The adverse characteristics of hepatocellular carcinoma in the non-cirrhotic liver disproportionately disadvantage Black patients.

BACKGROUND: Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria. METHODS: Demographic, imaging, laboratory, and pathology data of HCC patients at our institution, 2003-2018, were reviewed, retrospectively. Race/ethnicity were self-reported. Cirrhosis was defined as a Fibrosis-4 score ≥3.25. RESULTS: Compared to 1146 cirrhotic patients, 411 non-cirrhotic patients had larger tumors (median 4.7 cm vs. 3.1 cm, p < 0.01) and were less likely to be within Milan criteria (42.6% vs. 57.7%, p < 0.01). Among non-cirrhotic patients, Black patients had larger tumors (4.9 cm vs. 4.3 cm, p < 0.01) and a higher percentage of poorly differentiated tumors (39.4% vs. 23.1%, p = 0.02). Among cirrhotic patients, Black patients had larger tumors (3.3 cm vs. 3.0 cm, p = 0.03) and were less likely to be within Milan criteria (52.3% vs. 83.2%, p < 0.01). In multivariable analysis, lack of commercial insurance (OR 1.45 [CI 95% 1.19-1.83], p < 0.01), male sex (OR 1.34 [CI 95% 1.05-1.70], p < 0.01), absence of cirrhosis (OR 1.58 [CI 95% 1.27-1.98], p < 0.01) and Black race/ethnicity (OR 1.34 [CI 95% 1.09-1.66], p = 0.01) were associated with HCC beyond Milan criteria. Black patients had lower survival rates than other patients (p < 0.01). CONCLUSIONS: Non-cirrhotic patients had more advanced HCC than cirrhotic patients. Black patients (with or without cirrhosis) had more advanced HCC than comparable non-Black patients and higher mortality rates. Improved access to healthcare (commercial insurance) may increase early diagnosis (within Milan criteria) and reduce disparities.

Excision of malignant and pre-malignant rectal lesions by transanal endoscopic microsurgery in patients under 50 years of age.

BACKGROUND: The most common technique for treating benign and early malignant rectal lesions is transanal endoscopic microsurgery (TEM). Local excision is an acceptable technique for high-risk and elderly patients, but there are hardly any data regarding young patients. AIM: To describe TEM outcomes in patients under 50 years of age. METHODS: We collected demographic, clinical, and pathological data from all patients under the age of 50 years who underwent the TEM procedure at Hasharon Rabin Medical Center from January 2005 to December 2018. RESULTS: During the study period, a total of 26 patients under the age of 50 years underwent TEM procedures. Their mean age was 43.3 years. Eleven (42.0%) were male. The mean operative time was 67 min, and the mean tumor size was 2.39 cm, with a mean anal verge distance of 8.50 cm. No major intraoperative or postoperative complications were recorded. The median length of stay was 2 d. Seven (26.9%) lesions were adenomas with low-grade dysplasia, four (15.4%) were high-grade dysplasia adenomas, two were T1 carcinomas (7.8%), and three were T2 carcinomas (11.5%). No residual disease was found following endoscopic polypectomy in two patients (7.8%), but four (15.4%) had other pathologies. Surgical margins were negative in all cases. Local recurrence was detected in one patient 33 mo following surgery. CONCLUSION: Among young adult patients, TEM for benign rectal lesions has excellent outcomes. It may also offer a balance between the efficacy of complete oncologic resection and postoperative quality of life in the treatment of rectal cancer. In some cases, it may be considered an alternative to radical surgery.

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.

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.

The outcome of local excision of large rectal polyps by transanal endoscopic microsurgery.

Introduction: Local excision of large rectal polyps can be an alternative for radical rectal resection with total mesorectal excision. We aim to report the functional and oncological outcomes of transanal endoscopic microsurgery (TEM) for patients with large rectal polyps. Methods: All demographic and clinical data of patients who underwent TEM for rectal polyp of 5 cm or more at the Hasharon Hospital from 2005 to 2018 were retrospectively reviewed. Results: Twenty-eight patients were included. The mean age was 66 years. The mean polyp size was 6.2 cm (range: 5-8.5 cm) with a mean distance of 8.3 cm from the anal verge. Peritoneal entry during TEM was observed in five patients and additional laparoscopy after the completion of the TEM was performed in four patients. There were no major perioperative complications. Seven patients had minor complications. Final pathology revealed T1 carcinoma in five patients and T2 carcinoma in three patients. Re-TEM was performed in one patient with involved margins with adenoma. After a median follow-up of 64 months, one patient had local recurrence. Conclusion: TEM is an acceptable technique for the treatment of large polyps with minor complications and a reasonable recurrence rate. TEM may be considered regardless of the size of the rectal polyp.

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.

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.

Activity Tracking After Surgery: Does It Correlate With Postoperative Complications?

BACKGROUND: Postoperative ambulation is an important tenet in enhanced recovery programs. We quantitatively assessed the correlation of decreased postoperative ambulation with postoperative complications and delays in gastrointestinal function. METHODS: Patients undergoing major abdominal surgery were fitted with digital ankle pedometers yielding continuous measurements of their ambulation. Primary endpoints were the overall and system-specific complication rates, with secondary endpoints being the time to first passage of flatus and stool, the length of hospital stay, and the rate of readmission. RESULTS: 100 patients were enrolled. We found a significant, independent inverse correlation between the number of steps on the first and second postoperative days (POD1/2) and the incidence of complications as well as the recovery of GI function and the likelihood of readmission (P < .05). POD2 step count was an independent risk factor for severe complications (P = .026). DISCUSSION: Digitally quantified ambulation data may be a prognostic biomarker for the likelihood of severe postoperative complications.

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.

Liver Cancer Has a Distinctive Profile in Black Patients: Current Screening Guidelines May Be Inadequate.

There is mounting evidence that Black patients develop more advanced liver cancers with less advanced liver disease. These findings have important implications for the future of liver cancer screening.

Lymphocyte-to-monocyte ratio predicts survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Aim: Lymphocyte-to-monocyte ratio (LMR) predicts overall survival (OS) in patients with colorectal cancer. We explored LMR in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Materials & methods: We identified all patients undergoing CRS/HIPEC for colorectal or appendiceal adenocarcinoma at our institution. We analyzed LMR's relationship with clinicopathologic variables with Kaplan-Meier log-rank survival analyses and multivariable Cox regression models with 5-year OS. Results: Two hundred and sixteen patients underwent CRS/HIPEC. Five-year OS for low LMR (≤3.71) was 35.2 versus 60.4% for elevated LMR (hazard ratio [HR]: 2.0; 95% CI: 1.1-3.5; p = 0.02). On multivariable Cox-regression, elevated LMR was significantly associated with OS (p ≤ 0.05). Conclusion: LMR is an independent predictor of OS in patients undergoing CRS/HIPEC for colorectal and appendiceal adenocarcinoma.

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.

Commensal fungi and their cell-wall ß-glucans direct differential responses in human intestinal epithelial cells.

Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that ß-glucans, major fungal cell-wall glycans, induced chemokine secretion by IEC lines in a Dectin-1- and Syk-dependent manner. Here, we show that in contrast to ß-glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL-8, CCL2, CXCL1, and GM-CSF. Commensal fungi and ß-glucans activated Syk and ERK in IEC lines. However, only ß-glucans activated p38, JNK, and the transcription factors NF-κB p65 and c-JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with ß-glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with ß-glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines. Lack of cytokine secretion in response to commensal fungi may reflect IECs' response to fungal glycans, other than ß-glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation.