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.

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 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.

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.

African Immigrants in New York City with Hepatitis B-Related Hepatocellular Carcinoma Demonstrate High Morbidity and Mortality.

Guidelines recommend hepatitis B (HBV) testing in individuals from endemic areas, and if positive, screening for hepatocellular carcinoma (HCC). While screening programs are well established in the Asian immigrant population in New York City (NYC), less is known about the characteristics of HBV/HCC among the African immigrant community. A retrospective review was performed of HCC cases from 2005 to 2018 at our institution. Country of origin was not documented in the electronic medical record; therefore, African immigrant status was approximated using self-identified race/ethnicity, positive HBV status, and an online registry to determine country of origin based on last name. Surnames with the greatest prevalence or density in an African country were considered. Among 4400 patients with HCC, 472 identified as non-Hispanic Black; of these, 86 were HBV+. Based on surname, it was estimated that 33 individuals were likely immigrants from Africa. In this group, median age of HCC diagnosis was 48 years (IQR 43-55). In patients with an available date of HBV diagnosis (n = 24), 17 (71%) were unaware of their HBV status when they presented with HCC. Zero patients were diagnosed with HCC through routine screening, most patients (66%) were diagnosed upon imaging evaluation of symptoms. Twelve patients (36%) underwent resection or transplantation; the remaining 64% were ineligible for surgical treatment. Of the 26 patients with follow-up data, 18 (69%) died of disease or were critically ill at last encounter, and of these, 14 (77%) died within 1 year of HCC diagnosis. In conclusion, African immigrants in NYC with HBV/HCC are at high risk of HCC related mortality at a young age. Most were unaware of their hepatitis status at the time of HCC diagnosis. No patients were enrolled in routine HCC screening; the majority were diagnosed based on imaging obtained for symptoms. Most individuals presented with inoperable disease, and the majority died within months of diagnosis. Awareness of these findings may help healthcare providers improve patient outcomes.

Triple threat: pancreatic cystic lesion presenting with spontaneous hemorrhage is found to harbor three distinct neoplasms.

BACKGROUND: Pancreatic serous cystadenoma (SCA) is a benign, cystic lesion with an indolent growth pattern. Complications such as spontaneous hemorrhage or malignant transformation from SCA are extremely rare. Our case report describes an unusual presentation of a patient with a previously diagnosed SCA, made unique by the presence of three separate neoplasms in the final specimen. CASE PRESENTATION: A 74-year-old male with a previous diagnosis of SCA presented emergently with epigastric pain and non-bilious vomiting. Laboratory results were notable for a hemoglobin of 8.3 g/dl. CT scan of the abdomen demonstrated a complex, solid-cystic mass in the pancreatic head with a large hematoma and questionable focus of active hemorrhage. Surgical resection was recommended due to the risk of malignancy, possibility of re-bleeding, and symptoms of severe duodenal compression. Pancreaticoduodenectomy was performed, and final pathology demonstrated three separate neoplasms: serous cystadenoma, intraductal papillary mucinous neoplasm, and neuroendocrine tumor. CONCLUSION: While pancreatic SCA are benign tumors that can be observed safely in the majority of cases, surgical intervention is often indicated in patients with large, symptomatic cysts or when diagnosis is unclear. When undergoing surveillance, it is crucial for both the patient and the care team to be aware of the possibility of rare, but life-threatening complications, such as hemorrhage. Likewise, the possibility of misdiagnosis or concurrent neoplasia should be considered.