Conversion surgery after successful response to chemotherapy (S-1 + oxaliplatin + nivolumab) in a patient with stage IV gastric cancer with peritoneal metastasis (P1, CY1): a case report.

We here present a case report of a patient with Stage IV gastric cancer with peritoneal metastasis (P1, CY1) who underwent conversion surgery after a successful response to chemotherapy (S-1 + oxaliplatin + nivolumab). The patient was a woman in her 60 s. Her chief complaint was epigastric pain. Upper gastrointestinal endoscopy showed Type 4 advanced carcinoma on the lesser curvature of the gastric body. Biopsy showed Group 5 (poorly differentiated adenocarcinoma) and HER2 was negative. Staging laparoscopy revealed seeding in the round ligament of the liver (P1) and adenocarcinoma cells in ascites (CY1). Ten courses of chemotherapy (S-1 + oxaliplatin + nivolumab) were administered, after which contrast-enhanced computed tomography showed that the primary tumor had shrunk and seeding was no longer detectable. Upper gastrointestinal endoscopy revealed scar-like changes. A second staging laparoscopy revealed that ascites cytology was negative and a biopsy of the round ligament of the liver showed no malignant cells (P0, CY0). Conversion surgery comprising laparoscopic total gastrectomy with D2 lymph node dissection and resection of the round ligament of the liver was performed. The postoperative course was uneventful. Histopathological examination of the resected specimen revealed no tumor cells in the gastric mesentery or the round ligament of the liver. The pathological diagnosis was gastric cancer [M, U, L, Less, Ant, Post, type4, T3(SS), N0, M0 (H0, P0, CY0), ypStage IIA]. Adjuvant chemotherapy (S-1) was commenced. The patient is still alive 7 months later with no evidence of recurrence.

Effects of green light-emitting diode irradiation on hepatic differentiation of hepatocyte-like cells generated from human adipose-derived mesenchymal cells.

Light-emitting diode (LED) irradiation has been used in the differentiation of mesenchymal stem cells into a variety of cell types. This study investigated the effect of green LED (GLED) irradiation on the differentiation of adipocyte-derived mesenchymal cells into hepatocyte-like cells (HLCs) and the mechanism of its action. HLCs in the hepatocyte maturation phase were irradiated with GLED (520 nm, 21 W/m2, 5 min/day for 10 days). The cells were then assessed for expression of hepatocyte maturity genes and opsin 3 (OPN3), hepatocyte function, viability, apoptosis, and levels of reactive oxygen species (ROS), intracellular adenosine triphosphate (ATP) and calcium ions (Ca2+). GLED irradiation increased Alpha-1 antitrypsin and Ornithine transcarbamylase gene expression, promoted Cytochrome P450 3A4 activity and urea synthesis, and elevated intracellular ROS, ATP and Ca2+ levels. OPN3 expression was significantly more upregulated in GLED-irradiated HLCs than in the non-irradiated HLCs. No significant difference in cell viability or apoptosis was observed between GLED-irradiated and non-irradiated HLCs. GLED irradiation can promote hepatocyte maturation and functions through OPN3. GLED irradiation also stimulated mitochondrial function via Ca2+/ATP/ROS activation. GLED irradiation has potential to support cell-based transplantation in patients.

Association between high expression of intratumoral fibroblast activation protein and survival in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to exhibit protumorigenic effects. Among the well-known CAF markers such as smooth muscle actin (SMA) and fibroblast activation protein (FAP), high expression of SMA in the peritumoral stroma has been reported to be a prognostic factor in various cancers. However, the effect of high FAP expression in intrahepatic cholangiocarcinoma (IHCC) has not been fully clarified. We evaluated the expression of CAF markers, focusing on FAP expression in the peripheral and intratumoral regions, to clarify the association with survival in patients with IHCC. METHODS: The study cohort comprised 37 patients who underwent curative resection for IHCC. The FAP expressions were evaluated in the peripheral and intratumoral regions of the resected tissues. Clinicopathological factors and survival outcomes were investigated between patients with high versus low FAP expression. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival and relapse-free survival. RESULTS: The median area percentages of FAP expression in the peripheral and intratumoral regions were 15.5% and 17.8%, respectively. High FAP expression in the intratumoral region was significantly associated with worse overall survival and disease-free survival than low FAP expression in the intratumoral region. Multivariate analysis identified high intratumoral FAP expression as a risk factor for worse overall survival (hazard ratio, 2.450; p = 0.049) and relapse-free survival (hazard ratio, 2.743; p = 0.034). CONCLUSIONS: High intratumoral FAP expression was associated with worse survival, suggesting that intratumoral FAP expression represents malignant progression in patients with IHCC.

Impact of pancreatic resection in patients with liver cirrhosis.

BACKGROUND: Several reports have shown a high mortality rate in patients with liver cirrhosis (LC) who undergo pancreaticoduodenectomy, however, there are few reports on its long-term prognosis. METHODS: Twelve patients with LC who had undergone pancreatic resection were enrolled. To compare clinicopathological variables, 159 non-LC patients who had undergone resection for pancreatic cancer were enrolled. RESULTS: Pancreaticoduodenectomy (PD) was performed in 5 LC patients and distal pancreatectomy (DP) was performed in 7 LC patients. Patients in the LC group had more co-morbidities, lower platelet counts and higher Fib4 index than the non-LC group. The postoperative complication rate was higher in the LC group (83.3% vs 47.8%). While the postoperative hospital stay and 30-day mortality rate were not different, the 90-day mortality rate was higher in the LC group (25.0% vs 2.5% ; p<0.01). Comparison by operative procedure showed no significant differences of postoperative outcomes in DP cases. However, in PD cases, postoperative complications were more frequent (100% vs 42.3%) and 90-day mortality was higher (40.0% vs 2.9% ; p<0.01) in the LC group. CONCLUSIONS: PD resulted in higher postoperative morbidity and mortality rates in patients with LC compared with non-LC patients. DP could be tolerated in the LC patients. J. Med. Invest. 70 : 189-194, February, 2023.

