Prophylactic Cholecystectomy is Safe in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: While cholecystectomy is one of the most common operations performed in the United States, there is a continued debate regarding its prophylactic role in elective surgery. Particularly among patients with peritoneal carcinomatosis who undergo cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), further abdominal operations may pose increasing morbidity due to intraabdominal adhesions and potential recurrence. This bi-institutional retrospective study aims to assess postoperative morbidity associated with prophylactic cholecystectomy at the time of CRS-HIPEC. METHODS: We performed a bi-institutional retrospective analysis of 578 patients who underwent CRS-HIPEC from 2011 to 2021. Postoperative outcomes among patients who underwent prophylactic cholecystectomy at the time of CRS-HIPEC were compared to patients who did not, particularly rate of bile leak, hospital length of stay, rate of Clavien-Dindo classification morbidity grade III or greater, and number of hospital re-admissions within 30 days. RESULTS: Of the 535 patients available for analysis, 206 patients (38.3%) underwent a prophylactic cholecystectomy. Of the 3 bile leaks (1.5%) that occurred among patients who underwent prophylactic cholecystectomy, all 3 occurred in patients who underwent a concomitant liver resection. There were no significant differences in hospital length of stay, postoperative morbidity, and number of hospital re-admissions among patients who underwent prophylactic cholecystectomy compared to those who did not. CONCLUSION: Prophylactic cholecystectomy in patients undergoing CRS-HIPEC is not associated with increased morbidity or increased bile leak risk compared to historical data. While the benefits of prophylactic cholecystectomy are not yet elucidated, it may be considered to avoid potential future morbid operations for biliary disease.

Actual 5-Year Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis of Colorectal Origin.

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. METHODS: We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. RESULTS: A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. CONCLUSIONS: Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: Effects of postoperative fluids beyond the first 24 h.

BACKGROUND AND OBJECTIVES: There are no guidelines for intravenous fluid (IVF) administration after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study assessed rates of post-CRS/HIPEC morbidity according to perioperative IVF administration. METHODS: All patients undergoing CRS/HIPEC March 2007 to June 2018 were reviewed, recording clinicopathologic, operative, and postoperative variables. Patients were divided by peritoneal cancer index (PCI), comparing IVF volumes and types administered intraoperatively and during the first 72 h postoperatively. Optimal IVF rate cutoffs calculated using area under the receiver operating characteristic curves and Youden's index determined associations with complications. RESULTS: Overall, 185 patients underwent CRS/HIPEC, and 81 (51%) had low PCI (<10) and 77 (49%) had high PCI (≥10). In low-PCI patients, high IVF rates on postoperative days (POD) #0-2 were associated with higher overall complications: POD#0 (46% vs. 89%, p = 0.001), POD#1 (40% vs. 86%, p < 0.05), and POD#2 (42% vs. 72%, p < 0.05). High IVF rates were associated with respiratory distress (7% vs. 26%, p = 0.02) on POD#0, ileus (14% vs. 47%, p = 0.007) and intensive care unit stay (11% vs. 33%, p = 0.022) on POD#1, and ICU stay (8% vs. 33%, p = 0.003) on POD#2. CONCLUSIONS: For low PCI patients undergoing CRS/HIPEC, higher IVF rates were associated with postoperative complications. Post-CRS/HIPEC, IVF rates should be limited to prevent morbidity.

