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1.
Biol Pharm Bull ; 47(6): 1218-1223, 2024.
Article in English | MEDLINE | ID: mdl-38925922

ABSTRACT

Unknown interactions between drugs remain the limiting factor for clinical application of drugs, and the induction and inhibition of drug-metabolizing CYP enzymes are considered the key to examining the drug-drug interaction (DDI). In this study, using human HepaRG cells as an in vitro model system, we analyzed the potential DDI based on the expression levels of CYP3A4 and CYP1A2. Rifampicin and omeprazole, the potent inducers for CYP3A4 and CYP1A2, respectively, induce expression of the corresponding CYP enzymes at both the mRNA and protein levels. We noticed that, in addition to inducing CYP1A2, omeprazole induced CYP3A4 mRNA expression in HepaRG cells. However, unexpectedly, CYP3A4 protein expression levels were not increased after omeprazole treatment. Concurrent administration of rifampicin and omeprazole showed an inhibitory effect of omeprazole on the CYP3A4 protein expression induced by rifampicin, while its mRNA induction remained intact. Cycloheximide chase assay revealed increased CYP3A4 protein degradation in the cells exposed to omeprazole. The data presented here suggest the potential importance of broadening the current DDI examination beyond conventional transcriptional induction and enzyme-activity inhibition tests to include post-translational regulation analysis of CYP enzyme expression.


Subject(s)
Cytochrome P-450 CYP3A , Drug Interactions , Omeprazole , RNA, Messenger , Rifampin , Omeprazole/pharmacology , Humans , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 CYP3A/genetics , Rifampin/pharmacology , RNA, Messenger/metabolism , Cytochrome P-450 CYP3A Inducers/pharmacology , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP1A2/biosynthesis , Cell Line
2.
J Nippon Med Sch ; 91(1): 10-19, 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38233127

ABSTRACT

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.

3.
J Nippon Med Sch ; 91(1): 83-87, 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38072420

ABSTRACT

INTRODUCTION: The spleen is a lymphatic organ that manages immune surveillance of the blood, produces blood cells, and helps filter the blood, remove old blood cells, and fight infection. The normal splenic weight is approximately 65-265 g. This study evaluated spleen volume and segmental volume. METHODS: 121 patients who underwent enhanced CT at our center were analyzed. The spleen was divided into upper, middle, and lower segments according to arterial flow area, and the volume of each segment was measured. Patients were classified into two groups as those with and without liver cirrhosis, and differences in the distribution of the segments in these groups was evaluated. RESULTS: The mean upper, middle, and lower spleen segmental volume ratios were 35.4%, 37.0%, and 27.6%, respectively. In the liver cirrhosis group, the segmental splenic volume ratios for the upper, middle, and lower segments were 34.5%, 38.5%, and 28.0%, respectively, indicating that these ratios remain similar regardless of liver cirrhosis status. CONCLUSION: The present findings on segmental spleen volume are useful for estimating infarction volume in cases of partial splenic arterial embolization.


Subject(s)
Embolization, Therapeutic , Spleen , Humans , Spleen/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/therapy , Vascular Surgical Procedures
4.
Asian J Endosc Surg ; 17(1): e13260, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37941522

ABSTRACT

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.


Subject(s)
Chlamydia Infections , Cholecystitis, Acute , Cholecystitis , Gallbladder Diseases , Female , Humans , Aged, 80 and over , Gallbladder/surgery , Cholecystitis/surgery , Gallbladder Diseases/complications , Gallbladder Diseases/surgery , Chlamydia Infections/complications , Chlamydia Infections/diagnosis
5.
J Int Med Res ; 51(8): 3000605231190967, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37560966

ABSTRACT

OBJECTIVE: The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE. METHODS: Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE. RESULTS: The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%. CONCLUSION: We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.


