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.

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.

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.

A possible role for ketorolac in the management of increased biliary drain output.

Percutaneous transhepatic biliary drainage is used to achieve biliary decompression in jaundiced patients with biliary obstruction. High drain output >2000 mL/day is rare, and can cause dehydration and electrolyte derangements, without effective treatments. We present the first patient, to our knowledge, who reacted to the use of the analgesic ketorolac with progressive reduction in biliary output, in the setting of malignant biliary obstruction from duodenal adenocarcinoma.

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.

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.

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.

Adjuvant Chemotherapy Is Not Guided by Pathologic Treatment Effect After Neoadjuvant Chemotherapy in Pancreatic Cancer.

OBJECTIVES: Currently, there is no guidance for optimal adjuvant chemotherapy selection after pancreatectomy with a partial or poor response to neoadjuvant therapy. This study seeks to describe an institution's practice patterns of adjuvant chemotherapy selection after neoadjuvant therapy. METHODS: Patients at a single institution receiving neoadjuvant chemotherapy followed by pancreatectomy for pancreatic cancer were reviewed. Patients enrolled in trials or without follow-up were excluded. Types of chemotherapy, the College of American Pathologists pathologic tumor response, and medical oncology plans were recorded. RESULTS: Forty-one patients met inclusion criteria. Pathologic review of treatment effect demonstrated that 3 patients (7.3%) had complete pathologic response, 3 (7.3%) had near complete pathologic response, 16 (39%) had partial response, and 14 (34.1%) had poor/no response to neoadjuvant chemotherapy. Fourteen of the 30 patients with partial or poor response (46.7%) received an alternate adjuvant regimen. Pathologic response to neoadjuvant chemotherapy specifically guided therapy in 11 (30.5%) patients. CONCLUSIONS: Despite 73.1% of patients with partial or poor response to neoadjuvant chemotherapy, only 46.7% received a different adjuvant regimen. Medical oncologists infrequently considered treatment effect when choosing adjuvant therapy. Pathologic response to neoadjuvant chemotherapy should be considered when selecting adjuvant chemotherapy.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

BACKGROUND: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

The role of molecular biomarkers in outcomes and patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal metastases of colorectal (CRC) origin. The impact of different biomarkers in predicting recurrence after CRS/HIPEC is unclear. METHODS: Retrospective review of patients who underwent CRS/HIPEC for PC of CRC origin from 03/2007-08/2017. Molecular profile of the primary tumor was obtained from pathology reports, whenever available. RESULTS: Overall, 100 patients underwent CRS/HIPEC for peritoneal metastases of CRC origin. Most patients presented high grade tumor histology (G2/G3, n = 97, 97%), and a majority showed mucinous features (n = 61, 61%). At a median follow-up of 18 months, median DFS for the overall population was 13 months (95% CI 9.6, 16.4). Data reporting at least one mutational analysis was available in 64 patients. Microsatellite stability was detected in 42/50 (84%) patients, mKRAS in 25/51 (49%), and mBRAF in 5/35 (14.3%). On Kaplan-Meier analysis, BRAF was the only mutation associated with poor DFS (16 months, CI 95% 11.7-43.3 vs. 7 months, CI 95% 2.1-11.9, p = .008). On multivariate analysis, mBRAF independently predicted earlier recurrence (p = .032). CONCLUSIONS: In this analysis, mBRAF was independently associated with earlier recurrence in patients undergoing CRS/HIPEC for CRC, leading to dismal median DFS (7 months). Strict patient selection is advisable in these patients.

The significance of anatomic tumor location in gallbladder cancer.

BACKGROUND AND OBJECTIVES: Current management guidelines recognize the impact of hepatic versus peritoneal sided gallbladder cancers (GBC) on survival. However, no data exist regarding the significance of anatomic tumor location within the gallbladder. METHODS: We retrospectively analyzed all GBC that underwent surgical resection with curative intent in our health system from 2007 to 2017. We evaluated the effect of anatomic pathologic tumor location (fundus/body, neck, and multifocal) on clinicopathologic, perioperative, and oncologic outcomes. RESULTS: About 97 patients met criteria; 63% fundus/body, 22% multifocal, and 15% neck. Compared with fundus/body, neck tumors more frequently presented with preoperative jaundice (53% vs. 13%, p < .001), were smaller (20 mm vs. 30 mm, p = .068) and had significantly more biliary tree invasion (33% vs. 13%, p = .030) on histopathology. Although tumor characteristics (pTNM stage, liver invasion, lymphovascular invasion, prognostic nutritional index, and grade) were similar, neck tumors had significantly higher rates of R0 resection (53% vs. 11%, p < .001). Rates of adjuvant therapy were similar. Median PFS was similar between cohorts (p = .356). However, median overall survival (OS) was significantly shorter in neck (21 months) than fundus/body tumors (NR > 109 months), p = .015. CONCLUSIONS: Neck tumors were rare, small and more likely to result in jaundice secondary to biliary tree invasion. Despite higher R0 resection rates, these tumors had significantly worse OS.

