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1.
Front Pharmacol ; 15: 1384733, 2024.
Article in English | MEDLINE | ID: mdl-38799168

ABSTRACT

Background: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). Liquid biomarkers to predict irAE occurrence are urgently needed. We previously developed an ELISA system to specifically detect soluble PD-L1 (sPD-L1) with PD-1-binding capacity (bsPD-L1). Here, we investigated the relationship between sPD-L1 and bsPD-L1 in gastric cancer (GC) and non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 blockade and their association with irAEs. Methods: We examined sPD-L1, bsPD-L1, matrix metalloproteinases (MMPs), and proinflammatory cytokine levels by ELISA in plasma samples from 117 GC patients prior to surgery and 72 NSCLC patients prior to and at 2 months after ICI treatment (anti-PD-1, n = 48; anti-PD-L1, n = 24). In mice treated with anti-PD-1/PD-L1 antibodies (Abs), sPD-L1 levels and localization of Abs were examined by ELISA and immunohistochemistry, respectively. Results:sPD-L1 was detected with higher frequency in GC patients than in NSCLC patients, whereas bsPD-L1 was detected with similar frequencies in GC and NSCLC patients. sPD-L1 levels were correlated with IL-1α, IL-1ß, TNF-α, and IL-6 levels, while bsPD-L1 levels were correlated with MMP13, MMP3, and IFN-γ levels. In NSCLC patients, anti-PD-L1, but not anti-PD-1, treatment increased sPD-L1, which was associated with irAE development, but not with clinical outcomes. In mice, trafficking of anti-PD-L1 Abs to lysosomes in F4/80+ macrophages resulted in sPD-L1 production, which was suppressed by treatment with lysosomal degradation inhibitor chloroquine and macrophage depletion. Conclusion: Anti-PD-L1-mediated lysosomal degradation induces sPD-L1 production, which can serve as an indicator to predict irAE development during anti-PD-L1 treatment.

2.
Front Pharmacol ; 15: 1384731, 2024.
Article in English | MEDLINE | ID: mdl-38774209

ABSTRACT

Background: The tumor microenvironment (TME) impacts the therapeutic efficacy of immune checkpoint inhibitors (ICIs). No liquid biomarkers are available to evaluate TME heterogeneity. Here, we investigated the clinical significance of PD-1-binding soluble PD-L1 (bsPD-L1) in gastric cancer (GC) patients and non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 blockade. Methods: We examined bsPD-L1, matrix metalloproteinases (MMPs), and IFN-γ levels in plasma samples from GC patients (n = 117) prior to surgery and NSCLC patients (n = 72) prior to and 2 months after ICI treatment. We also examined extracellular matrix (ECM) integrity, PD-L1 expression, and T cell infiltration in tumor tissues from 25 GC patients by Elastica Masson-Goldner staining and immunohistochemical staining for PD-L1 and CD3, respectively. Results: bsPD-L1 was detected in 17/117 GC patients and 16/72 NSCLC patients. bsPD-L1 showed strong or moderate correlations with plasma MMP13 or MMP3 levels, respectively, in both GC and NSCLC patients. bsPD-L1 expression in GC was associated with IFN-γ levels and intra-tumoral T cell infiltration, whereas MMP13 levels were associated with loss of ECM integrity, allowing tumor cells to access blood vessels. Plasma MMP3 and MMP13 levels were altered during ICI treatment. Combined bsPD-L1 and MMP status had higher predictive accuracy to identify two patient groups with favorable and poor prognosis than tumor PD-L1 expression: bsPD-L1+MMP13high in GC and bsPD-L1+(MMP3 and MMP13)increased in NSCLC were associated with poor prognosis, whereas bsPD-L1+MMP13low in GC and bsPD-L1+(MMP3 or MMP13)decreased in NSCLC were associated with favorable prognosis. Conclusion: Plasma bsPD-L1 and MMP13 levels indicate T cell response and loss of ECM integrity, respectively, in the TME. The combination of bsPD-L1 and MMPs may represent a non-invasive tool to predict recurrence in GC and the efficacy of ICIs in NSCLC.