Major Postoperative Complications Limit Adjuvant Therapy Administration in Patients Undergoing Pancreatoduodenectomy for Distal Cholangiocarcinoma or Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Guidelines for perioperative systemic therapy administration in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are evolving. Decisions regarding adjuvant therapy are influenced by postoperative morbidity, which is common after pancreatoduodenectomy. We evaluated whether postoperative complications are associated with receipt of adjuvant therapy after pancreatoduodenectomy. METHODS: A retrospective analysis of patients undergoing pancreatoduodenectomy for PDAC or dCCA from 2015 to 2020 was conducted. Demographic, clinicopathologic, and postoperative variables were analyzed. RESULTS: Overall, 186 patients were included-145 with PDAC and 41 with dCCA. Postoperative complication rates were similar for both pathologies (61% and 66% for PDAC and dCCA, respectively). Major postoperative complications (MPCs), defined as Clavien-Dindo >3, occurred in 15% and 24% of PDAC and dCCA patients, respectively. Patients with MPCs received lower rates of adjuvant therapy administration, irrespective of primary tumor (PDAC: 21 vs. 72%, p = 0.008; dCCA: 20 vs. 58%, p = 0.065). Recurrence-free survival (RFS) was worse for patients with PDAC who experienced an MPC [8 months (interquartile range [IQR] 1-15) vs. 23 months (IQR 19-27), p < 0.001] or who did not receive any perioperative systemic therapy [11 months (IQR 7-15) vs. 23 months (IQR 18-29), p = 0.038]. In patients with dCCA, 1-year RFS was worse for patients who did not receive adjuvant therapy (55 vs. 77%, p = 0.038). CONCLUSION: Patients who underwent pancreatoduodenectomy for either PDAC or dCCA and who experienced an MPC had lower rates of adjuvant therapy and worse RFS, suggesting that clinicians adopt a standard neoadjuvant systemic therapy strategy in patients with PDAC. Our results propose a paradigm shift towards preoperative systemic therapy in patients with dCCA.

Perineural Invasion of Pancreatic Ductal Adenocarcinoma is Associated with Early Recurrence after Neoadjuvant Therapy Followed by Resection.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly utilized in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, there are limited data on risk factors and patterns of recurrence after surgical resection. This study aimed to analyze timing and recurrence patterns of PDAC after NAT followed by curative resection. METHODS: The medical charts of patients with PDAC treated with NAT followed by curative-intent surgical resection at a single health system from January 1, 2012 to January 1, 2020 were retrospectively reviewed. Early recurrence was defined as recurrence within 12 months of surgical resection. RESULTS: 91 patients were included and median follow up was 20.1 months. Recurrence occurred in 50 (55%) patients, with median recurrence free survival (RFS) of 11.9 months. Overall, 18 (36%) patients had local and 32 (64%) had distant recurrences. Median RFS and overall survival (OS) between local and distant recurrence were similar. Perineural invasion (PNI) and the presence of a T2 + tumor was significantly higher in recurrence group than in no recurrence group. PNI was a significant risk factor for early recurrence. CONCLUSION: After NAT and surgical resection of PDAC, disease recurrence was common, with distant metastasis being the most common. PNI was significantly higher in the recurrence group.

T1 Gastric Cancer Is Associated With a High Incidence of Regional Lymph Node Metastases.

INTRODUCTION: Early stage gastric cancer, particularly T1 disease, is associated with high recurrence-free and overall survival rates following resection with curative intent. However, rare cases of T1 gastric cancer have nodal metastasis and this is associated with poor outcomes. METHODS: Data from gastric cancer patients treated with surgical resection and D2 lymph node (LN) dissection at a single tertiary care institution from 2010 to 2020 were analyzed. Patients with early stage (T1) tumors were assessed in detail to identify variables associated with regional LN metastasis including histologic differentiation, signet ring cells, demographics, smoking history, neoadjuvant therapy, and clinical staging by endoscopic ultrasound (EUS). We used standard statistical techniques including Mann-Whitney U and Chi-squared tests. RESULTS: Of 426 patients undergoing surgery for gastric cancer, 34% (n = 146) were diagnosed with T1 disease on surgical pathology. Among 146 T1 (T1a, T1b) gastric cancers, 24 patients [(17%) T1a (n = 4), T1b (n = 20)] had histologically confirmed regional LN metastases. The age at diagnosis ranged between 19 and 91 y and 54.8% were male. Prior smoking status was not associated with nodal positivity (P = 0.650). Of the 24 patients with positive LN on final pathology, seven patients received neoadjuvant chemotherapy. EUS was performed on 98 (67%) of the 146 T1 patients. Of these patients, 12 (13.2%) had positive LN on final pathology; however, none (0/12) were detected on preoperative EUS. There was no association between node status on EUS and node status on final pathology (P = 0.113). The sensitivity of EUS for N status was 0%, specificity was 84.4%, negative predictive value was 82.2% and positive predictive value was 0%. Signet ring cells were identified in 42% of node negative T1 tumors and 64% of node positive T1 tumors (P = 0.063). For LN positive cases on surgical pathology, 37.5% had poor differentiation, 42% had lymphovascular invasion, and regional nodal metastases were associated with increasing T stage (P = 0.003). CONCLUSIONS: T1 gastric cancer is associated with a substantial risk (17%) of regional LN metastasis, when pathologically staged following surgical resection and D2 lymphadenectomy. Clinically staged N+ disease by EUS was not significantly associated with pathologically staged N+ disease in these patients.

FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis: a prospective multireader pilot study.

PURPOSE: To assess the diagnostic performance of FDG-PET/MRI for the preoperative diagnosis and staging of peritoneal carcinomatosis (PC) using surgical Sugarbaker's PC index (PCI) as the reference in a multireader pilot study. METHODS: Fourteen adult patients (M/F: 3/11, mean age: 57 ± 12 year) with PC were prospectively included in this single-center study. Patients underwent FDG-PET/MRI prior to surgery (mean delay: 14 d, range: 1-63 d). Images were reviewed independently by 2 abdominal radiologists and 2 nuclear medicine physicians. The radiologists assessed contrast-enhanced abdominal MR images, while the nuclear medicine physicians assessed PET images fused with T2-weighted images. The abdomen was divided in 13 regions, scored from 0 to 3. A hybrid FDG-PET/MRI radiological PCI was created by combining the study data. Radiological PCI was compared to the surgical PCI on a per-patient and per-region basis. Inter-reader agreement was evaluated. RESULTS: Mean surgical PCI was 10 ± 8 (range: 0-24). Inter-reader agreement was almost perfect for all sets for radiologic PCI (Kappa: 0.81-0.98). PCI scores for all reading sets significantly correlated with the surgical PCI score (r range: 0.57-0.74, p range: < 0.001-0.003). Pooled per-patient sensitivity, specificity, and accuracy were 75%/50%/71.4% for MRI, 66.7%/50%/64.3% for FDG-PET, and 91.7%/50%/85.7% for FDG-PET/MRI, without significant difference (p value range 0.13-1). FDG-PET/MRI achieved 100% sensitivity and 100% specificity for a cutoff PCI of 20. Per-region sensitivity and accuracy were lower: 37%/61.8% for MRI, 17.8%/64.3% for FDG-PET, and 52.7%/60.4% for FDG-PET/MRI, with significantly higher sensitivity for FDG-PET/MRI. Per-region specificity was higher for FDG-PET (95%) compared to MRI (78.4%) and FDG-PET/MRI (66.5%). CONCLUSION: FDG-PET/MRI achieved an excellent diagnostic accuracy per-patient and weaker performance per-region for detection of PC. The added value of PET/MRI compared to MRI and FDG-PET remains to be determined.

A total neoadjuvant chemotherapy approach is associated with improved recurrence-free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC.

BACKGROUND: The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. RESULTS: A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. CONCLUSION: In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases.

INTRODUCTION: Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. METHODS: We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. RESULTS: A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. CONCLUSIONS: In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

