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Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or super selective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, super selective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and three patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Discussion/Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.

Abstract  We report a case of serous cystadenoma of pancreas causing left-sided portal hypertension and gastric varices. A 68-year-old man was admitted for treatment of a pancreatic body tumor. Contrast-enhanced computed tomography (CT) showed a honeycombed cystic mass. A celiac angiogram showed a hypervascular tumor supplied mainly by a dilated splenic artery and dorsal pancreatic artery. In the venous phase, the patent splenic vein had a large hepatopetal collateral vein via the coronary gastric vein. Upper gastrointestinal endoscopy showed isolated varices of the gastric fundus. We made a preoperative diagnosis of a serous cystic tumor of the pancreas with left-sided portal hypertension and performed distal pancreatectomy with splenectomy. The resected tumor was 8 cm in diameter and had a typical honeycombed microcystic pattern with central stellate scarring. The spleen was not enlarged. Histopathological examination confirmed a diagnosis of serous cystadenoma without any sign of malignancy. Postoperative endoscopy showed disappearance of the gastric varices. [ABSTRACT FROM AUTHOR]

Pd nanoparticles exhibit the abnormal behavior of the Pd lattice expanding as the size of the Pd nanoparticles decreases. We measured extended X-ray absorption fine structure of poly(N-vinyl-2-pyrrolidone)-protected Pd nanoparticles and confirmed that the PdPd bond distance in small Pd nanoparticles with a diameter of less than 3 nm was elongated by 2% compared with that in Pd foil. The origin of the unusual bond elongation was discussed. [ABSTRACT FROM AUTHOR]

Abstract  Hormone replacement therapy (HRT) containing estrogens is generally used to relieve climacteric symptoms and to prevent osteoporosis and coronary heart disease [1], however, there has been increasing evidence of the HRT as the risk of hormone-dependent neoplasms including breast cancer [2], uterine endometrial cancer [3], ovarian cancer [4], and even lung cancer [5]. Noteworthy is mucinous cyst neoplasms (MCNs) of the pancreas, characterized by mucin-producing columnar epithelium supported by “ovarian-like” mesenchymal stroma, occur mostly in females expressing estrogen receptors [6, 7]. Although several reports regarding the closed relationship between MCNs and pregnancy [8, 9] might imply potential sex hormone-dependency of the MCNs [10], no correlation has been reported. This is the first case report of malignant MCN developing during continuous HRT after hysterectomy. [ABSTRACT FROM AUTHOR]

Bowel endometriosis is a condition caused by endometrial glands and stroma infiltrating the bowel wall and reaching the subserous fat tissue or the adjacent subserous plexus. A 42-year-old woman with changes in stool habits, nausea, and stomach aches experienced complete obstruction in the rectum. Endoscopic ultrasound demonstrated a low echoic lesion outside the rectal mucosa and endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of bowel endometriosis. The clinical characteristics of bowel endometriosis are unspecific and this condition is sometimes misdiagnosed as a malignant tumor, irritable bowel syndrome, or any other colorectal disorder. Our aim is to show that endoscopic ultrasound-guided fine needle aspiration might be helpful for bowel endometriosis diagnosis and exclusion of other malignant disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is unclear whether Child-Pugh score discriminates a prognosis of the Child-Pugh A patients who underwent hepatic resection for hepatocellular carcinoma. METHODS: Between April 2000 and March 2011, 361 patients with Child-Pugh A who underwent curative hepatectomy were divided into 2 groups: Child-Pugh score 5 points group (CPS5) and Child-Pugh score 6 points group (CPS6); both CPS5 (n = 274) and CPS6 (n = 87) groups were compared. RESULTS: Overall survival rates (1/2/5 years of the CPS5 and CPS6 groups groups were 90.9%/82.5%/62.4% and 80.6%>/68.0%>/47.6%>, respectively) and disease-free survival rates (67.6%>/51.8%>/30.1%> and 36.9%/16.0%/5.9%, respectively) showed that the CPS5 group was significantly better than the CPS6 group. Multivariate analysis revealed that Child-Pugh score at overall survival (P = .0125) and disease-free survival (P = .0103) was a significant prognostic factor. CONCLUSIONS: The overall survival and disease-free survival in Child-Pugh A showed quite a difference between the CPS5 and CPS6 groups. However, CPS5 and CPS6 may be a useful prognostic marker of hepatocellular carcinoma patients with hepatic resection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Age-related differences of clinicopathologic features, outcomes, and molecular properties of hepatocellular carcinoma remain unclarified. METHODS: We classified patients who underwent hepatectomy for hepatocellular carcinoma into 3 groups by age bracket; younger group (<50 years), middle-aged group (50 to 79 years), and elderly group (≥80 years) and compared age-related features. RESULTS: Hepatitis viral infection was dominant in the younger group (hepatitis B virus [HBV]; 67%) and middle-aged group (hepatitis C virus [HCV]; 56%), whereas the elderly group showed a significantly higher rate without hepatitis virus infection (absence of HBV and HCV infection, 66%; P = .0001). There was a significantly greater proportion of age-associated preexisting comorbidity in the elderly group (89%; P = .0004). Liver cirrhosis in the elderly group (24%) was significantly lower than other groups (younger, 67%; middle-aged, 50%; P = .0058). There was no significant difference in perioperative and postoperative outcomes among these groups. Microarray analysis revealed age-related upregulation of androgen and phosphatidylinositol 3-kinase pathways in the tumor tissue and downregulation of the fibrosis-related pathways in the noncancerous liver tissue. CONCLUSIONS: Based on increased correlation with the absence of HBV and HCV infection and pre-existing comorbidity, the age-related carcinogenic pathways might play a critical role in elderly hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: In patients with solitary hepatocellular carcinoma ±5 cm without macrovascular invasion, it is unknown whether the initial anatomic resection improves the long-term survival. METHODS: Among 545 initial hepatectomies for hepatocellular carcinoma between 2000 and 2012, the 233 patients with the aforementioned criteria of hepatocellular carcinoma were enrolled. RESULTS: The mean observation time was 1,125 days. Disease-free 5-year survival rates with and without anatomic resection were 46% and 23%, respectively (P 5=.009). Multivariate analyses for disease-free survival rates revealed the risk factors to be a-fetoprotein (odds ratio, 1.6; P 5 .028) and anatomic resection (odds ratio, .7; P 5.048), while increased Child-Pugh score (>5) was the only independent risk factor for overall survival (odds ratio, 1.8; P 5.043). The 5-year overall survival rates with and without Child-Pugh score 5 were 74% and 40%, respectively (P < .0001, log-rank test). CONCLUSIONS: Initial anatomic resection for small solitary hepatocellular carcinoma without macrovascular invasion improved disease-free survival rates remarkably [ABSTRACT FROM AUTHOR]