Subject(s)
Hypersplenism , Splenic Infarction , Humans , Splenic Infarction/diagnostic imaging , Splenic Infarction/therapy , Hypersplenism/therapy , Retrospective Studies , Splenic Artery
6.
Cell Rep ; 42(3): 112157, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36882059

ABSTRACT

Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C-38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5' UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology.


Subject(s)
Circadian Clocks , Mice , Animals , Circadian Clocks/genetics , Circadian Rhythm/physiology , Open Reading Frames/genetics , Body Temperature , Gene Expression Regulation , Mammals/metabolism , Period Circadian Proteins/genetics , Period Circadian Proteins/metabolism
7.
J Nippon Med Sch ; 89(2): 154-160, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35082203

ABSTRACT

Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Combined Modality Therapy , Humans , Japan , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Retrospective Studies , Treatment Outcome
8.
J Nippon Med Sch ; 89(1): 2-8, 2022 Mar 11.
Article in English | MEDLINE | ID: mdl-34526451

ABSTRACT

Simple hepatic cysts are typically saccular, thin-walled masses with fluid-filled epithelial lined cavities. They arise from aberrant bile duct cells that develop during embryonic development. With the development of diagnostic modalities such as ultrasonography (US), CT, and MRI, simple hepatic cysts are frequently detected in clinical examinations. US is the most useful and noninvasive tool for diagnosis of simple hepatic cysts and can usually differentiate simple hepatic cysts from abscesses, hemangiomas, and malignancies. Cysts with irregular walls, septations, calcifications, or daughter cysts on US should be evaluated with enhanced CT or MRI, to differentiate simple hepatic cysts from cystic neoplasms or hydatid cysts. Growth and compression of hepatic cysts cause abdominal discomfort, pain, distension, and dietary symptoms such as nausea, vomiting, a feeling of fullness, and early satiety. Complications of simple hepatic cysts include infection, spontaneous hemorrhage, rupture, and external compression of biliary tree or major vessels. Asymptomatic simple hepatic cysts do not require treatment. Treatment for symptomatic simple hepatic cysts includes percutaneous aspiration, aspiration followed by sclerotherapy, and surgery. The American College of Gastroenterology clinical guidelines recommend laparoscopic fenestration because of its high success rate and low invasiveness. Percutaneous procedures for treatment of simple hepatic cysts are particularly effective for immediate palliation of patient symptoms; however, they are not generally recommended because of the high rate of recurrence. Management of simple hepatic cysts requires correct differentiation from neoplasms and infections, and selection of a reliable treatment.


Subject(s)
Cysts , Liver Diseases , Cysts/complications , Cysts/diagnosis , Cysts/therapy , Humans , Liver Diseases/complications , Liver Diseases/diagnosis , Liver Diseases/therapy , Magnetic Resonance Imaging , Ultrasonography
9.
In Vivo ; 35(4): 2465-2468, 2021.
Article in English | MEDLINE | ID: mdl-34182532

ABSTRACT

BACKGROUND: The number of patients with hemodialysis is increasing increased yearly. Few reports are available on hepatobiliary and gastrointestinal surgery in these patients. PATIENTS AND METHODS: A total of 222 patients who underwent partial liver resection or segmentectomy in our hospital between January 2015 and September 2019 were included in this study. Patients were divided into the hemodialysis group (n=9) and non-hemodialysis group (n=213). RESULTS: No significant difference was observed in postoperative complications between the hemodialysis and non-hemodialysis group. The hemodialysis group had a significantly higher infectious complication rates than the non-hemodialysis group (33.3% vs. 8.0%, p=0.009). In logistic regression analysis, hemodialysis was only a significant risk factor for postoperative infectious complications (OR=5.61, 95% CI=1.12-28.20, p=0.036). CONCLUSION: Liver resections, at least segmentectomy or smaller, is acceptable in patients on hemodialysis. However, these patients may have a higher risk of postoperative infectious complications than other patients.


