Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States.

Background :   Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI). Methods: Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves. Results: MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011). Conclusion: In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

Packed with pills - obstructing duodenal web in the setting of intestinal malrotation: A case report.

BACKGROUND: The incidence of intestinal malrotation in adults has been reported to only be about 0.2%. Duodenal web as a cause of intestinal obstruction is rare, with an incidence of about 1:20000-1:40000. Furthermore, when described, these conditions are usually seen in early life and very infrequently in adulthood. CASE SUMMARY: We report a case of a middle-aged woman with intestinal malrotation who presented with a three-month history of right-sided abdominal pain, early satiety, and a 22-pound weight loss. Patient underwent an esophagogastroduodenoscopy, which demonstrated numerous retained pills in a deformed first portion of the duodenum, concerning for a partial gastric outlet obstruction. An upper gastrointestinal series showed marked distention of the proximal duodenum with retained debris and the presence of a windsock sign, increasing the suspicion of a duodenal web. The patient subsequently underwent surgical intervention where a duodenal web with two lumens was noted and resected, opening the duodenum. There were over 150 pill capsules that were removed. The patient is doing well after this intervention. CONCLUSION: Both intestinal malrotation and duodenal webs are infrequently encountered in the adult population. These pathologies can also present with nonspecific abdominal symptoms such as chronic abdominal pain and nausea. Hence, providers might not consider these pathologies in the differential for patients who present with vague symptoms which can lead to delay in management and increased mortality and morbidity.

Induction Chemotherapy With FOLFIRINOX Followed by Chemoradiation With Gemcitabine in Patients With Borderline-Resectable Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Perioperative therapy is standard for patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC); however, an optimal neoadjuvant regimen is lacking. We assessed the efficacy of FOLFIRINOX chemotherapy followed by gemcitabine-based chemoradiation as preoperative therapy. METHODS: Patients received 4 cycles of FOLFIRINOX, followed by 6-weekly gemcitabine with concomitant intensity-modulated radiation. The primary endpoint was the R0 resection rate. Secondary outcomes included resection rate, overall-response, overall survival (OS), progression-free survival (PFS), and tolerability. The trial was terminated early due to slow accrual. A Simon's optimal two-stage phase II trial single arm design was used. The primary hypothesis of treatment efficacy was tested using a multistage group sequential inference procedure. The secondary failure time analysis endpoints were assessed using the Kaplan-Meier procedure and the Cox regression model. RESULTS: A total of 22 patients enrolled in the study, 18 (81.8%) completed neoadjuvant treatment. The bias corrected R0 rate was 55.6% (90% CI: 33.3, 68.3; P value = .16) among patients that received at least 1 cycle of FOLFIRINOX and was 80% among patients that underwent surgery. The median OS was 35.1 months. The median PFS among patients that underwent surgery was 34 months. CONCLUSION: An R0 resection rate of 55.6% is favorable. Neoadjuvant FOLFIRINOX followed by concomitant Gemcitabine with radiation was well-tolerated. NCT01897454.

Association of Addition of Ablative Therapy Following Transarterial Chemoembolization With Survival Rates in Patients With Hepatocellular Carcinoma.