3.
Mod Rheumatol ; 33(1): 46-53, 2023 Jan 03.
Article in English | MEDLINE | ID: mdl-35165740

ABSTRACT

OBJECTIVES: The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data. METHODS: We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender, and ages. RESULTS: The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender, and age groups particularly when the number was on the higher side. CONCLUSION: We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Seasons , Retrospective Studies , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/therapeutic use , Methotrexate/therapeutic use
4.
Mod Rheumatol ; 33(6): 1078-1086, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-36308397

ABSTRACT

OBJECTIVES: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS: We counted real incidence rates of OIs for the whole nation from big claims data.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Herpes Zoster , Opportunistic Infections , Pneumonia, Pneumocystis , Tuberculosis , Humans , Aged , Incidence , Retrospective Studies , Pneumonia, Pneumocystis/drug therapy , Arthritis, Rheumatoid/drug therapy , Opportunistic Infections/epidemiology , Tuberculosis/complications , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Herpes Zoster/etiology , Antirheumatic Agents/therapeutic use
5.
Biol Pharm Bull ; 46(2): 237-244, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36477588

ABSTRACT

Community-acquired pneumonia (CAP) is an acute pulmonary parenchymal infection acquired outside the hospital. The utility of blood cultures in inpatients with CAP to reduce mortality and length of hospital stay is controversial. This study aimed to determine the utility of blood cultures on the first day of hospitalization for CAP inpatients and its influence on mortality, length of hospital stay, and antibiotics use. We conducted a fact-finding survey on the implementation of blood culture in inpatients with CAP in Japan. A propensity score (PS)-matched analysis based on the National Database of Health Insurance Claims and Specific Health Check-ups of Japan database was conducted. Overall, 163173 patients were included in the analysis, and PS matching extracted 68104 pairs. The results of the comparison between the PS-matched blood culture group and PS-matched control group were as follows: mortality and length of hospital stay were significantly lower in the PS-matched blood culture group than in the control group. The adjusted odds ratio (OR) (95% confidence interval (CI)) for in-hospital mortality with blood culture test was 0.73 (0.68-0.79). Moreover, for days of antibiotic usage, number of antibiotics used were significantly higher in the PS-matched blood culture group than that in the control group. Our findings indicated that performing a blood culture on the first day of hospitalization for inpatients with CAP was associated with reduced mortality. To our knowledge, this is the largest epidemiological study to assess the utility of blood culture in Japanese inpatients with CAP. This testing method shows potential for application in clinical practice.


Subject(s)
Community-Acquired Infections , Pneumonia , Humans , Blood Culture , Propensity Score , East Asian People , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Pneumonia/drug therapy , Length of Stay , Community-Acquired Infections/drug therapy
6.
Jpn J Clin Oncol ; 53(3): 275-279, 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36546711

ABSTRACT

Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder caused by pathogenic germline variants of mainly SMAD4 or BMPR1A genes. Some patients with JPS, especially with SMAD4 variants, also develop hereditary, hemorrhagic telangiectasia (HHT). HHT is also an autosomal dominant inherited disorder. Herein, we identified a novel germline pathogenic variant of the SMAD4 in a Japanese family with JPS and HHT. A six-base pair deletion in the SMAD4 gene (NM_005359.6:c.1495_1500delTGCATA) was identified in the patients. Two amino acids are deleted from SMAD4 protein (p.Cys499_Ile500del), which are located in MSH2 domain essential for the binding with SMAD3. This is a novel variant that has not been registered in any database surveyed. Amino acid structural analysis predicted significant changes in the secondary and three-dimensional structures in the vicinity of the two amino acids' deletion. The variant is classified as 'Likely Pathogenic' according to the American College of Medical Genetics and Genomics guidelines.


Subject(s)
Intestinal Polyposis , Neoplastic Syndromes, Hereditary , Telangiectasia, Hereditary Hemorrhagic , Humans , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/complications , Smad4 Protein/genetics , East Asian People , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/complications , Intestinal Polyposis/genetics , Intestinal Polyposis/complications , Germ Cells
7.
Anticancer Res ; 42(3): 1599-1605, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35220257