Subject(s)
Hepatectomy , Liver Neoplasms , Hepatectomy/adverse effects , Humans , Liver/surgery , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Renal Dialysis , Retrospective Studies
10.
J Surg Case Rep ; 2020(6): rjaa134, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32577208

ABSTRACT

Follicular pancreatitis (FP) is characterized by nodular mass composed of lymphoid hyperplasia and fibrosis. We here present radiological and pathological features of three cases of FP. The three patients were middle- or old-aged men, and nodular mass was pointed out at health examination. Computed tomography failed to demonstrate a mass. Magnetic resonance imaging demonstrated a mass in each case. 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) demonstrated two nodular masses with high standardized uptake value (SUV) in two cases and single mass in one case. The pathological examination disclosed two lesions with fibrosis and hyperplastic lymphoid follicles in two cases and one lesion in one case. Masses with high SUV appeared to correspond with the lesions of FP. Compared with the features of FDG-PET images of pancreatic ductal carcinoma, multiple lesions with high SUV favor a diagnosis of FP rather than pancreatic cancer. FDG-PET is useful for the diagnosis of FP.

11.
World J Surg ; 44(9): 3086-3092, 2020 09.
Article in English | MEDLINE | ID: mdl-32394011

ABSTRACT

BACKGROUND: The Pringle maneuver is often used in liver surgery to minimize bleeding during liver transection. Many authors have demonstrated that intermittent use of the Pringle maneuver is safe and effective when performed appropriately. However, some studies have reported that the Pringle maneuver is a significant risk factor for portal vein thrombosis. In this study, we evaluated the effectiveness of portal vein flow after the Pringle maneuver and the impact that massaging the hepatoduodenal ligament after the Pringle maneuver has on portal vein flow. MATERIALS AND METHODS: Patients treated with the Pringle maneuver for hepatectomies performed to treat hepatic disease at our hospital between August 2014 and March 2019 were included in the study (N = 101). We divided these patients into two groups, a massage group and nonmassage group. We measured portal vein blood flow with ultrasonography before and after clamping of the hepatoduodenal ligament. We also evaluated laboratory data after the hepatectomy. RESULTS: Portal vein flow was significantly lower after the Pringle maneuver than before clamping of the hepatoduodenal ligament. The portal vein flow after the Pringle maneuver was improved following massage of the hepatoduodenal ligament. After hepatectomy, serum prothrombin time was significantly higher and serum C-reactive protein was significantly lower in the massage group than in the nonmassage group. CONCLUSION: Massaging the hepatoduodenal ligament after the Pringle maneuver is recommended in order to quickly recover portal vein flow during hepatectomy and to improve coagulability.


Subject(s)
Blood Flow Velocity/physiology , Hepatectomy/methods , Ligaments/physiopathology , Liver Neoplasms/surgery , Massage/methods , Portal Vein/physiopathology , Recovery of Function/physiology , Aged , Female , Humans , Liver/blood supply , Liver/surgery , Liver Neoplasms/diagnosis , Male
12.
J Nippon Med Sch ; 86(4): 222-229, 2019 Sep 03.
Article in English | MEDLINE | ID: mdl-31204379

