Acute cholecystitis, obesity, and steatohepatitis constitute the lethal triad for bile duct injury (BDI) during laparoscopic cholecystectomy.

OBJECTIVE: The most feared complication during laparoscopic cholecystectomy remains a bile duct injury (BDI). Accurately risk-stratifying patients for a BDI remains difficult and imprecise. This study evaluated if the lethal triad of acute cholecystitis, obesity, and steatohepatitis is a prognostic measure for BDI. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry was performed. All laparoscopic cholecystectomy cases within the main NSQIP database for 2012-2019 were queried. Two study cohorts were constructed. One with the lethal triad of acute cholecystitis, BMI ≥ 30, and steatohepatitis. The other cohort did not have the full triad present. Multivariate analysis was performed via logistic regression modeling with calculation of odds ratios (OR) to identify independent factors for BDI. An uncontrolled and controlled propensity score match analysis was performed. RESULTS: A total of 387,501 cases were analyzed. 36,887 cases contained the lethal triad, the remaining 350,614 cases did not have the full triad. 860 BDIs were identified resulting in an overall incidence rate 0.22%. There were 541 BDIs within the lethal triad group with 319 BDIs in the other cohort and an incidence rate of 1.49% vs 0.09% (P < 0.001). Multivariate analysis identified the lethal triad as an independent risk factor for a BDI by over 15-fold (OR 16.35, 95%CI 14.28-18.78, P < 0.0001) on the uncontrolled analysis. For the controlled propensity score match there were 29,803 equivalent pairs identified between the cohorts. The BDI incidence rate remained significantly higher with lethal triad cases at 1.65% vs 0.04% (P < 0.001). The lethal triad was an even more significant independent risk factor for BDI on the controlled analysis (OR 40.13, 95%CI 7.05-356.59, P < 0.0001). CONCLUSIONS: The lethal triad of acute cholecystitis, obesity, and steatohepatitis significantly increases the risk of a BDI. This prognostic measure can help better counsel patients and potentially alter management.

Exposure to Neoadjuvant Oxaliplatin-Containing Chemotherapy, Does it Effect Intraperitoneal Hyperthermic Chemotherapy Perfusion?

INTRODUCTION: Patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are commonly exposed to oxaliplatin neoadjuvant chemotherapy (NAT) regimens. The impact of systemic exposure to oxaliplatin prior to HIPEC with oxaliplatin is unknown. METHODS: We conducted a retrospective review of our institutional registry of CRS/HIPEC cases who received oxaliplatin-containing NAT, and compared patients who underwent HIPEC with oxaliplatin versus cases perfused with mitomycin C. The primary outcome was survival, defined by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was performed based on primary tumor etiology and completeness of cytoreduction. RESULTS: A total of 333 cases satisfied the selection criteria-159 appendiceal primaries (all high-grade disease) and 174 colorectal cases. Thirty-one cases (9.3%) underwent HIPEC with oxaliplatin, with the remaining 302 cases (90.7%) receiving mitomycin C. Both cohorts were identical in regard to baseline characteristics, and both groups were alike in regard to NAT regimens and oxaliplatin exposure. There was no difference in survival outcomes. OS times were 2.9 (± 2.8) and 2.8 ( ± 3.6) years for oxaliplatin and mitomycin C perfusions, respectively (p = 0.94), and the 5-year OS rates were also similar at 9.7 and 18.5% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.14-1.67, p = 0.24) for oxaliplatin and mitomycin cases, respectively. Likewise, DFS findings were similar, with survival of 2.5 (± 4.5) and 1.8 (± 2.4) years for oxaliplatin and mitomycin perfusions, respectively (p = 0.21). There was no difference in 5-year DFS rates, at 10.5 and 7.8% (OR 1.39, 95% CI 0.30-6.56, p = 0.68) for oxaliplatin and mitomycin C, respectively. Subgroup analysis found minimal discordant findings from the main results. CONCLUSION: This analysis found no discernable association with NAT oxaliplatin exposure in regard to survival outcomes following CRS/HIPEC stratified out by perfusion agent.

Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Surgical Dogma or Evidence-Based Practice?