Adeno-squamous and squamous cell carcinoma of the gallbladder: The importance of histology in surgical management.

BACKGROUND: Although gallbladder adenocarcinoma (AC) is potentially curable with resection, outcomes of squamous histologies are poorly described. METHODS: We retrospectively analyzed all gallbladder cancers which underwent resection-for-cure in our health system from 2007 to 2017. We compared outcomes of AC to adeno-squamous (ASC)/squamous (SC) histologies. RESULTS: 91 patients met criteria; 76 AC, 15 ASC/SC. Compared to AC, ASC/SC tumors were larger (58 vs. 28 mm), with more frequent liver invasion (73% vs. 37%), pN+ (60% vs. 32%), higher stage (III/IV 73% vs. 52%), and displayed more LVI (60% vs. 36%), p < 0.05. For stage III/IV disease, provided R0 was achieved, survival was durable and similar for ASC/SC and AC (OS median 28mo ASC/SC vs. 25mo AC, p = 0.132; PFS median 21mo ASC/SC vs. 13mo AC, p = 0.206). Pure SC had considerably poorer median OS (<5mo) than ASC (23mo) and AC (28mo). DISCUSSION: Squamous variants of gallbladder cancer confer aggressive and advanced disease and often require more radical resections to achieve R0. Durable survival is possible in ASC provided R0 is achieved. Pure SC has dismal survival even with R0 resection.

The importance of primary tumor origin in gastrointestinal malignancies undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Appendiceal and colorectal cancers with peritoneal carcinomatosis (PC) can derive benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, its role in gastric and small bowel malignancies remains undefined. METHODS: We retrospectively analyzed 251 gastrointestinal adenocarcinomas with PC which underwent CRS/HIPEC at our institution from 2007 to 2017. We compared outcomes of gastric, small bowel, appendiceal, and colorectal cohorts. RESULTS: Thirty-one gastric, 8 small bowel, 91 appendiceal, and 121 colorectal cohorts were included. More gastric cancers (90%) received neoadjuvant chemotherapy than any other cohort, p = 0.002. Although colorectal had the lowest peritoneal cancer index (PCI) (9) and appendiceal the highest (16), all cohorts underwent similar rates of organ resection and complete cytoreduction. Length of stay (p = 0.005) and major perioperative morbidity (Clavien III/IV, p = 0.011) were significantly higher in gastric and small bowel. Median overall survival (OS, p < 0.001) was significantly shorter in gastric (13 months) and small bowel (9 months) than in appendiceal (33 months) and colorectal (42 months) cohorts. On multivariate analysis, complete cytoreduction and PCI score were significant predictors of OS, p < 0.05. CONCLUSIONS: Primary tumor origin significantly affects outcomes after CRS/HIPEC for gastrointestinal malignancies. Though there was a survival benefit in appendiceal and colorectal, gastric and small bowel survival was comparable to systemic chemotherapy.

Distal pancreatectomy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: Identifying risk and improving patient selection.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become a principal tool in the management of peritoneal carcinomatosis (PC), but inclusion of pancreatic resection to obtain optimal debulking remains controversial. METHODS: We performed a retrospective review of 419 patients with PC who underwent CRS/HIPEC. The patients were divided into two cohorts, those with distal pancreatectomy (DP) and those without (NP), and morbidity and survival outcomes were compared. RESULTS: The DP cohort (n = 37) and the NP cohort (n = 371) had similar clinicopathologic characteristics (age, p = 0.596; gender, p = 0.328; ASA, p = 0.072). Operative time, number of organs resected, and EBL were greater in the DP cohort (<0.0001). A complete cytoreduction was achieved in 90% of the NP cohort versus 69% of the DP cohort (p = 0.0004). Major perioperative morbidity was more common in those with pancreatic resection (41% vs 19%, p = 0.002). However, there was no significant difference in 90-day mortality or overall survival. CONCLUSION: Achieving complete cytoreduction is critical to improving long term outcomes for patients with PC. Although pancreatic resections are associated with higher morbidity, short-term survival is not impacted adversely. Pancreatic involvement should not be a strict exclusion criterion for CRS/HIPEC, but patients need to be selected carefully, with close attention to disease burden prior to proceeding.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies?