ABSTRACT

BACKGROUND: Patients with recurrent hepatocellular carcinoma or metastatic liver cancer from colorectal cancer after surgical resection have traditionally been treated with conventional open surgery. However, recent technical advances have facilitated laparoscopic repeat hepatectomy (LapRH), which has advantages over open laparotomy. We describe the results of LapRH at our institution and retrospectively compare short-term outcomes after LapRH and initial laparoscopic partial liver resection (LapPLR). METHODS: From April 2010 through December 2017, 24 patients (16 men, 8 women; median age, 69 years) underwent LRH for cancer recurrence or metastasis after initial partial hepatectomy at our institution. LapRH involved partial hepatectomy in 21 patients and lateral segmentectomy in 3 patients. Short-term outcomes (operative time, intraoperative blood loss, and postoperative hospital stay) for these 24 patients were compared with those for 117 patients who underwent initial LapPLR during the same period. RESULTS: There were no significant differences between the LapPLR and LapRH groups in baseline characteristics, including patient age and underlying disease. No LapRH procedure required conversion to open surgery. There were no statistically significant differences between the groups in median operation time (268 min for LapPLR, 294 min for LapRH; p = 0.55), blood loss (224.0 mL for LapPLR, 77.5 mL for LapRH; p = 0.76), or length of hospital stay (11.0 days for LapPLR, 10.2 days for LapRH; p = 0.83). CONCLUSIONS: LapRH for recurrent liver cancer yielded satisfactory outcomes when compared with those of initial hepatectomy. Further studies are needed, however, to confirm the present results.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Laparoscopy/methods , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Aged , Aged, 80 and over , Blood Loss, Surgical , Female , Humans , Length of Stay , Male , Middle Aged , Operative Time , Reoperation , Time Factors , Treatment Outcome
13.
J Nippon Med Sch ; 86(5): 291-295, 2019 Dec 03.
Article in English | MEDLINE | ID: mdl-31105120

ABSTRACT

The indocyanine green (ICG) fluorescence method is reportedly useful for intraoperative visualization of hepatocellular carcinoma and metastatic liver cancer. Herein, we report the use of an ICG fluorescence navigation system for laparoscopic hepatectomy. The patient was a 73-year-old man with a surgical history of two laparotomies for hepatocellular carcinoma resection. During follow-up at our hospital, abdominal computed tomography revealed recurrence of hepatocellular carcinoma in the lateral area of the liver, after which the patient was hospitalized for surgery. His surgical history indicated that adhesions in the abdominal cavity were likely. We scheduled laparoscopic repeat hepatectomy (LRH) with an ICG fluorescence method in which ICG dye was injected intravenously 2 days before surgery. ICG fluorescence was easily detected intraoperatively. The advantages of the present approach are that it induces pneumoperitoneum and, with laparoscopic magnification, enables good visualization of the surgical field for LRH and clear intraoperative identification of the tumor, thus facilitating LRH. Laparoscopic partial resection of the liver (S3) was successfully performed; the operation time was 197 minutes and bleeding volume was 30 mL. Postoperative course was uneventful and he was discharged on postoperative day 10.


Subject(s)
Hepatectomy , Indocyanine Green/chemistry , Laparoscopy , Reoperation , Aged , Fluorescence , Humans , Intraoperative Care , Male
14.
Nihon Yakurigaku Zasshi ; 153(2): 79-87, 2019.
Article in Japanese | MEDLINE | ID: mdl-30745518

ABSTRACT

Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100 mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100 mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis.


Subject(s)
Antifungal Agents/therapeutic use , Lysine/therapeutic use , Onychomycosis/drug therapy , Triazoles/therapeutic use , Administration, Oral , Antifungal Agents/pharmacokinetics , Capsules , Double-Blind Method , Humans , Lysine/analogs & derivatives , Lysine/pharmacology , Prodrugs/pharmacokinetics , Prodrugs/therapeutic use , Thiazoles/pharmacokinetics , Thiazoles/therapeutic use , Triazoles/pharmacokinetics
15.
Clin Chem Lab Med ; 56(8): 1362-1372, 2018 07 26.
Article in English | MEDLINE | ID: mdl-29648996