Postoperative Respiratory Failure Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy is Associated with Volume of Intraoperative Crystalloid Administration and Worse Survival.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased morbidity after surgery. This retrospective study explores preoperative and perioperative risk factors associated with PRF in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and the resultant impact on survival. METHODS: We identified all patients who underwent CRS/HIPEC at our institution between 2007 and 2017. PRF was defined as mechanical ventilation for more than 48 h after surgery or reintubation not related to an additional procedure within the first 30 days postoperatively. The relationship between clinicopathologic variables and PRF was examined using Kaplan-Meier log-rank survival analysis and multivariable Cox regression models with 90-day, 1-year and 5-year overall survival (OS). RESULTS: Overall, 314 patients underwent CRS/HIPEC, of whom 24 patients (7.6%) developed PRF. On univariable analysis, chronic obstructive pulmonary disease (COPD) was the only preoperative risk factor associated with PRF (p = 0.049). Of the intraoperative risk factors, diaphragmatic resection (p = 0.008), Peritoneal Cancer Index (PCI) > 20 (p < 0.001), and volume of intraoperative crystalloid (p < 0.001) were all associated with PRF. On multivariable Cox regression, only intraoperative crystalloid was significantly associated with PRF (p < 0.001), with a volume above 5.3 L (area under the curve [AUC] 0.77) having a high predictive accuracy for PRF. Five-year OS was significantly decreased in patients with PRF (30.2% vs. 52.6%, hazard ratio 2.6, 95% confidence interval 1.5-4.4; p < 0.001). CONCLUSIONS: Liberal intraoperative crystalloid volume resuscitation is a potential independent, modifiable intraoperative risk factor for PRF following CRS/HIPEC that may contribute to decreased long-term OS.

Hyperthermic intraperitoneal chemotherapy does not increase risk of major complication or failure to rescue in cytoreductive surgery.

INTRODUCTION: Failure to rescue (FTR) is defined as death after a major complication. We evaluated FTR after cytoreductive surgery (CRS) with and without hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The ACS NSQIP database 2005-2018 was reviewed for all cases of CRS. Propensity score matching was used to compare outcomes between those undergoing CRS alone and those undergoing CRS/HIPEC. Patients were matched on age, sex, ascites, diabetes, hypertension and resection of liver, pancreas, colon/rectum, diaphragm, stomach, small bowel, and/or spleen. RESULTS: Thirty nine thousand one hundred and twenty-six patients underwent CRS; 38,387 underwent CRS alone; 739 underwent CRS/HIPEC. After matching there were 726 patients in each arm. Patients undergoing CRS/HIPEC had higher risk of reintubation (25 [3.4%] vs. 13 [1.8%] p = 0.049), urinary tract infection UTI (44 [6.1%] vs. 25 [3.4%] p = 0.019) and sepsis (73 [10.1%] vs. 44 [6.1%] p = 0.005). Patients in the CRS arm required more transfusions (229 [31.5%] vs. 176 [24.2%] p = 0.002). There was no significant difference in FTR between the CRS and CRS/HIPEC groups (11 [4.0%] vs. 6 [2.3%] p = 0.258), nor in the pooled incidence of major complications (275 [37.9%] vs. 262 [36.1%] p = 0.48). CONCLUSION: CRS/HIPEC is associated with increased rates of reintubation, UTI, and sepsis while CRS alone was associated with increased transfusion. However, the addition HIPEC to CRS did not increase the risk of pooled major complication or FTR.

Hypophosphatemia Is Associated With Postoperative Morbidity After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: A Retrospective Study.

INTRODUCTION: Hypophosphatemia following surgery is associated with a higher rate of postoperative complications; however, the significance of postoperative hypophosphatemia after cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. METHODS: A prospectively maintained database was queried for all patients who underwent CRS/HIPEC for any histology at the Mount Sinai Health System. The perioperative serum phosphate levels, postoperative complications, and comorbidities were compared between patients with or without major complications. RESULTS: From 2007 to 2018, 327 patients underwent CRS/HIPEC. Most of the patients had low phosphate levels on postoperative day (POD) 2, reaching a median nadir of 2.3 mg/dL on POD 3. Patients with major complications had significantly lower levels of serum phosphate on POD 5-7 compared with patients without complications, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.4) versus 2.7 mg/dL, (IQR 2.3-3), P < 0.01. Hypophosphatemia on POD 5-7 was also more frequent in patients who developed an anastomotic leak, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.6) versus 2.8 mg/dL (IQR 2.2-3.2), P = 0.001. On multivariate analysis, the number of organs resected at surgery, diaphragm resection, postoperative intensive care unit stay, and serum phosphate level <2.4 mg/dL on POD 5-7 were independently associated with a major complication after CRS/HIPEC. CONCLUSIONS: Following CRS/HIPEC, POD 5-7 hypophosphatemia is associated with severe postoperative complications and anastomotic leak.

