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.

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.

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.

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.

Diaphragmatic Peritoneal Stripping Versus Full-Thickness Resection in CRS/HIPEC: Is There a Difference?

BACKGROUND: Pleural recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare and poorly delineated. Specifically, data are limited on the effect that diaphragmatic peritoneal stripping versus full-thickness resection has on the nature of ipsilateral pleural recurrence and postoperative morbidity. METHODS: Patients with peritoneal carcinomatosis who underwent CRS/HIPEC were included from a prospectively maintained database. The patients were divided into three cohorts based on surgical management of the diaphragm as follows: diaphragm-stripping (DS) cohort, full-thickness resection (FTR) cohort, and no diaphragm manipulation (ND) cohort. Postoperative morbidity and incidence of ipsilateral pleural recurrence were evaluated. All diaphragmatic defects were closed before abdominal chemoperfusion. RESULTS: The inclusion criteria were met by 409 CRS/HIPEC procedures: 66 in DS, 122 in FTR, and 238 in ND. Ipsilateral pleural recurrence rates did not differ significantly between the three cohorts (DS 6%, FTR 3%, ND 3%; p = 0.470). Postoperative respiratory complications and overall morbidity were significantly greater for the patients who underwent diaphragmatic disruption (stripping and/or resection) than for the patients who did not (p ≤ 0.0001), but the two groups did not differ in terms of 30-day mortality. However, comparison of FTR with DS showed no impact on major morbidity or pleural recurrence. CONCLUSION: Although patients undergoing surgical manipulation of the diaphragm during CRS/HIPEC experienced significantly greater morbidity, diaphragmatic stripping did not differ from full-thickness resection in terms of grades 3 and 4 complications or incidence of ipsilateral pleural recurrences. When deemed necessary to achieve complete cytoreduction, full-thickness diaphragmatic resection should be undertaken. In addition, the data support the observation that definitive repair of the diaphragmatic defect before abdominal chemoperfusion does not adversely influence ipsilateral pleural recurrence.

Staging gallbladder cancer with lymphadenectomy: the practical application of new AHPBA and AJCC guidelines.

BACKGROUND: Current guidelines recommend harvesting a total lymph node count (TLNC) ≥6 from portal lymphadenectomy in ≥pT1b gallbladder cancers (GBC) for accurate staging and prognostication. This study aimed to determine nodal yields from portal lymphadenectomy and identify measures to maximize TLNC. METHODS: We retrospectively reviewed all ≥pT1b GBC which underwent resection with curative intent including portal lymphadenectomy at our specialized HPB center from 2007 to 2017. We compared outcomes of TLNC < 6 and TLNC ≥ 6 cohorts and determined factors predictive of TLNC. RESULTS: Of 92 patients, 20% had a TLNC ≥ 6 (IQR 7-11) and 9% had no nodes found on pathology. Malignant lymphadenopathy was twice as common in TLNC ≥ 6 as TLNC < 6 (p = 0.003) most frequently from portal, cystic and pericholedochal stations. On logistic regression analysis, concomitant liver resection was an independent predictor of higher TLNC [4b/5 wedge resection (OR 0.166, CI 0.057-0.486, p = 0.001) extended hepatectomy (OR 0.065, CI 0.012-0.340, p = 0.001)]; biliary resection and en bloc adjacent organ resection were not. CONCLUSION: At our center, prior to current guidelines, a TLNC≥6 was not met in 80% undergoing portal lymphadenectomy for ≥ pT1b GBC. To increase nodal yield, future guidelines should consider including additional lymph node stations and incorporation of frozen section analysis.