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.

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.

Assaying ADAMTS13 Activity as a Potential Prognostic Biomarker for Sinusoidal Obstruction Syndrome in Mice.

Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13's plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS.

[Dedifferentiated Liposarcoma Originated from Small Bowel Mesentery Resected under Laparoscopic Surgery-A Case Report].

A 74-year-old woman with severe anemia was presented to our hospital to investigate the cause of the disease. Under investigation, submucosal tumor in the small intestine was suspected. We performed the laparoscopic surgery for resection. The pathological diagnosis was dedifferentiated liposarcoma originated from the small bowel mesentery.

[A Case of Intra-Abdominal Desmoid Tumor after Laparoscopic Resection of Colon Cancer].

An 84-year-old man underwent laparoscopic descending colon resection for colon cancer with stage Ⅰ. Follow-up computed tomography(CT), 18 months after surgery showed a soft tissue density nodular mass, 30 mm in size, in the small intestinal mesentery. The surgical resection of the tumor was performed after a thorough examination. Histopathological examination showed spindle-shaped fibroblasts and abundant collagen fibers. Immunohistochemical staining was negative for c-kit and CD34 and positive for α-SMA and ß-catenin. From the above, this tumor was diagnosed as intra-abdominal desmoid tumor.

[A Case of Cecal Burkitt's Lymphoma with Intussusception].

We report a case of ileocecal intussusception due to Burkitt's lymphoma(BL). A 14-year-old boy was admitted to our hospital for abdominal pain and diarrhea. He was diagnosed an intussusception by the ultrasonography and the CT scan. Laparoscopic ileocecal resection was performed. A diagnosis of BL was made on basis of pathological examination. He was transferred for the chemotherapy on postoperative day 8. We conclude that, if the intussusception associated with malignant lymphoma is assumed from the preoperative findings, we have to keep minimal surgical invasion and start postoperative chemotherapy immediately.

Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.

Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett's esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.

[Examination of Breast Cancer in the Super-Elderly Individuals(85 Years Old and Above)at Our Hospital].

The rate of aging in Japan has currently exceeded 28.1%. Moreover, it is expected that the rate of aging will continue to increase in the future. Under these circumstances, the opportunities to treat breast cancer in the super-elderly individuals are elevating. Here, we summarized and examined the cases who were 85 years or above in age and diagnosed with breast cancer at our hospital during the last 10 years. There were 29 cases(30 breasts), who were all female, with an average age of 89.6 years. Dementia coexisted in 17 cases, and an enlarged mass was the trigger for the discovery in most cases. For breast cancer in super-elderly females, it is necessary to treat it in the right proportion. Moreover, it is considered that the treatment policy should be decided considering the presence or absence of dementia and comorbidities. Also, the treatment regime should be decided upon full consultation with the surroundings, such as family members and long-term care facilities.

[A Case of Radiation Recall Dermatitis That Was Difficult to Distinguish from Inflammatory Breast Recurrence].

The case involved a 51-year-old woman who was diagnosed with Stage Ⅰ right breast cancer(cT1, N0, M0). Partial resection of the right breast and sentinel lymph node biopsy were performed. The histological type was found to be Stage Ⅰ triple-negative medullary carcinoma with pT1c, pN0(sn), and M0. A pituitary tumor was diagnosed after discharge. After removal of the pituitary tumor, whole-breast irradiation was performed. Subsequently, chemotherapy was started. Approximately 5 months after surgery, redness and swelling of the right breast were observed. Inflammatory breast cancer recurrence could not be ruled out by imaging, and skin biopsy was performed. No malignant findings were observed, and the symptoms were considered to indicate radiation recall dermatitis caused by chemotherapy. When chemotherapy was discontinued, the redness of the right breast improved.

[A Case of Local Recurrence 20 Years after Surgery of Ascending Colon Cancer].

The case was a 67-year-old male, who underwent right hemicolectomy+D3 LN resection for ascending colon cancer at the age of 47, and pathological diagnosis was tub1>tub2, T3, N0, M0, ly1, v1, Stage Ⅱa. 20 years after the first surgery, he visited our hospital for intermittent abdominal pain and abdominal fullness. CT scan showed stenosis and wall thickening at the anastomosis of the ileum and colon. When combining the detail examination by upper and lower gastrointestinal endoscopy and PET-CT scan, the tumor was clinically diagnosed asynchronous colon cancer, duodenal invasion. Partial resection of transverse colon and duodenal combined resection was performed. The pathological diagnosis was local recurrence of previous ascending colon cancer. Postoperative adjuvant chemotherapy was performed, but it was discontinued due to poor appetite. Currently, it has not recurred 7 months after the surgery. Recurrences more than 5 years after resection of colorectal cancer are rare, and reports of local recurrence are even rare. A long-term prognosis may be expected for early detection and treatment. Even if more than 5 years passed since the surgery, examination and treatment should be performed with recurrence in mind.

[Stage â £ HER2-Positive Breast Cancer That Showed Complete Response for Over One Year after Discontinuation of Anti-HER2 Therapy-A Case Report].