BACKGROUND: A common practice is to switch chemotherapy perfusion agents for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, there is a paucity of objective benefit with this practice. METHODS: A retrospective review of our institutional registry involving repeat CRS-HIPEC cases was conducted, comparing cases that underwent a perfusion agent switch versus those cases with no switch. The primary outcome of this study was survival, measured by overall survival (OS) and disease-free survival (DFS). A subgroup analysis was performed on the basis of primary etiology. RESULTS: A total of 101 cases met selection criteria. Mitomycin C was used as the index perfusion agent in 84% of cases, while oxaliplatin was utilized in the remaining 16% of cases. In total, 66 cases underwent a perfusion switch, with 35 cases using the same agent. Analysis revealed no survival benefit with HIPEC perfusion switch. For OS, there were similar mean survival times of 5.2 (± 4.1) years and 5.1 (± 3.6) years for cases with perfusion switch and no perfusion switch, respectively (P = 0.985). The 5-year OS rates were also similar at 61.4% and 53.3% for switch and non-switch cases, respectively [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.54-3.56, P = 0.49]. Mean DFS was 4.0 (± 4.2) years and 3.6 (± 3.8) years for switch and non-switch cases, respectively (P = 0.74). The 5-year DFS rates had a greater difference with statistical trend, with rates of 53% versus 28% for switch and non-switch cases, respectively (OR 2.91, 95% CI 0.86-9.86, P = 0.081). Subgroup analysis had a similar trend to the main results. CONCLUSIONS: The study findings revealed no survival benefit with switching perfusion agents. Analysis suggests that the practice of perfusion switch is ineffective.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Impact of myometrium invasion on survival outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective surgical intervention for peritoneal surface malignancy. The effect of myometrium invasion on outcomes is unknown. METHODS: Retrospective review of our institutional registry with analysis of CRS-HIPEC cases involving a hysterectomy. Compared cases with myometrium invasion versus those without invasion. Primary outcome was survival as measured by overall survival (OS) and disease-free survival (DFS). Secondary outcome was the evaluation of risk factors for myometrium invasion based on multivariate analysis. RESULTS: A total of 126 cases of CRS-HIPEC involving a hysterectomy were identified. Ninety-seven cases (76.9%) had no myometrium invasion and the remaining 29 cases (23.1%) had malignant invasion. The presence of myometrial invasion was a significant negative survival prognostic factor. The OS was halved with mean survival times of 2.8 (±2.3) versus 5.8 (±4.7) years for cases with and without invasion, respectively (p = 0.002). Five-year OS rates were also inferior with myometrium invasion at 17.4% versus 53.8% (odds ratio [OR] = 0.181, 95% confidence interval [CI]: 0.057-0.580, p = 0.002). A similar trend was present with DFS with mean survival times of 1.4 (±0.9) versus 3.7 (±3.9) years for noninvasion and invasion cases (p = 0.009). The 5-year DFS rates were 0% versus 34.8% (OR = 0.652, 95% CI: 0.549-0.775, p = 0.004). Secondary analysis significantly associated several risk factors with myometrium invasion to include lymph node positivity (OR = 2.539, 95% CI: 1.074-6.003, p = 0.012), colorectal primary tumors (OR = 2.248, 95% CI: 1.094-5.161, p = 0.035), and high-grade tumors (OR = 2.160, 95% CI: 1.080-4.820, p = 0.038). CONCLUSION: Myometrium invasion is a significant negative prognostic factor for survival following CRS-HIPEC. Several risk factors are potentially predictive of identifying those at high-risk for myometrium invasion.

Comparison of survival for metastatic pancreatic cancer patients treated with CPI-613 versus resected borderline-resectable pancreatic cancer patients.

INTRODUCTION: Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS: A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS: There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION: The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

Risk factors and outcomes for cholangitis after hepatic resection.