Importance: Hepatocellular carcinoma (HCC) is a heterogeneous disease with many available treatment modalities. Transarterial chemoembolization (TACE) is a valuable treatment modality for HCC lesions. This article seeks to evaluate the utility of additional ablative therapy in the management of patients with HCC who received an initial TACE procedure. Objective: To compare the overall survival (OS) and freedom from local progression (FFLP) outcomes after TACE alone with TACE that is followed by an ablative treatment regimen using stereotactic body radiation therapy, radiofrequency ablation, or microwave ablation for patients with HCC. Design, Setting, and Participants: This cohort study of 289 adults at a single urban medical center examined survival outcomes for patients with nonmetastatic, unresectable HCC who received ablative therapies following TACE or TACE alone from January 2010 through December 2018. The Lee, Wei, Amato common baseline hazard model was applied for within-patient correlation with robust variance and Cox regression analysis was used to assess the association between treatment group (TACE vs TACE and ablative therapy) and failure time events (FFLP per individual lesion and OS per patient), respectively. In both analyses, the treatment indication was modeled as a time-varying covariate. Landmark analysis was used as a further sensitivity test for bias by treatment indication. Exposures: TACE alone vs TACE followed by ablative therapy. Main Outcomes and Measures: Freedom from local progression and overall survival. Hypotheses were generated before data collection. Results: Of the 289 patients identified, 176 (60.9%) received TACE only and 113 (39.1%) received TACE plus ablative therapy. Ablative therapy included 45 patients receiving stereotactic body radiation therapy, 39 receiving microwave ablation, 20 receiving radiofrequency ablation, and 9 receiving a combination of these following TACE. With a median (interquartile range) follow-up of 17.4 (9.5-29.5) months, 242 of 512 (47.3%) lesions progressed, 211 in the group with TACE alone and 31 in the group with TACE plus ablative therapy (P < .001). Over 3 years, FFLP was 28.1% for TACE alone vs 67.4% for TACE with ablative therapy (P < .001). The 1-year and 3-year OS was 87.5% and 47.1% for patients with lesions treated with TACE alone vs 98.7% and 85.3% for patients where any lesion received TACE plus ablative therapy, respectively (P = .01), and this benefit remained robust on landmark analyses at 6 and 12 months. The addition of ablative therapy was independently associated with OS on multivariable analysis for all patients (hazard ratio, 0.26; 95% CI, 0.13-0.49; P < .001) and for patients with Barcelona clinic liver cancer stage B or C disease (hazard ratio, 0.31; 95% CI, 0.14-0.69; P = .004). Conclusions and Relevance: Adding ablative therapy following TACE improved FFLP and OS among patients with hepatocellular carcinoma. This study aims to guide the treatment paradigm for HCC patients until results from randomized clinical trials become available.

Draining T-Tube Jejunostomy: A Technique to Get Out of Trouble.

A perforated viscus in the postpancreaticoduodenectomy setting is a rare phenomenon and a devastating complication. In this situation, adherence to damage-control principles demands minimizing the operative intervention while addressing the intestinal perforation as a way to mitigate the injurious effects on a complex gastrointestinal reconstruction. Herein, we describe our intraoperative decision-making with an unconventional approach in the management of a perforated viscus in the postpancreaticoduodenectomy setting using a draining T-tube jejunostomy. Our patient recovered remarkably well from this and was discharged from the hospital in six days with a controlled draining T-tube jejunostomy, which was subsequently removed on postoperative day 35. Our case illustrates an important option when dealing with a perforated viscus in the complex gastrointestinal surgery patient that has minimal morbidity, adequate source control, and the potential for an excellent clinical outcome. As surgical care continues to be delivered in a specialty-driven manner, a draining T-tube jejunostomy presents the ideal technique to get out of trouble for the general surgeon practicing in the community who may not be as experienced with complex gastrointestinal surgery.

Reconstruction of the replaced right hepatic artery at the time of pancreaticoduodenectomy.

BACKGROUND: The arterial anatomy supplying the liver is highly variable. One of the most common variants is a completely replaced right hepatic artery which is seen in about 11% of the population. Interruption of arterial flow to the right hepatic artery at the time of pancreaticoduodenectomy has been associated with biliary fistula and the consequent complications, as well as stenosis of the biliary enteric anastomosis. Malignancies of the posterior aspect of the head of the pancreas can encase a replaced right hepatic artery without involvement of other vascular structures. In this situation, it is possible to resect and reconstruct the replaced right hepatic artery to maintain oxygen delivery to the biliary enteric anastomosis. SUMMARY: Herein we describe a technique to reconstruct a replaced right hepatic artery following resection of the vessel en bloc with the tumor during a pancreaticoduodenectomy, using inflow from the gastroduodenal artery.

Extended-donor criteria liver allografts.

