Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.

INTRODUCTION: Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line. PATIENTS AND METHODS: PTOs were fabricated from tumor specimens obtained from patients with AC undergoing cytoreductive surgery with HIPEC. PTOs underwent HIPEC treatment with bromelain, cisplatin, and mitomycin C (MMC) at 37 °C and 42 °C with and without bromelain pretreatment. RESULTS: From October 2020 to May 2023, 16 specimens were collected from 13 patients with low-grade (12/16, 75%) and high-grade AC (4/16, 25%). The mucin-depleting effects of bromelain were most significant in combination with N-acetylcysteine (NAC) compared with bromelain (47% versus 10%, p = 0.0009) or NAC alone (47% versus 12.8%, p = 0.0027). Bromelain demonstrated > 31% organoid viability reduction at 60 min (p < 0.001) and > 66% in 48 h (p < 0.0001). Pretreatment with bromelain increased cytotoxicity of both cisplatin and MMC HIPEC conditions by 31.6% (p = 0.0001) and 35.5% (p = 0.0001), respectively. Ki67, CK20, and MUC2 expression decreased after bromelain treatment; while increased caspase 3/7 activity and decreased Bcl-2 (p = 0.009) and Bcl-xL (p = 0.01) suggest induction of apoptosis pathways. Furthermore, autophagy proteins LC3A/B I (p < 0.03) and II (p < 0.031) were increased; while ATG7 (p < 0.01), ATG 12 (p < 0.04), and Becline 1(p < 0.03), expression decreased in bromelain-treated PTOs. CONCLUSIONS: Bromelain demonstrates cytotoxicity and mucolytic activity against appendiceal cancer organoids. As a pretreatment agent, it potentiates the cytotoxicity of multiple HIPEC regimens, potentially mediated through programmed cell death and autophagy.

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.

Patient-Specific Sarcoma Organoids for Personalized Translational Research: Unification of the Operating Room with Rare Cancer Research and Clinical Implications.

INTRODUCTION: Sarcoma clinical outcomes have been stagnant for decades due to heterogeneity of primaries, lack of comprehensive preclinical models, and rarity of disease. We hypothesized that engineering hydrogel-based sarcoma organoids directly from the patient without xenogeneic extracellular matrices (ECMs) or growth factors is routinely feasible and allows rare tumors to remain viable as avatars for personalized research. METHODS: Surgically resected sarcomas (angiosarcomas, leiomyosarcoma, gastrointestinal stromal tumor, liposarcoma, myxofibrosarcoma, dermatofibrosarcoma protuberans [DFSP], and pleiomorphic abdominal sarcoma) were dissociated and incorporated into a hyaluronic acid and collagen-based ECM hydrogel and screened for chemotherapy efficacy. A subset of organoids was enriched with a patient-matched immune system for screening of immunotherapy efficacy (iPTOs). Response to treatment was assessed using LIVE/DEAD staining and metabolic assays. RESULTS: Sixteen sarcomas were biofabricated into three-dimensional (3D) patient-specific sarcoma organoids with a 100% success rate. Average time from organoid development to initiation of drug testing was 7 days. Enrichment of organoids with immune system components derived from either peripheral blood mononuclear cells or lymph node cells was performed in 10/16 (62.5%) patients; 4/12 (33%) organoids did not respond to chemotherapy, while response to immunotherapy was observed in 2/10 (20%) iPTOs. CONCLUSIONS: A large subset of sarcoma organoids does not exhibit response to chemotherapy or immunotherapy, as currently seen in clinical practice. Routine development of sarcoma hydrogel-based organoids directly from the operating room is a feasible platform, allowing for such rare tumors to remain viable for personalized translational research.

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).

Persistent opioid use after curative-intent hepatectomy for neoplastic disease.

BACKGROUND AND OBJECTIVES: This study analyzed persistent opioid use in opioid-naïve and nonopioid-naïve patients undergoing hepatectomy for neoplastic disease. METHODS: A retrospective review was performed of a prospective database using inclusion criteria of hepatectomy for neoplastic disease from October 2013 to December 2017. Prescription data were collected from the North Carolina Controlled Substance Reporting System. Persistent opioid use was defined as patients who continued filling opioid prescriptions 90 days to 1 year after surgery. Patients who did not receive opioid prescriptions between 12 months and 31 days before surgery were defined as naïve. RESULTS: The analysis included 75 surgeries on naïve and 58 surgeries on nonnaïve patients. 56% of naïve patients and 79% of nonnaïve patients developed persistent opioid use, respectively (p = .0056). Naïve patients received 2.24 ± 4.30 MMEs/day, while nonnaïve patients received 5.50 ± 5.98 MMEs/day during Postoperative days 90-360 (95% CI, 1.41-5.10; p < .001). Naïve patients with a lower Preoperative ECOG score were more likely to develop persistent opioid use (OR, 0.45; 95% CI, 0.21-0.99; p = .048). CONCLUSION: More than half of naïve patients undergoing hepatectomy developed persistent opioid use within the first year, though significantly less than nonnaïve patients. Improved performance status was associated with an increased risk of persistent opioid use in naïve patients.

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.