A 75-year-old woman with a left breast mass on breast cancer screening was referred to our hospital for detailed evaluation. Further examination revealed left breast cancer with metastases to the left axilla, left parasternal region, left supraclavicular fossa, mediastinum, and left hilar lymph nodes, as well as multiple lung metastases. Histopathological evaluation of a needle biopsy specimen revealed invasive ductal carcinoma(scirrhous type), and she was diagnosed with Stage Ⅳ human epidermal growth factor receptor 2(HER2)-positive breast cancer. Following diagnosis, treatment was initiated with trastuzumab, pertuzumab, and docetaxel; however, she developed hypersensitivity to docetaxel and received only trastuzumab and pertuzumab after the second course. We observed a complete response after 3 courses, and treatment was discontinued after 13 courses. She underwent regular evaluation after treatment discontinuation, and a complete response was maintained for 1 year and 6 months. We conclude that combination therapy comprising trastuzumab and pertuzumab was effective for Stage Ⅳ HER2-positive breast cancer and that a complete response could be maintained even after treatment discontinuation.

Pedicled jejunal flap reconstruction for partial duodenectomy: a report of two cases.

Conventional jejunal reconstruction procedures for large duodenal defects include jejunal serosal patch repair and duodenojejunostomy and have some risks of postoperative complications. The pedicled jejunal flap is used for reconstruction following laryngopharyngectomy, esophagectomy and other gastrointestinal surgeries. We report two cases of successful closure of duodenal defects after partial duodenectomies by pedicled jejunal flap reconstruction. Case 1: A 72-year-old man was diagnosed with gastrointestinal stromal tumor by esophagogastroduodenoscopy (EGD), endoscopic ultrasound-guided fine needle aspiration biopsy and computed tomography (CT). Case 2: A 63-year-old woman was diagnosed with early duodenal cancer using EGD and CT. Partial duodenectomy and pedicled jejunal flap reconstruction were performed in both patients. A part of the jejunum was formed into a pedicled flap to fit the duodenal defect and duodenojejunal anastomosis was performed. The patients did not report any postoperative gastrointestinal symptoms or abnormal findings during follow-up EGD or upper gastrointestinal radiography.

A Case of Strangulation Ileus Due to a Low-Grade Appendiceal Mucinous Neoplasm.

BACKGROUND Strangulation ileus is caused by external obstruction to the small bowel, which results in ischemia and loss of bowel peristalsis. Low-grade appendiceal mucinous neoplasm (LAMN) is a low-grade adenocarcinoma that arises in the appendix. LAMN is usually asymptomatic but can present with appendiceal rupture and pseudomyxoma peritonei (PMP). This report is of a rare presentation of LAMN with strangulation ileus in a 92-year-old man. CASE REPORT A 92-year-old man was admitted to the emergency room with sudden onset of lower abdominal pain and abdominal distension. Laboratory investigations showed a leukocytosis with a white blood cell (WBC) count of 14.6×10³/µL with 85.5% neutrophils, blood urea nitrogen (BUN) of 26.6 mg/dL, and serum creatinine of 2.6 mg/dL, consistent with acute renal failure. Arterial blood gas analysis showed lactic acidosis (pH of 7.11) with a base excess of -20.8 mmol/L and lactate of 13.7 mmol/L. Abdominal computed tomography (CT) showed ascites and a dilated obstructed closed loop of the distal ileum associated with an external mass (3.9×2.8 cm). An initial diagnosis was of strangulation ileus due to Meckel's diverticulum. Emergency ileocecal resection was performed. Histopathology showed a low-grade mucinous tumor arising from the mucosa of the appendix, consistent with LAMN. At a 13-month follow-up, the patient was well with no tumor recurrence. CONCLUSIONS This report is of a rare case of LAMN that presented as a surgical emergency with strangulation ileus.

Recurrent biliary dissemination of colon cancer liver metastasis: a case report.