INTRODUCTION: There is a paucity in the literature in regard to the incidence, risk factors, and outcomes for post-operative cholangitis following hepatic resection. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2012-2016. RESULTS: A total of 11,243 cases met the selection criteria. The incidence of post-operative cholangitis was 0.64% (151 cases). Multivariate analysis identified several risk factors associated with the development of post-operative cholangitis, stratified out by pre-operative and operative factors. The most significant risk factors were biliary anastomosis and pre-operative biliary stenting with odds ratios (OR) of 32.39 (95% CI 22.91-45.79, P value < 0.0001) and 18.32 (95% CI 10.51-31.94, P value < 0.0001) respectively. Cholangitis was significantly associated with post-operative bile leaks, liver failure, renal failure, organ space infections, sepsis/septic shock, need for reoperation, longer length of stay, increased readmission rates, and death. CONCLUSION: Largest analysis of post-operative cholangitis following hepatic resection. While a rare occurrence, it is associated with significantly increased risk for severe morbidity and mortality. The most significant risk factors were biliary anastomosis and stenting.

Prognostic Effect of Aberrant Right Hepatic Artery with Pancreaticoduodenectomy: Focus on Hepatic Recurrence.

INTRODUCTION: Metastatic progression occurs along the locoregional vasculature, and a common anatomic variant is an aberrant right hepatic artery (aRHA). This study evaluated the effect of an aRHA following pancreaticoduodenectomy, with a focus on hepatic metastases. METHODS: This was a single-institution retrospective review of non-metastatic pancreatic cancer cases between 2012 and 2020. aRHA cases were compared with patients with conventional anatomy. The primary outcome was hepatic recurrence rates, while secondary analysis survival outcomes were measured by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was stratified by tumor resectability and utilization of systemic therapy. RESULTS: Overall, 207 cases were reviewed, with 17.4% having aRHA anatomy. On multivariate analysis, aRHA increased hepatic recurrence for all-comers (odds ratio [OR] 4.76, 95% confidence interval [CI] 2.18-10.38; p < 0.001). aRHA was significant for resectable tumors (OR 2.58, 95% CI 1.89-6.66; p = 0.045) and borderline resectable tumors (OR 28.88, 95% CI 5.52-151.18; p < 0.0001) in regard to hepatic recurrence on univariate analysis. Increased hepatic recurrence correlated with decreased 3-year OS and DFS rates of 30.6% versus 50.3% (OR 0.44, 95% CI 0.20-0.94; p = 0.032) and 13.6% versus 36.9% (OR 0.27, 95% CI 0.08-0.97; p = 0.035). Systemic therapy limited the effects of aRHA. CONCLUSION: aRHA was associated with inferior survival outcomes due to the significantly increased risk of hepatic metastatic disease with aberrant anatomy. This study provides important prognostic information for a commonly encountered anatomic variant.

Incidence, Risk Factors, and Outcomes from Conversion of Low-Grade to High-Grade Appendiceal Neoplasms for Patients Undergoing Multiple Cytoreductive Surgeries with Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Conversion from low-grade to high-grade disease is known to occur following repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC); however, the incidence rate, risk factors, and outcomes have not been studied. METHODS: We conducted a retrospective review of multiple CRS/HIPEC cases for patients originally diagnosed with low-grade appendiceal neoplasms, and compared converted cases with non-converters. Primary outcomes were the incidence rate and risk factors for conversion, while secondary outcomes were effect on cytoreduction, overall survival (OS), and disease-free survival (DFS). RESULTS: Overall, 65 patients undergoing 134 cases of repeat CRS/HIPEC were identified; 11 patients converted to high-grade disease, an incidence rate of 16.92%. Converted cases averaged 4.4 years between CRS/HIPEC, versus 3.7 years for non-converters. Elevated baseline carcinoembryonic antigen (CEA) level, splenectomy at index CRS/HIPEC, and adjuvant chemotherapy utilization were statistically significant with conversion. Conversion had no impact on specific cytoreductive scores at repeat CRS/HIPEC (p = 0.435). Evaluating the effect on OS from the index CRS/HIPEC conversion had no impact. Mean OS was 9.5 and 8.8 years for cases that remained low-grade compared with those that converted, respectively (p = 0.668); however, when comparing OS from the time of conversion at repeat CRS/HIPEC, patients who progressed to high-grade disease had decreased survival at 4.4 versus 5.8 years (p = 0.0317). There was no difference in DFS between non-converters and converters at 4.1 and 3.6 years, respectively (p = 0.671). CONCLUSION: Conversion had no impact on OS from the index CRS/HIPEC but resulted in inferior survival from repeat surgery. Conversion was insignificant in regard to DFS, and should not be considered a contraindication to repeat CRS/HIPEC. Adjuvant chemotherapy should be avoided.