ABSTRACT

BACKGROUND: Relatively high mortality and morbidity rates are reported after liver resection (LR). However, the early predictors of complications after LR are not clear. This study was performed to clarify the usefulness of procalcitonin (PCT) for the early prediction of complications after elective LR. METHODS: This observational study included 72 consecutive patients who underwent elective LR from December 2015 to March 2017. Patients were categorized into two groups: those with and without postoperative complications (Clavien-Dindo grade ≥II). The values of postoperative inflammatory markers (white blood cell [WBC] count, C-reactive protein [CRP] and PCT) were compared between the two groups. RESULTS: CRP and PCT were significantly higher in patients with than without complications; however, the WBC count showed no difference within 5 days postoperatively. The maximum area under the receiver operating characteristic curves within 2 days after LR using the WBC count, CRP and PCT were 0.608, 0.697 and 0.860, respectively, PCT had the best predictive ability in the early postoperative period. The PCT level peaked within 2 days postoperatively in 61 patients (85%). The maximum PCT level within 2 days postoperatively (PCT1-2) was significantly higher in patients with than without complications (0.52 vs. 0.19 ng/mL, p<0.001). A cutoff PCT1-2 level of 0.35 ng/mL achieved 80% sensitivity and 83% specificity. In patients without complications, there was no difference in PCT1-2 even when the surgical procedure differed (p=0.935). CONCLUSIONS: PCT1-2 is an early predictive marker after LR and can be similarly used regardless of the LR procedure.


Subject(s)
Liver Neoplasms/surgery , Procalcitonin/blood , Aged , Elective Surgical Procedures , Female , Hepatectomy , Humans , Male , Middle Aged , Postoperative Complications , ROC Curve , Retrospective Studies , Time Factors , Treatment Outcome
16.
Eur J Surg Oncol ; 44(5): 664-669, 2018 05.
Article in English | MEDLINE | ID: mdl-29525467

ABSTRACT

BACKGROUND: The vein that runs between ventral and dorsal Segment 8 is called the anterior fissure vein (AFV). AFV is sometimes needed as a boundary for Subsegmentectomy in Segment 8. The aim of the present study was to investigate the AFV to determine whether the AFV can be used a landmark for subsegmentectomy of the liver at Segment 8. METHODS: We analyzed data from 151 patients who had undergone abdominal computed tomographic (CT) examinations. The position of the AFV is identified by determining whether the AFV drains flows into the proximal, medial, or distal portion of the middle hepatic vein (MHV) or right hepatic vein (RHV). Furthermore, the proximal region is divided into 2 halves; the proximal portion is designated as P1 and the distal portion is designated as P2. RESULTS: The AFV could be identified in 78.8% (119/151) of the patients. The AFV flowed into the MHV in 84.9% of the patients and into the RHV in 15.1%. Among the former, the AFV flowed into the proximal MHV in 69.7% of the patients. CONCLUSIONS: Although the AFV might not be easily identifiable, the AVF can be used to determine the border between the ventral and dorsal portions of Segment 8. The AFV should thus be used as a landmark for Subsegmentectomy.


Subject(s)
Anatomic Landmarks , Hepatectomy/methods , Hepatic Veins/diagnostic imaging , Liver/diagnostic imaging , Portal Vein/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Liver/blood supply , Liver/surgery , Male , Middle Aged , Multidetector Computed Tomography , Young Adult
18.
J Gastroenterol ; 53(2): 291-301, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29143121

ABSTRACT

BACKGROUND: Congenital biliary dilatation (CBD) is a congenital malformation involving both dilatation of the extrahepatic bile duct and pancreaticobiliary maljunction. Persistent reflux of pancreatic juice injures the biliary tract mucosa, resulting in chronic inflammation and higher rates of carcinogenesis in the biliary tract, including the gallbladder. Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal instability due to telomere dysfunction plays an important role in the carcinogenesis of many organs. This study was performed to determine whether excessive shortening of telomeres occurs in the gallbladder mucosa of patients with CBD. METHODS: Resected gallbladders were obtained from 17 patients with CBD, ten patients with cholecystolithiasis without pancreatic juice reflux, and 17 patients with normal gallbladders (controls) (median age of each group of patients: 37, 50, and 53 years, respectively). The telomere lengths of the gallbladder epithelium were measured by quantitative fluorescence in situ hybridization using tissue sections, and the normalized telomere-to-centromere ratio (NTCR) was calculated. RESULTS: The NTCRs in the CBD, cholecystolithiasis, and control groups were 1.24 [interquartile range (IQR) 1.125-1.52], 1.96 (IQR 1.56-2.295), and 1.77 (IQR 1.48-2.53), respectively. The NTCR in the CBD group was significantly smaller than that in the cholecystolithiasis and control groups (p = 0.003 and 0.004, respectively), even in young patients. CONCLUSIONS: Our findings indicate that telomere shortening in the gallbladder mucosa plays an important role in the process of carcinogenesis in patients with CBD. These results support the recommendation of established guidelines for prophylactic surgery in patients with CBD because CBD is a premalignant condition with excessive telomere shortening.