BACKGROUND: Most colorectal cancer liver metastases form nodules within the hepatic parenchyma, and hepatectomy is the only radical treatment for synchronous metastases. There is concern about intrabiliary tumor growth which may affect the surgical margin, resulting in local recurrence after hepatectomy for colorectal cancer liver metastasis; however, there has been no report of the dissemination in the bile duct after hepatectomy. Here, we report an unusual case of biliary dissemination of colorectal cancer that caused recurrent intrabiliary growth after hepatectomy, and discuss the management of intrabiliary metastasis of colorectal cancer. CASE PRESENTATION: A 69-year-old Japanese man underwent treatment for liver dysfunctions 3 years after aortic valve replacement. Computed tomography revealed an enhanced tumor within the hilar bile duct and dilatation of the left hepatic duct, typical of hilar cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography revealed tumor shadow in his bile duct, and the cytology confirmed malignant cells in the bile. We performed extended left hepatectomy with bile duct resection; his postoperative course remained good without acute complications. After 3 months postoperatively, he was readmitted for subacute cholangitis and obstructive jaundice. Immediately, percutaneous transhepatic cholangiography drainage was performed, followed by cholangiography that exhibited intrabiliary tumor growth in the remnant liver. On immunohistochemical examination, tumor cells were positive for cytokeratin 20 and CDX2 but negative for cytokeratin 7. Then, computed tomography revealed an enhanced tumor-like lesion at the descending colon. After 3 months, left hemicolectomy was performed. Meanwhile, the percutaneous transhepatic cholangiography drainage fluid turned bloody, which was considered to be bleeding from a residual bile duct tumor. Accordingly, radiotherapy was initiated to prevent tumor bleeding around the hilar bile duct, but, unfortunately, the effects were short-lived, and cholangitis rebooted after 1 month leading to our patient's death due to septic liver failure. Autopsy revealed a remnant tumor in the bile duct, but no noticeable nodular metastasis was observed, except for a single small metastasis in the lower lobe of the left lung. CONCLUSIONS: The intrabiliary growth of metastatic colorectal cancer mimics cholangiocarcinoma occasionally. To date, as the effect of chemotherapy or radiotherapy remains uncertain, the complete resection of a bile duct tumor is the only method which could result in a better prognosis.

Adenocarcinoma in a Blind Loop of the Ileum 53 Years After an Ileotransversostomy Procedure.

BACKGROUND Primary small bowel cancer is a rare malignancy; the common histopathological types are carcinoid and adenocarcinoma. Inflammatory bowel diseases and familial adenomatous polyposis are known risk factors for small bowel cancer. Additionally, cases of surgery-induced small bowel adenocarcinoma are sometimes reported after ileostomy. CASE REPORT A 84-year-old woman, who had undergone ileotransversostomy for intestinal obstruction due to postoperative adhesion following appendectomy at the age of 31 years, was referred to our hospital for further examination after experiencing abdominal pain in the right lower quadrant for 2 weeks. Laboratory data showed elevated serum levels of carcinoembryonic antigen (CEA, 102.9 ng/ml) and carbohydrate antigen 19-9 (CA19-9, 104 U/ml). Enhanced computed tomography (CT) revealed a 10-cm mass in the terminal ileum and a distention of the ileum and colon in the blind loop, with retention of feces. The patient was suspected of having ileal cancer by preoperative examination; therefore, right hemicolectomy with en bloc resection was performed. The tumor was histopathologically diagnosed as a well-differentiated and mucinous adenocarcinoma of the ileum. At over 12 months after surgery, tumor recurrence had not been observed. CONCLUSIONS Difficulties in diagnosis can cause delays in treatment and lead to poor prognosis, mainly because tumors in the small bowel rarely cause clinical symptoms. Adenocarcinoma of the ileum should be considered in postoperative patients with ileotransversostomy.

S-shape spring sensor: Sensing specific low-frequency vibration by energy harvesting.

We have developed a Si-based microelectromechanical systems sensor with high sensitivity for specific low-frequency vibration-sensing and energy-harvesting applications. The low-frequency vibration sensor contains a disk proof mass attached to two or three lead zirconate titanate (PZT) S-shape spring flexures. To obtain a faster and less expensive prototype, the design and optimization of the sensor structure are studied via finite-element method analysis. To validate the sensor structure to detect low-frequency vibration, the effects of geometrical dimensions, including the width and diameter of the S-shape spring of the proof mass, were analyzed and measured. The functional features, including the mechanical property and electrical performance of the vibration sensor, were evaluated. The results demonstrated that a very low resonant frequency of <11 Hz and a reasonably high voltage output of 7.5 mV at acceleration of >0.2g can be typically achieved. Given a low-frequency vibration sensor with ideal performance and mass fabrication, many advanced civilian and industrial applications can be possibly realized.

Vertical silicon waveguide coupler bent by ion implantation.

We propose and demonstrate that vertically curved waveguides (VCWs) enable vertical coupling between silicon wire waveguides and optical fibers with low wavelength dependence and polarization dependence for wide telecommunication wavelength band light. To bend these VCWs, we implanted silicon ions into silicon wire cantilevers from the vertical direction. The internal stress distribution that was induced by ion implantation drove the bending force, and we achieved vertical bending of the waveguides, with curvature radii ranging from 3 to 25 µm. At a radius of curvature of 6 µm, we obtained a coupling loss of 3 dB using a lens fiber.

Spot-size converter with a SiO(2) spacer layer between tapered Si and SiON waveguides for fiber-to-chip coupling.

We experimentally demonstrate low-loss and polarization-insensitive fiber-to-chip coupling spot-size converters (SSCs) comprised of a three dimensionally tapered Si wire waveguide, a SiON secondary waveguide, and a SiO(2) spacer inserted between them. Fabricated SSCs with the SiO(2) spacer exhibit fiber-to-chip coupling loss of 1.5 dB/facet for both the quasi-TE and TM modes and a small wavelength dependence in the C- and L-band regions. The SiON secondary waveguide is present only around the SSC region, which significantly suppresses the influence of the well-known N-H absorption of plasma-deposited SiON at around 1510 nm.