Utility of Neoadjuvant Chemotherapy for Peritoneal Carcinomatosis Secondary to High-Grade Appendiceal Neoplasms for Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Neoadjuvant chemotherapy (NAT) is frequently utilized before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for high-grade appendiceal neoplasms. The proposed benefits of NAT do not correlate with the limited literature. METHODS: Retrospective review of our CRS-HIPEC registry. Primary outcomes were the effect of NAT on disease burden, cytoreduction scores, overall survival (OS), disease-free survival (DFS), and recurrence patterns. RESULTS: A total of 126 cases of high-grade disease met selection criteria; 73 cases received NAT before referral, and 53 cases received no therapy before referral and went directly to CRS-HIPEC. For those cases who received NAT 89% received a FOLFOX-based regimen. Mean PCI scores were 16.47 and 16.07 (P = 0.843) with complete cytoreductions rates of 79.5% and 75% (P = 0.556) for NAT and non-NAT cases, respectively. NAT cases were associated with significantly decreased OS and DFS rates. Mean OS was 3.6 and 2.5 years (P = 0.005) with actual 5-year OS rates of 24.2% versus 5% (P = 0.017) for non-NAT and NAT cases respectively. Mean DFS was 2.8 and 1.7 years (P = 0.015) with actual 5-year DFS rates of 18.6% versus 5.7% (P = 0.048) for non-NAT and NAT cases respectively. Lastly, the use of NAT had no impact on recurrence patterns (P = 0.221). CONCLUSIONS: This is the largest study to evaluate high-grade appendiceal neoplasms in regard to CRS-HIPEC and NAT. NAT had no impact in regard to disease burden, cytoreduction, or recurrence patterns. Utilization of NAT was associated with decreased OS and DFS.

Timing of Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Recurrent Low-Grade Appendiceal Mucinous Neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) with peritoneal involvement is a common indication for cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC). With peritoneal recurrence, patients are increasingly being offered repeat CRS/HIPECs, however optimal timing for a second CRS/HIPEC remains unknown. METHODS: A prospectively maintained 30-year database at our high-volume HIPEC center was analyzed retrospectively for patients with LAMNs and peritoneal recurrence receiving one or two CRS/HIPECs. Kaplan-Meier survival analysis, linear regression modeling, and Cox proportional hazards regression analyses were performed. RESULTS: Overall, 143 patients with LAMNs who underwent CRS/HIPECs had confirmed postoperative peritoneal recurrence. Of these patients, 85 underwent one CRS/HIPEC and 58 underwent two CRS/HIPECs. The groups had significant differences in age, with younger patients more likely to undergo a second CRS/HIPEC (48.5 vs. 58.0 years; p < 0.001). The median overall survival (OS) for the group undergoing two CRS/HIPECs was approximately four times longer compared with the group undergoing one CRS/HIPEC (227.1 vs. 54.5 months; p < 0.0001). The time from recurrence to the second CRS/HIPEC was not significantly associated with OS from the time of the first operation. Instead, a shorter time between the first CRS/HIPEC and recurrence was significantly associated with shorter OS from the time of the first operation (p = 0.037). CONCLUSION: In peritoneal LAMNs with recurrence, receiving two CRS/HIPECs was associated with better OS compared with receiving one CRS/HIPEC. Longer time to recurrence was a good prognostic factor. Delay between recurrence and second CRS/HIPEC had no apparent impact on OS from the first CRS/HIPEC; thus, immediate or delayed reoperative intervention are both reasonable approaches.

Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Cancers with Peritoneal Metastasis: A 30-year Institutional Experience.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival in abdominal cancer patients with metastatic disease limited to the peritoneal cavity. Patients are increasingly being offered repeat CRS-HIPECs for peritoneal recurrence. However, in this rare clinical scenario, the survival benefit of performing repeat CRS-HIPEC operations remains unclear. METHODS: A retrospective review of the CRS-HIPEC database at Wake Forest Baptist Medical Center was performed over a 30-year timespan. From 1547 patients with appendix cancers, colorectal cancers, mesotheliomas, and other miscellaneous cancers, 156 received more than one CRS-HIPEC. Kaplan-Meier survival analysis was performed using overall survival (OS) from the time of surgery as the primary endpoint. Multi-variable Cox proportional hazards regression modelling was performed on pertinent clinical variables. RESULTS: Patients who received multiple CRS-HIPECs had significantly better median OS (10.7 years) versus those who received one CRS-HIPEC (2.5 years), with appendix cancers faring best (12.9 years). Resection status R2a or better was achieved in 76.4% of repeat CRS-HIPECs. There were no significant changes in complication rates after repeat CRS-HIPEC. On multivariate analysis of repeat CRS-HIPEC, patients with appendix and colorectal cancers, heart disease, and poor functional status were independently associated with poor OS. Factors not independently associated with OS were age, sex, body mass index, race, diabetes, lung disease, smoking history, and systemic chemotherapy between CRS-HIPECs. CONCLUSIONS: Performing multiple CRS-HIPEC operations on appropriate surgical candidates may significantly prolong survival. Appendix cancers derived the greatest benefit. Satisfactory resection margins and complication rates are comparable to first cases and achievable in repeat CRS-HIPEC procedures.

Utility of hyperthermic intraperitoneal chemotherapy in cases of incomplete cytoreductive surgery.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions. METHODS: Retrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score. RESULTS: A total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS-HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS-HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low-grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS-HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC. CONCLUSION: HIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low-grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

BACKGROUND: Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS: Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION: Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.

Utilization of combination bowel preparation (CBP) is protective against the development of post-operative Clostridium difficile infection (CDI), decreases septic complications, and provides a survival benefit.

BACKGROUND: The current standard recommended by the American Society of Colon and Rectal Surgeons (ASCRS) is to utilize a combined bowel preparation (CBP) that involves both mechanical (MBP) and oral antibiotic (ABP) components. The current literature is equivocal on whether ABP predisposes to post-operative Clostridium difficile infection (CDI). CDI following colorectal surgery is a significant complication leading to increase in significant morbidity and mortality. Objective was to further delineate the association between CBP and CDI. METHODS: Retrospective review of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) registry was performed. Specifically the main and targeted colectomy/proctectomy databases for 2015 and 2016 were analyzed. 64,449 colorectal surgeries were contained. Exclusion of non-elective cases and cases that did not utilize a bowel preparation or used ABP alone resulted in 24,000 cases for final analysis. Primary endpoint was post-operative CDI development. Secondary analysis involved surgical site infections (SSIs), anastomotic leaks, and sepsis development. 30-day mortality rates, rapidity of return of bowel function, and length of stay were also evaluated. RESULTS: Approximately two-thirds of the cases analyzed involved CBP and the remaining third used MBP alone. Cases that utilized CBP had statistically significant lower rates of all infectious complications evaluated. CBP was found to be protective in regard to the development of CDI with an odds ratio (OR) of 0.58. Our results collaborate the current literature that CBP decreases SSIs and anastomotic leaks with ORs of 0.58 and 0.79, respectively. CBP had its most profound effect on lowering septic shock and mortality rates halving the incidence of both. CONCLUSION: Our findings support the ASCRS guidelines for routine utilization of CBP to optimize post-operative outcomes. CBP does not increase the risk of CDI and in fact is significantly protective. CBP potentially also provides decreased risk of sepsis and mortality.

Utilization of chemoradiation therapy provides strongest protective effect for avoidance of postoperative pancreatic fistula following pancreaticoduodenectomy: A NSQIP analysis.

