival.

PURPOSE: Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC. METHODS: Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1-5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference. RESULTS: A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1-5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P < 0.0001), tumor stage [hazard ratio (HR) 1.35], LNR (HR 4.3), and R1 margins (HR 1.77) were associated with increased hazard of death. Compared with 6 cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47-5.18] or 1-5 cycles in any combination (HR 2.37, CI 1.73-3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78-1.47). CONCLUSIONS: Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

Hyperthermic intraperitoneal chemoperfusion as a component of multimodality therapy for ovarian and primary peritoneal cancer.

BACKGROUND AND OBJECTIVES: The role of hyperthermic intraperitoneal chemoperfusion (HIPEC) in the multimodality treatment of ovarian peritoneal metastases (OPM) and primary peritoneal cancer (PPC) remains controversial. We hypothesized that cytoreductive surgery (CRS) and HIPEC would provide meaningful survival benefit without excessive morbidity. METHODS: We reviewed clinicopathologic and perioperative data following 96 CRS-HIPEC procedures for primary or recurrent OPM and PPC. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: CRS-HIPEC was mostly performed for recurrent disease (56.3%) and high-grade serous carcinoma (72.9%). Platinum-based systemic chemotherapy was administered to 89.5% of patients, with 75.5% having platinum-sensitive disease at CRS-HIPEC. Complete macroscopic resection was achieved in 70.8% of patients. Clavien-Dindo grade 3/4 morbidity occurred in 23.4% of patients; three patients died within 60-days postoperatively. Median overall survival from diagnosis of peritoneal metastases and CRS-HIPEC was 78 and 38 months, respectively. Completeness of cytoreduction, pathologic subtype, and 30-day morbidity were independent predictors of survival in multiple regression analysis. CONCLUSIONS: Our study demonstrates promising survival data and supports the role of HIPEC in the multimodality treatment algorithm for primary or recurrent OPM and PPC. However definite indications and timing of HIPEC need to be clarified by prospective studies.

Failure to Treat: Audit of an Institutional Cancer Registry Database at a Large Comprehensive Cancer Center Reveals Factors Affecting the Treatment of Pancreatic Cancer.

BACKGROUND: National Cancer Database analysis showed 70% of patients with stage I pancreatic adenocarcinoma (PDA) did not have surgery. We sought to analyze adherence to expected treatment (ET) by stage for PDA and identify factors that led to no treatment (NT) or unexpected treatment (UT) in a recent cohort. METHODS: Using our Institutional Cancer Registry (ICR), we identified patients with PDA from 2004 to 2013. ET was defined as surgery ± chemotherapy ± radiation for stages I and II, chemotherapy ± radiation for stage III, and chemotherapy for stage IV, while UT was defined as no surgery for stages I and II, surgery for stage III, or ± surgery ± XRT for stage IV. RESULTS: Overall, 2340 patients were identified (stages I and II = 51%, stage III = 11%, stage IV = 38%; ET = 58%, UT = 18%, NT = 24%). A total of 1183 patients had resectable PDA (stages I and II; ET = 57%, UT = 27%, NT = 16%), with ET demonstrating the best overall survival, but UT showing better survival than NT (p < 0.0001). In addition, 261 patients had unresectable PDA (stage III; ET = 69%, UT = 12%, NT = 18%), and survival was best in UT, but ET had a survival advantage over NT (p < 0.0001). Finally, 896 patients had metastatic PDA (stage IV; ET = 55%; UT = 9%; NT = 36%), with the NT group showing worse survival than the ET and UT groups (p < 0.0001). CONCLUSIONS: Unlike previous reports, most patients with early-stage disease had ET. ET and UT were associated with better survival than NT in all stages, and surgical cohorts have improved survival regardless of stage. Younger age, male sex, white race, and less comorbidity were predictors of receiving treatment.