Gallbladder Cancer: A Single-Institution 10-Year Experience-Analysis of Adenocarcinoma Subtypes and Tumors Arising from Intracholecystic Papillary Neoplasms.

BACKGROUND: Gallbladder cancer accounts for 1.2% of global cancer diagnoses. Literature on biliary-type adenocarcinoma (BTA), and specifically carcinoma arising from intracholecystic papillary-tubular neoplasms (ICPNs), is limited. This study describes a retrospective, single-institution experience with gallbladder cancer, focusing on histological subtypes and prognosis. METHODS: A retrospective review was performed of patients who underwent cholecystectomy for a malignant neoplasm of the gallbladder between 2007 and 2017. Demographic, clinicopathologic, and operative variables, as well as survival outcomes, were analyzed. RESULTS: From a total of 145 patients, BTAs were most common (93, 64%). Compared with non-BTAs, BTAs were diagnosed at a lower American Joint Committee on Cancer stage (p = 0.045) and demonstrated longer median recurrence-free survival (38 vs. 16 months, p = 0.014; median follow-up 36 months). Tumors arising from ICPNs (18, 12%) were more commonly associated with BTA (14 cases). Compared with BTAs not associated with ICPNs (29 patients), associated cases demonstrated lower pathologic stage (p = 0.006) and lower rates of liver and perineural invasion (0% vs. 49% and 14% vs. 48%, respectively; p < 0.05). Cumulative 5-year survival probability was higher for patients with gallbladder neoplasm of any subtype associated with ICPNs compared with those that were not associated with ICPNs (54% vs. 41%, p = 0.019; median follow-up 23 months). This difference was also significant when comparing BTAs associated with ICPNs and non-associated cases (63% vs. 52%, p = 0.005). CONCLUSIONS: This study demonstrated unique pathological and prognostic features of BTAs and of carcinomas arising from ICPNs. Histopathological variance may implicate prognosis and may be used to better guide clinical decision making in the treatment of these patients.

Surgical management of pancreatic cancer liver oligometastases.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, which commonly metastasizes to the liver. The current standard of care for metastatic PDAC is systemic chemotherapy, however there are limited emerging data regarding surgical resection of pancreatic oligometastases in select patients. Here we review the literature addressing resection of PDAC liver oligometastases.

Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial.

BACKGROUND: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma. METHODS: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing. FINDINGS: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks. INTERPRETATION: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma. FUNDING: Regeneron Pharmaceuticals.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with improved perioperative outcomes: a single-center early experience propensity-matched analysis.

INTRODUCTION: The role of laparoscopy in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not well established. Herein, we describe our early experience of laparoscopic CRS/HIPEC in patients with low-volume peritoneal disease compared to patients who underwent open CRS/HIPEC during the same time period. METHODS: Using a prospectively maintained database, patients who underwent laparoscopic CRS/HIPEC were compared to a control cohort of patients who underwent open CRS/HIPEC, matched for peritoneal carcinomatosis index (PCI), completeness of cytoreduction, and tumor histology. RESULTS: Between 2008 and 2017, 16 patients underwent laparoscopic CRS/HIPEC and were compared to a matched control cohort of 32 patients who underwent open CRS/HIPEC. Clinical and demographic data were similar between the groups. PCI, number of resected organs, and optimal cytoreduction rates were comparable. Patients who underwent laparoscopic experienced a lower estimated blood loss, (median, [IQR 1-3]); 150 mL, [50-300] vs. 100 mL, [50-125], p = 0.04, shorter length of stay (median [IQR 1-3]; 4 days [3-6] vs. 6 days [5-8], p < 0.01, and a lower 30-day complication rate (6.3% vs. 56.3%, p < 0.01). There was no difference in progression-free survival (p = 0.577) and overall survival (p = 0.472) between the groups. CONCLUSIONS: This preliminary study demonstrates that laparoscopic CRS/HIPEC is feasible and safe for curative treatment in selected patients with low tumor volume. Minimally invasive CRS/HIPEC is associated with fewer postoperative complications and shorter length of stay. There was no difference in long-term oncological outcomes between the groups.