Subject(s)
Bile Ducts, Extrahepatic/abnormalities , Gallbladder/pathology , Pancreatic Ducts/abnormalities , Telomere Shortening , Adult , Bile Ducts, Extrahepatic/diagnostic imaging , Biliary Tract Neoplasms/diagnostic imaging , Biliary Tract Neoplasms/genetics , Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Common Bile Duct/abnormalities , Common Bile Duct/diagnostic imaging , Dilatation, Pathologic/congenital , Dilatation, Pathologic/diagnostic imaging , Dilatation, Pathologic/genetics , Epithelium/pathology , Female , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Pancreatic Ducts/diagnostic imaging , Precancerous Conditions/diagnostic imaging , Precancerous Conditions/genetics , Tomography, X-Ray Computed
19.
In Vivo ; 31(6): 1209-1214, 2017.
Article in English | MEDLINE | ID: mdl-29102948

ABSTRACT

Brain metastases originating from esophageal or gastric cancer are rare, accounting for 2.1-3.3% of all brain tumors registered in Japan. There are no established therapeutic measures for brain metastases, which accordingly have a poor prognosis. We present here a patient who survived for 5 years after surgery and gamma knife treatment of a cerebellar metastasis from esophagogastric adenocarcinoma. The primary gastric cancer was treated by laparotomy with total gastrectomy, splenectomy, and D2 lymphadenectomy. It was diagnosed as a esophagogastric junction Siewert type II tumor, type 3, tub1-2, pT3 (SS), pN1, and stage IIB on histopathological examination of the surgical specimen. Five months postoperatively, a solitary cerebellar metastasis was identified and surgically removed, followed by 20 Gy administered by gamma knife stereotactic radiosurgery; the patient received no subsequent treatment such as chemotherapy. Five years after the primary surgery, there have been no recurrences and the patient has a good quality of life. There are very few case reports of long-term survival after surgical treatment of cerebellar metastases from esophagogastric junction cancer. We report our experience and review published case reports of surgical treatment of brain metastases from gastric cancer.


Subject(s)
Cerebellar Neoplasms/surgery , Esophagogastric Junction/surgery , Radiosurgery , Stomach Neoplasms/surgery , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/secondary , Disease-Free Survival , Esophagogastric Junction/pathology , Female , Humans , Middle Aged , Neoplasm Metastasis , Stomach Neoplasms/pathology
20.
Fundam Clin Pharmacol ; 30(6): 529-536, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27371338

ABSTRACT

We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the phosphorylation of ribosomal protein S6, which is a downstream target of S6 kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 kinase, protects against NMDA-induced retinal injury. Intravitreal injection of NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and neuroinflammatory responses, such as an increase in the number of CD45-positive leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses without affecting phosphorylated S6 levels. These results suggest that PF-4708671 and rapamycin likely protect against NMDA-induced retinal damage via distinct pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 kinase inhibitor.


Subject(s)
Imidazoles/pharmacology , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , N-Methylaspartate/pharmacology , Neuroprotective Agents/pharmacology , Piperazines/pharmacology , Animals , Calcium-Binding Proteins/metabolism , Kidney Diseases/metabolism , Leukocyte Common Antigens/metabolism , Leukocytes/drug effects , Leukocytes/metabolism , Male , Microfilament Proteins/metabolism , Microglia/drug effects , Microglia/metabolism , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Ribosomal Protein S6 Kinases/metabolism , Sirolimus/pharmacology
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