BACKGROUND: The utilization of neoadjuvant therapy (NAT) before performing pancreaticoduodenectomy for malignancy has been well established as a protective factor for the prevention of postoperative pancreatic fistula (POPF). However, there is a paucity of published data evaluating the specific NAT regimen that is the most protective against POPF development. We evaluated the differences between neoadjuvant chemotherapy (CT) and chemoradiation therapy (CRT) with regard to the effect on POPF rates. METHODS: The main and targeted pancreatectomy American College of Surgeons National Surgical Quality Improvement Program registries for 2014-2016 were retrospectively reviewed. A total of 10,665 pancreaticoduodenectomy cases were present. The primary outcome was POPF development. The factors that have previously been shown to be associated with or suspected to be associated with POPF were evaluated. The factors included NAT, sex, age, body mass index (BMI), diabetes, smoking, steroid therapy, preoperative weight loss, preoperative albumin level, perioperative blood transfusions, wound classification, American Society of Anesthesiologists classification, duct size (<3 mm, 3-6 mm, and >6 mm), gland texture (soft, intermediate, and hard), and anastomotic technique. The factors identified to be statistically significant were then used for propensity score matching to compare POPF development between the cases utilizing CT versus CRT. RESULTS: A total of 10,117 cases met the inclusion criteria. The development of POPF was significantly associated, on multivariate analysis, with a lack of NAT, male sex, higher BMI, nondiabetic status, nonsmoker status, decreased weight loss, preoperative albumin level, decreased duct size, and soft gland texture. NAT, duct size, and gland texture had the strongest associations with the development of POPF (p < .0001). The overall 1765 cases (17.45%) received NAT and the POPF rate for cases with NAT was 10.20% versus 20.10% for cases without NAT (p < .0001). A total of 1031 cases underwent CT and 734 cases underwent CRT, respectively. A total of 708 paired cases were selected for analysis based on propensity score matching. The POPF rates were 11.20% versus 3.50% for CT and CRT, respectively (p < .0001). There was no difference in the frequencies of specific POPF grades. The decreased POPF rate with CRT correlated with firmer gland texture rates. CONCLUSIONS: To our knowledge, this is the largest analysis of specific NAT regimens with regard to the development of POPF following pancreaticoduodenectomy. CRT provided the strongest protective effect. That protective effect is most likely due to increased fibrosis in the pancreatic parenchyma from radiation therapy. These findings provide additional support to consider CRT over CT alone in the treatment of pancreatic cancer when NAT will be utilized.

Surgical drain placement in distal pancreatectomy is associated with an increased incidence of postoperative pancreatic fistula and higher readmission rates.

BACKGROUND: Postoperative pancreatic fistula (POPF) can result in significant morbidity after distal pancreatectomy (DP). It is common practice to place prophylactic surgical drains during DP to monitor and minimize POPF complications; however, their use is controversial. OBJECTIVE: The aim of this study is to determine if drainage helps to prevent adverse outcomes and decrease the need for additional interventions after DP. METHODS: All patients who underwent DP without vascular resection were identified in the 2014 Targeted Pancreatectomy American College of Surgeons National Surgery Quality Improvement Program Participant Use File. Patients undergoing emergency procedures, American Society of Anesthesiology (ASA) 5, or diagnosed with preoperative sepsis were excluded. Univariate and multiple variable analyses were performed to evaluate postoperative outcomes based on use of surgical drain. RESULTS: A total of 1158 patients (age median: 62; interquartile range: 16; female 58.6%) underwent elective DP with 85.1% (n = 985) having drain placed at time of operation. Laparoscopic technique was used in the majority of patients (54.1%, n = 619). POPF occurred in 201 patients (17.5%). Additional percutaneous drain was required in 106 patients (9.2%). POPF was higher in surgical drain group, 19.4% vs 6.9% (P < .001). Need for percutaneous drain was similar between drain and no drain groups, 9.3% vs 8.1% (P = .600). Postoperative sepsis, shock, major complication, reoperation, and 30-day mortality was similar between drain and no drain groups (all P > .05). However, readmission was higher in the surgical drain group, 17.8% vs 10.4% (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.1; P = .018). After adjusting for age, ASA, and operative time, readmission remained higher in the surgical drain group (OR: 1.9; 95% CI: 1.1-3.2; P = .016). CONCLUSION: The use of surgical drainage during DP was associated with increased incidence of readmission and POPF. Drainage showed no effect on outcomes of postoperative sepsis, shock, major complications, reoperation, and 30-day mortality. Based on these results, routine prophylactic drainage should be reconsidered for patients undergoing DP.