Extended-donor criteria liver allografts do not meet traditional criteria for transplantation. Although these organs offer immediate expansion of the donor pool, transplantation of extended-donor criteria liver allografts increases potential short- and long-term risk to the recipient. This risk may manifest as impaired allograft function or donor-transmitted disease. Guidelines defining this category of donor, level of acceptable risk, principles of consent, and post-transplantation surveillance have not been defined. This article reviews the utilization, ethical considerations, and outcomes of extended-donor criteria liver allografts.

One-year morbidity after donor right hepatectomy.

Live donors are becoming an increasingly important source of donor organs in liver transplantation; however, long-term functional aspects of recovery from donor right hepatectomy are unknown. We analyzed donor outcomes at 1-year follow-up. We performed a single-center retrospective analysis of 70 right hepatectomy donors. Six-week and 1-year postoperative follow-up results were compared to preoperative baseline values. Ultrasonography was performed in all donors at 6 weeks and as clinically indicated. All donors were alive and well at the end of the study period. Of 66 right hepatic donors, only 22 (32%) were fully compliant with a 1-year follow-up visit. All those not compliant were contacted by phone. All complications except 1 (late finding of portal vein thrombosis) occurred in the perioperative (90-day) period. The incidence of bile leak was 4.3%, incisional hernia 20%, and autologous transfusion 1.0%. There were no aborted procedures. In those compliant with full 1-year follow-up, total bilirubin, aspartate aminotransferase, and alanine aminotransferase were normal in 97%. A total of 5 donors were noted to have persistence of asymptomatic thrombocytopenia beyond the perioperative period (90 days). These were investigated with Doppler sonography. Sonography was unremarkable in 3 of the 5, while 2 had abnormal findings: splenomegaly alone in 1, and splenomegaly with portal vein thrombosis in the other. Magnetic resonance angiography was performed in both, and the patient with portal vein thrombosis underwent endoscopy, which failed to reveal varices. Neither has clinical portal hypertension. Both remain asymptomatic albeit with stable thrombocytopenia. In conclusion, the majority of complications after donor right hepatectomy occur in the perioperative period. Later findings may include asymptomatic thrombocytopenia, with an incidence possibly as high as 23%, though the significance of this finding remains uncertain. Larger-scale studies are needed to confirm the true incidence and clinical significance of persistent thrombocytopenia in the donor hepatectomy population. Strategies to improve compliance with 1-year follow-up visits need to be developed.

Enhanced development of caspase-independent cortical cell death during cold storage in kidneys of non-heart-beating donors.

BACKGROUND: Understanding the mechanisms of injury associated with cardiac arrest is essential for defining strategies aimed at improving preservation and function of kidneys harvested in non-heart-beating (NHB) donors. METHODS: We standardized a model of NHB donors in rats and studied the kinetics and types (apoptosis vs. necrosis) of renal cell death developing during cold storage. Using quantitative polymerase chain reaction, immunoblotting, and caspase inhibition, we also studied the molecular pathways regulating renal cell death in this model. RESULTS: The kinetics and extent of cell death developing in cortical tubules during cold storage were found to be increased in non-heart-beating (NHB) kidneys. Apoptosis of cortical tubules predominated in NHB kidneys exposed to 10 hr of cold storage, whereas necrosis increased after longer periods of cold ischemia. Shortly after cardiac arrest, a rapid up-regulation of Bax and Hsp 70 was found at the protein level in NHB kidneys. After 24 hr of cold storage, induction of Bax was maintained, whereas protein levels of Hsp70 returned to levels comparable to heart-beating (HB) controls. Also, mRNA levels of Bax were found to increase during cold storage in NHB kidneys. Cortical cell death was found to be largely caspase-independent but responsive to hydroxyl-radical scavenging with dimethyl sulfoxide (DMSO). CONCLUSIONS: Cardiac arrest promotes activation of death-inducing molecules such as Bax and is associated with increased development of caspase-independent renal cell death during cold storage. Developing strategies, such as free radical scavenging, aimed at inhibiting cell death during cold storage, could prove useful for improving preservation of NHB kidneys.