Transanal lateral lymph node dissection with intraoperative hologram support in low rectal cancer.

BACKGROUND: In Japan, the standard treatment for stage II/III advanced low rectal cancer is total mesorectal excision plus lateral lymph node dissection (LLND). There are also recent reports on the use of transanal LLND. However, the transanal anatomy is difficult to understand, and additional support tools are required to improve the surgical safety. The present study examined the utility of holograms with mixed reality as an intraoperative support tool for assessing the complex pelvic anatomy. METHODS: Polygon (stereolithography) files of patients' pelvic organs were created and exported from the SYNAPSE VINCENT imaging system and uploaded into the Holoeyes MD virtual reality software. Three-dimensional images were automatically converted into patient-specific holograms. Each hologram was then installed into a head mount display (HoloLens2), and the surgeons and assistants wore the HoloLens2 when they performed transanal LLND. Twelve digestive surgeons with prior practice in hologram manipulation evaluated the utility of the intraoperative hologram support by means of a questionnaire. RESULTS: Intraoperative hologram support improved the surgical understanding of the lateral lymph node region anatomy. In the questionnaire, 75% of the surgeons answered that the hologram accurately reflected the anatomy, and 92% of the surgeons answered that the anatomy was better understood by simulating the hologram intraoperatively than preoperatively. Moreover, 92% of the surgeons agreed that intraoperative holograms were a useful support tool for improving the surgical safety. CONCLUSIONS: Intraoperative hologram support improved the surgical understanding of the pelvic anatomy for transanal LLND. Intraoperative holograms may represent a next-generation surgical tool for transanal LLND.

Myosin light chain of shark fast skeletal muscle exhibits intrinsic urea-resistibility.

Marine elasmobranch fish contain urea, a protein denaturant, in their bodies. The urea-trimethylamine N-oxide (TMAO) counteraction mechanism contributes to urea-resistibility, where TMAO compensates for protein denaturation by urea. However, previous studies revealed that shark fast skeletal muscle myosin exhibits native activity at physiological urea concentrations in the absence of TMAO, suggesting that shark myosin has urea-resistibility. In this study, we compared the urea-resistibility of myosin alkali light chains (A1-LC and A2-LC) from banded houndshark and carp by examining the α-helical content at various urea concentrations. The α-helical content of carp myosin A1-LC and A2-LC gradually decreased as urea concentrations increased to 2 M. In contrast, the α-helical content of banded houndshark A1-LC increased between 0 and 0.5 M urea, and the α-helical content of A2-LC remained constant until 0.5 M urea. We determined the full-length sequences of the banded houndshark myosin light chains (A1-LC, A2-LC and DTNB-LC). Hydrophilicity analysis revealed that the N-terminal region (residues 28-34) of A1-LC from banded houndshark is more hydrophilic than the corresponding region of A1-LC from carp. These findings support the notion that shark myosin exhibits urea-resistibility independent of the urea-TMAO counteraction mechanism.

Carcinogenic risk in the biliary epithelium of children with congenital biliary dilatation via the DNA damage repair pathway.

PURPOSES: Congenital biliary dilatation (CBD) is a high-risk factor for biliary tract cancer (BTC). We previously reported the potential for carcinogenesis in the biliary epithelium of patients with CBD. In this study, we investigated potential carcinogenetic pathways, focusing on the DNA damage repair response, in children with CBD and compared the findings with those in adults. METHODS: We enrolled 6 children with CBD and 10 adults with CBD without BTC who underwent extrahepatic bile duct resections, plus 4 control patients who underwent pancreaticoduodenectomy for non-biliary cancer. Levels of phosphorylated histone H2AX (γH2AX), MRE11, and Ku-70 in the biliary tract epithelium were evaluated by immunohistochemistry. RESULTS: The levels of γH2AX, MRE11, and Ku-70 were significantly higher in the gallbladder epithelium and bile duct epithelium of both children and adults than in controls. CONCLUSIONS: Children and adults with CBD might develop BTC via the DNA damage repair pathway, as evidenced by increased γH2AX, MRE11, and Ku-70 expression.

Multiplication of tumor maximum diameter and number as a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage hepatocellular carcinoma.

AIM: Recent advances in treatment modalities have been made, limiting the indication of hepatic resection in the treatment strategy for hepatocellular carcinoma (HCC) patients. This retrospective study investigated the significance of multiplication of tumor maximum diameter and number (MDN) as a surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC. METHODS: A total of 49 patients with Barcelona Clinic Liver Cancer intermediate-stage HCC who underwent curative hepatic resection between 2000 and 2020 were enrolled in this study. Prognostic factors of overall survival and disease-free survival, including the product of MDN, were analyzed. RESULTS: Patients with MDN >12 experienced significantly worse prognosis compared with those with MDN ≤12 (p = 0.0395), and 5-year overall survival rates after hepatic resection were 60.0% and 23.4%, respectively. Furthermore, the disease-free survival rate of patients with MDN >12 was significantly worse compared with those with MDN ≤12 (p = 0.0049), and all patients with MDN >12 experienced recurrence within 3 years after hepatic resection. In the multivariate analysis, MDN >12 was identified as the only independent prognostic factor of both overall survival and disease-free survival. In addition, patients with MDN >12 suffered from uncontrollable recurrence by locoregional treatment, such as more than four intrahepatic and extrahepatic recurrences, after hepatic resection. CONCLUSIONS: MDN index might be a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC, and influence clinical decision-making for individual treatment strategies.