Bile duct injuries (BDI) in the advanced laparoscopic cholecystectomy era.

BACKGROUND: Laparoscopic cholecystectomy is the most commonly performed laparoscopic procedure. It is superior in nearly every regard compared to open cholecystectomies. The one significant aspect where the laparoscopic approach is inferior regards the association with bile duct injuries (BDI). The BDI rate with laparoscopic cholecystectomy is approximately 0.5%; nearly triple the rate compared to the open approach. We propose that 0.5% BDI rate with the laparoscopic approach is no longer accurate. METHODS: The National Surgical Quality Improvement Program (NSQIP) registry was retrospectively reviewed. All laparoscopic cholecystectomies performed between 2012 and 2016 were extracted. A total of 217,774 cases meeting inclusion criteria were analyzed. The primary data points were the overall BDI incidence rate and time of diagnosis. BDI were identified by ICD-9 and ICD-10 codes. Secondary data points were variables associated with BDI. RESULTS: The BDI rate was 0.19%. 77% of cases were diagnosed after the index surgical admission. Intra-operative cholangiography (IOC) use was associated with a higher BDI rate and higher identification rate of a BDI intraoperatively (P value < 0.0001). Resident teaching cases were protective with a RR score of 0.56 (P value < 0.0001). The presence of cholecystitis increased the risk of a BDI with a RR score of 1.20 (P value < 0.0001). There was a low conversion rate of 0.04% however converted cases had a nearly hundredfold increase in BDI at 15% (P value < 0.0001). CONCLUSIONS: The performance of laparoscopic cholecystectomies in North America is no longer associated with higher BDI rates compared to open. IOC use still is not protective against BDI, and cholecystitis continues to be a risk factor for BDI. When a cholecystectomy requires conversion from a laparoscopic to an open approach the BDI increases a hundredfold; which may raise the concern if this approach is still a safe bailout method for a difficult laparoscopic dissection.

Improved hemostasis with major hepatic resection in the current surgical era.

BACKGROUND: Major hepatic resection, predominantly performed for oncologic intent, is a complex procedure with the potential for severe intraoperative hemorrhage. The current surgical era has the ability to improve hemostasis throughout the performance of major hepatic resections which decreases blood transfusions and the detrimental effects associated with transfusion. We evaluated hemostasis and outcomes in the current surgical era of performing hepatic resections. METHODS: Utilizing the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database all major hepatic resections performed between 2012 and 2016 were analyzed in regards to hemostasis. Hemostasis was evaluated by the need for and magnitude of blood transfusions. Additional perioperative variables (including operative time, length of hospital stay, and mortality rates) were analyzed to assess for outcomes with hemostasis. The NSQIP results were compared to previous publications involving major hepatic resections to detect improvement in hemostasis and outcomes in the current surgical era. RESULTS: A total of 22777 major hepatic resections met the inclusion criteria for analysis in the NSQIP database. An additional 21198 cases were compiled within the selected publications for comparative analysis. The transfusion rate in the current surgical era was 13.3% versus 38.7% in the previous era (P = 0.0001). When a transfusion was required in the current surgical era there was a two-fold reduction in the number of units transfused (1.5 U vs. 3.8 U, P = 0.0001). Statistically significant improvements in operative time and length of hospital stay were presented within the current surgical era (P = 0.0001). When a transfusion was required there was an increased relative risk score of 7 for mortality (4.9% vs. 0.7%, P = 0.0001), however, improvement in mortality rates did not reach statistical significance across surgical eras (1.3% vs. 4.0%, P = 0.0001). CONCLUSIONS: The conduction of major hepatic resection in the current surgical era is more hemostatic. Correlated with improved hemostasis are better outcomes for both clinical and financial endpoints. These findings should encourage continued and increased performance of major hepatic resections.