BACKGROUND: Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies: hepatocellular carcinoma 11 months with sorafenib, and pancreaticobiliary 9-14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. METHODS: We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007 to 2017 and analyzed perioperative and oncologic outcomes. RESULTS: Seventeen patients were included: 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). Peritoneal cancer index, number of organs resected, completeness of cytoreduction, and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%, p = 0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months, p = 0.206) with 59% 3-year overall survival (vs. 0% cholangiocarcinoma, 0% gallbladder, 0% pancreatic). CONCLUSIONS: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.

Improved Survival with Experience: A 10-Year Learning Curve in Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an aggressive locoregional treatment for peritoneal carcinomatosis (PC). Studies demonstrate improved perioperative and oncologic outcomes at high-volume centers. METHODS: This study retrospectively analyzed all patients with PC from various malignancies who underwent attempted CRS/HIPEC at the authors' institution from 2007 to 2017. Clinicopathologic, perioperative, and oncologic outcomes of early (2007-2012) and late (2012-2017) experience were compared, and multivariate analyses for factors predictive of perioperative and oncologic outcomes were performed. RESULTS: The study enrolled 388 patients (157 early and 231 late). The late experience contained more appendiceal low-grade mucinous neoplasms (LGMNs; 21% vs 9%) and had a lower Peritoneal Cancer Index (PCI; 10 vs 16). Moreover, achieving a similar rate of CC-0/1 required fewer organ resections, involved shorter operations (298 vs 347 min), and had lower estimated blood loss (EBL) (400 vs 200 ml) (p < 0.05). More procedures were aborted (20% vs 3%; p < 0.01). The late experience had fewer ICU admissions (13% vs. 55%) and a lower perioperative mortality rate (0% vs 3%) (p < 0.05). In the multivariate analyses, PCI and number of organ resections were independent predictors of multiple perioperative outcomes [EBL, operating room time, intensive care unit (ICU) admission, ICU length of stay (LOS), overall LOS]. Survival was significantly longer in the late cohort (median overall survival: NR vs 31 months; progression-free survival: 22 vs 11 months; p < 0.01), even after control for tumor histology. CONCLUSIONS: At the authors' high-volume center, with increased surgeon and institutional experience over time, perioperative and oncologic outcomes have improved significantly for patients undergoing CRS/HIPEC for PC.

Surveillance of Low-Grade Appendiceal Mucinous Neoplasms With Peritoneal Metastases After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Are 5 Years Enough? A Multisite Experience.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMNs) are tumors that often present with widespread mucin in the peritoneal cavity (pseudomyxoma peritonei [PMP]). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment, but no published recommendations exist regarding surveillance. METHODS: Data from prospective databases of patients who underwent CRS-HIPEC from 2001 to 2017 at two high-volume institutions were retrospectively analyzed. Patients who underwent complete CRS-HIPEC for PMP secondary to LAMN were included in the analysis. Pathologic examination confirmed the diagnosis of LAMN. Cases of mucinous adenocarcinomas and neuroendocrine tumors (goblet cell carcinoids) were excluded. RESULTS: The study enrolled 156 patients. The median peritoneal cancer index (PCI) was 18 (interquartile range IQR1-3, 12-23), and 125 patients (80.1%) had a CC0 cytoreduction. According to American Joint Committee on Cancer (AJCC) grading, 152 patients (97.4%) presented with acellular mucin or G1 implants, 2 patients (1.3%) presented with G2 disease, and 2 patients (1.3%) presented with G3 disease. During the follow-up period (median, 45 months; IQR1-3 23-76 months), 23 patients (14.7%) experienced recurrence. All the recurrences were peritoneal and occurred within 5 years. The 1-, 3-, and 5-year disease-free survival (DFS) rates were respectively 95.5%, 83.4%, and 78.3%. Univariate Cox regression analysis showed that higher PCI scores (p < 0.001), a CC1 cytoreduction (p = 0.005), and higher preoperative levels of carcinoembryonic antigen (CEA) (p = 0.012) and CA-125 (p = 0.032) correlated with a shorter DFS. Only higher PCI scores independently predicted earlier recurrences (p < 0.001). CONCLUSION: Most patients had recurrence within 3 years after CRS-HIPEC, and none after 5 years. High PCI was the only independently significant variable. The study findings support intensive surveillance (every 3-6 months) with tumor markers and imaging methods during the first 3 years, and annual surveillance thereafter, with follow-up assessment after 5 years yielding limited benefit.