Cilostazol improves the prognosis after hepatectomy in rats with sinusoidal obstruction syndrome.

BACKGROUND AND AIM: Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model. MATERIAL AND METHODS: Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS + CZ (MCT + CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48 h after MCT administration. Postoperative survival rates were evaluated (n = 9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury. RESULTS: The cumulative 10-day postoperative survival rate was significantly higher in the SOS + CZ group than in the SOS group (88.9% vs 33.3%, P = 0.001). Total SOS scores were significantly lower in the SOS + CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS + CZ group than in the SOS group on POD 1 (86.1 ± 8.2% vs 63.8 ± 9.3%, P = 0.003). CONCLUSION: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.

Impact of aging on peribiliary glands in ischemia-reperfusion injury.

BACKGROUND: The detailed mechanisms underlying the development of ischemia-type biliary lesions (ITBLs) in aged donor grafts remain unclear. In the present study we aimed to investigate the impact of aging on the response of the peribiliary gland (PBG) to ischemia-reperfusion injury (IRI) and its temporal changes. METHODS: Experiments were performed using a 90-min partial warm liver ischemia model in male Wistar rats of two age groups: young (7-8 weeks old) and old (52-60 weeks old). Liver tissues were obtained 24, 72, and 168 h after IRI. Histopathological and immunohistochemical assessments of the perihilar bile duct (PHBD), including the PBG, distal to the clip-clamped site were performed. RESULTS: Young rats showed little change in the bile duct tissues after IRI. However, old rats showed an increased PBG volume in the PHBD and marked PBG cell proliferation 24 h after IRI. Bile duct wall thickening with narrowing of the lumen peaked 72 h after IRI. Mucus production and oxidative stress in the PBG were significantly higher in old than in young rats after IRI. These findings showed a trend toward improvement 168 h after IRI. CONCLUSION: Age-dependent differences in the response of the PBG to IRI may be related to differences in ITBL frequency.

Clinicopathological features of cholangiolocarcinoma and impact of tumor heterogeneity on prognosis: A single institution retrospective study.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor.

An Intrahepatic Cholangiocarcinoma with Focal Rhabdoid Features and SMARCA4-Deficiency.

Intrahepatic cholangiocarcinoma with rhabdoid morphology is rare, and only three case reports have been published to date, none of which discuss the genetic changes in the rhabdoid component. We present a case of intrahepatic cholangiocarcinoma with focal rhabdoid features and SMARCA4-deficiency detected using immunohistochemistry. A Japanese man in his 60s without viral hepatitis was diagnosed with an avascular tumor in the liver, measuring 4.4 cm in the greatest dimension. The tumor was mostly composed of moderately differentiated adenocarcinoma, focal poorly differentiated adenocarcinoma, and an undifferentiated rhabdoid component. Immunohistochemical analysis showed an inclusion-like staining pattern for keratin AE1/AE3 and vimentin in the rhabdoid component. BRG1/SMARCA4 was detected in the differentiated component but not in the poorly- and undifferentiated components. Our novel findings reflecting the morphological and genetic heterogeneity of intrahepatic cholangiocarcinoma and will aid the research on drugs targeting the aberrant SWItch/Sucrose NonFermentable complex.

Solitary pleural metastasis in rectal cancer.

Pleural metastasis in rectal cancer is often due to secondary invasion or dissemination from intrapulmonary metastases. To date, there are no reports on solitary pleural metastasis. Here, we report a rare case of lower rectal cancer that recurred as pleural metastasis 4 years after surgical resection of the primary tumor. He was a 65-year-old man who visited our department with an abnormal shadow on his chest X-ray. He had a history of lower rectal cancer and had undergone laparoscopic low anterior resection of the rectum and bilateral lymph node dissection after neoadjuvant chemotherapy. Pathological ypT3N1M0 stage IIIA tumor was diagnosed, and adjuvant chemotherapy was administered. According to the computed tomography scan, a pleural tumor or pulmonary metastasis was suspected. Thoracoscopic partial resection of the lung and a partial pleurectomy were performed for diagnostic and therapeutic purposes. Histopathological examination revealed a highly differentiated tubular adenocarcinoma, consistent with metastatic rectal cancer. The nodule arose from the visceral pleura and invaded the parietal pleura with few malignant cells in the lung parenchyma. The lesion was surgically resected. However, 3 months after the second surgery, tumor recurrence with pleural dissemination was observed, and chemotherapy was initiated.

Closed laparoscopic and endoscopic cooperative surgery for early gastric cancer with difficulty in endoscopic submucosal dissection: a report of three cases.

BACKGROUND: Endoscopic submucosal dissection (ESD) is increasingly applied for early gastric cancer. ESD is a less invasive procedure and could be a radical treatment. However, in some cases, ESD cannot be completed owing to patient or technical factors. In such cases, which could have the potential for curative resection with ESD, standard gastrectomy is excessively invasive. Through closed laparoscopic and endoscopic cooperative surgery (LECS), gastric tumor can be precisely resected without exposing tumor cells to the abdominal cavity. Compared with standard gastrectomy, closed LECS is less invasive for the treatment of early gastric cancer. CASE PRESENTATION: We performed closed LECS for three cases of early gastric cancer after failed ESD. In all three cases, ESD was interrupted owing to technical and patient factors, including perforation, respiratory failure, and carbon dioxide narcosis. All three cases successfully underwent closed LECS with complete tumor resection and showed an uneventful postoperative course. All three patients remain alive and have experienced no complications or recurrence, with a median follow up of 30 (14-30) months. CONCLUSIONS: Closed LECS is less invasive and useful procedure for the treatment of early gastric cancer, particularly in cases with difficulty in ESD.