Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150.

The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.

Liver metastasis 13 years after the resection of a malignant triton tumor originating in the duodenum.

This is an additional case report of a malignant triton tumor arising in the duodenum that was removed by pancreatoduodenectomy. Liver and gallbladder dysfunctions were detected in a regular blood examination during a follow-up for hypertension in a 62-year-old woman with a previous surgical history for a malignant Triton tumor in the duodenum 13 years ago. Further examinations revealed a metastatic liver tumor originating from the malignant triton tumor in the duodenum. Since the progression of the liver tumor was detected after radiation therapy, complete resection was performed by right hepatectomy. Curative hepatectomy resulted in disease-free survival for 1 year and 5 months in an extremely rare case of liver metastasis derived from a malignant triton tumor in the duodenum.

Genomic profiling of intestinal/mixed-type superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIM: The mechanism underlying carcinogenesis and the genomic features of superficial non-ampullary duodenal epithelial tumors (SNADETs) have not been elucidated in detail. In this study, we examined the genomic features of incipient SNADETs, such as small lesions resected via endoscopic treatment, using next-generation sequencing (NGS). METHODS: Twenty consecutive patients who underwent endoscopic treatment for SNADETs of less than 20 mm between January and December 2017 were enrolled. Targeted genomic sequencing was performed through NGS using a panel of 160 cancer-related genes. Furthermore, the alteration/mutation frequencies in SNADETs were examined. RESULTS: The maximum size of the SNADETs examined in this study was 12 mm in diameter. Five SNADETs were classified as low-grade dysplasia (LGD) tumors, while 14 SNADETs were classified as high-grade dysplasia tumors. Only one carcinoma in situ was detected. NGS data for 16 samples were obtained. APC alterations were detected in 81% of samples (13/16). KRAS, BRAF, and TP53 alterations were detected in 25% (4/16), 18.8% (3/16), and 6.3% (1/16) of cases, respectively. CONCLUSION: We detected APC alterations in most small SNADETs resected via endoscopic treatment, from LGD to carcinoma samples. Even in SNADETs classified as small LGD exhibited KRAS and BRAF alterations.

Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria.

AIM: This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial). METHODS: In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression-free-survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial. RESULTS: Of the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child-Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child-Pugh-score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS. CONCLUSION: Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.

Malignant triton tumor of the duodenum: report of a case.

We report a case of malignant triton tumor of the duodenum, which is extremely rare. A submucosal malignant tumor was detected in the duodenum of a 49-year-old woman. The tumor was completely resected by performing pancreaticoduodenectomy. Pathological examination revealed that the lesion was a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, i.e., a malignant triton tumor. Long-term survival has been achieved with no recurrence at 8.5 years after surgery.

Single-stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis: a multicenter, non-randomized, open-label and exploratory clinical trial.

BACKGROUND: Two-stage treatment involving stone removal after drainage is recommended for mild to moderate acute cholangitis associated with choledocholithiasis. However, single-stage treatment has some advantages. We aimed to assess the efficacy and safety of single-stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis. METHODS: A multicenter, non-randomized, open-label, exploratory clinical trial was performed in 12 institutions. A total of 50 patients with a naïve papilla and a body temperature ≥37 °C who were diagnosed with mild to moderate cholangitis associated with choledocholithiasis were enrolled between August 2012 and February 2014. RESULTS: Of the 50 patients, 15 had mild cholangitis and 35 had moderate cholangitis. The median number of common bile duct stones was 2 (range, 1-8), and the median diameter of the common bile duct stones was 7.5 mm (range, 1-18). The cure rate of acute cholangitis within 4 days after single-stage treatment was 90% (45/50) based on a body temperature <37 °C for ≥24 h. The incidence of complications was 10% (5/50). CONCLUSION: Single-stage endoscopic treatment may be effective and safe for mild to moderate acute cholangitis associated with choledocholithiasis (clinical trial registration number: UMIN000008494).

[A case of sigmoid colon cancer with lymphangitis carcinomatosa successfully treated with chemotherapies including molecular targeting drugs].

A 51-year-old man was referred to our hospital with adenocarcinoma of sigmoid colon with multiple lymph node metastasis. At the time of admission, he had dyspnea, and computed tomography (CT) showed typical signs of lymphangitis carcinomatosa of the lung. Combination of mFOLFOX6 and bevacizumab was started. After start of the therapy, CT revealed an improvement in lymphangitis carcinomatosa. 8 months later, the tumor assessment became progressive disease. FOLFIRI was started as the second-line chemotherapy, but the patient did not respond. Then, dyspnea emerged again, and CT indicated the lymphangitis carcinomatosa had become worse. So as the third-line chemotherapy, combination of irinotecan and cetuximab was started. Dyspnea immediately disappeared, and CT showed an improvement of lymphangitis carcinomatosa. In the previous literature, malignant tumor cases which accompany lymphangitis carcinomatosa might always have a poor course. Our case dramatically responded to the chemotherapy including molecular targeting drug and showed a long survival. So we conclude that aggressive chemotherapy including a molecular targeting drug may be recommended in a case of colorectal cancer which accompanies lymphangitis carcinomatosa of the lung.

Hepatitis E Virus (HEV) strains in serum samples can replicate efficiently in cultured cells despite the coexistence of HEV antibodies: characterization of HEV virions in blood circulation.

We recently developed a cell culture system for hepatitis E virus (HEV) in PLC/PRF/5 and A549 cells, using fecal specimens from HEV-infected patients. Since transfusion-associated hepatitis E has been reported, we examined PLC/PRF/5 and A549 cells for the ability to support replication of HEV in various serum samples obtained from 23 patients with genotype 1, 3, or 4 HEV. HEV progenies emerged in culture media of PLC/PRF/5 cells, regardless of the coexistence of HEV antibodies in serum but dependent on the load of HEV inoculated (31% at 2.0 x 10(4) copies per well and 100% at >or=3.5 x 10(4) copies per well), and were successfully passaged in A549 cells. HEV particles in serum, with or without HEV antibodies, banded at a sucrose density of 1.15 to 1.16 g/ml, which was markedly lower than that for HEV particles in feces, at 1.27 to 1.28 g/ml, and were nonneutralizable by immune sera in this cell culture system. An immuno-capture PCR assay of HEV virions treated with or without detergent indicated that HEV particles in serum are associated with lipids and HEV ORF3 protein, similar to those in culture supernatant. By immunoprecipitation, it was found that >90% of HEV particles in the circulation exist as free virions not complexed with immunoglobulins, despite the coexistence of HEV antibodies. These results suggest that our in vitro cell culture system can be used for propagation of a wide variety of HEV strains in sera from various infected patients, allowing extended studies on viral replication specific to different HEV strains.