ABSTRACT

BACKGROUND/AIM: The impact of clinical response to taxanes plus ramucirumab (RAM) on overall survival (OS) has not been clarified for advanced gastric cancer (AGC), although this type of therapy is already in use as second-line chemotherapy (CTx). This study aimed to investigate the prognostic impact of the clinical response to taxanes plus ramucirumab (RAM) for AGC patients. PATIENTS AND METHODS: This study included AGC patients treated with paclitaxel (PTX) or nab-paclitaxel (nab-PTX) and RAM. A retrospective analysis of response and survival rates in consecutive medical records of patients was performed. RESULTS: Forty-two patients were enrolled. Median progression-free survival and OS were 5.4 months [95% confidence interval (CI)=4.440-6.361] and 11.8 months (95% CI=8.648-15.019), respectively. In Cox-hazard multivariate analysis, peritoneal metastasis [hazard ratio (HR)=2.830; 95% CI=1.320-6.067; p=0.008], and disease control rate (HR=0.310; 95% CI=0.129-0.741; p=0.008) were independent factors. CONCLUSION: The response to taxanes plus RAM CTx had an impact on the survival of patients with AGC.


Subject(s)
Albumins/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Paclitaxel/therapeutic use , Stomach Neoplasms/drug therapy , Aged , Albumins/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Humans , Male , Medical Records , Paclitaxel/adverse effects , Progression-Free Survival , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Time Factors , Ramucirumab
8.
Mod Rheumatol ; 32(5): 857-865, 2022 Aug 20.
Article in English | MEDLINE | ID: mdl-34907436

ABSTRACT

OBJECTIVES: To describe the real-world prescription and treatment retention of molecular-targeted drugs for rheumatoid arthritis (RA) in Japan. METHODS: A total of 204,416 patients with RA were prescribed at least one of the eight molecular-targeted drugs in 7 years from the National Database of Health Insurance Claims and Specific Health Checkups of Japan covering 98.3% of the Japanese population. The retention rates of each drug as well as head-to-head comparisons were estimated by Kaplan-Meier method. RESULTS: A total of 121,131 RA patients were prescribed any molecular-targeted drug for the first time, while 36,633 uses of molecular-targeted drug were switched from another (switch use). The overall retention rates of molecular-targeted drugs at 12, 36, and 60 months were 0.64, 0.42, and 0.32 for the naïve use and 0.59, 0.40, and 0.31 for the switch use, respectively. Non-tumour necrosis factor (TNF)-inhibitor molecular-targeted drugs, particularly tocilizumab and tofacitinib, had higher retention rates than TNF inhibitors for both naïve and switch uses regardless of the previous drug and showed higher retention rates in head-to-head comparisons between eight molecular-targeted drugs. CONCLUSIONS: Our data reveal that the real-world drug retention is overall lower than previously reported and higher with non-TNF inhibitors than with TNF inhibitors.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Drug Substitution , Humans , Japan/epidemiology , Retrospective Studies , Treatment Outcome
9.
Clin J Gastroenterol ; 14(4): 1053-1059, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34100257

ABSTRACT

Histiocytic sarcoma is a relatively new disease category and the gastrointestinal origin is sporadic. We report a case of a 74-year-old woman who underwent chemotherapy and proximal gastrectomy for extremely rare, advanced gastric histiocytic sarcoma. The resected specimen was subjected to numerous immunostainings to meet the diagnostic criteria of histiocytic sarcoma and was positive for the histiocyte markers' cluster of differentiation 68 and lysozyme. The markers of Langerhans cells, follicular dendritic cells, and myelocyte were all negative. Six reports of surgical resection of histiocytic sarcoma originating in the stomach exist, including our case. We reviewed the clinical course and the histological and immunohistochemical diagnostic features of surgically resected gastric histiocytic sarcoma.


Subject(s)
Histiocytic Sarcoma , Stomach Neoplasms , Aged , Female , Gastrectomy , Histiocytic Sarcoma/drug therapy , Histiocytic Sarcoma/surgery , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery
10.
Cancer Med ; 10(6): 2003-2012, 2021 03.
Article in English | MEDLINE | ID: mdl-33641249

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) detected before surgery disappears after complete surgical resection of the cancer. Residual ctDNA indicates minimal residual disease (MRD), which is a cause of recurrence. The presence of long-fragment circulating cell-free DNA (cfDNA) or methylated cfDNA also implies the presence of cancer. In this study, we evaluated the prognostic value of cfDNA methylation and long-fragment cfDNA concentration in gastric cancer patients undergoing curative surgery METHODS: Ninety-nine gastric cancer patients were included. Peripheral blood samples were collected before and 1 month after surgery. In patients administered chemotherapy, samples were collected before starting chemotherapy. qPCR was performed to detect long- and short-fragment LINE-1. A plasma HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR) assay to determine the concentration of HpaII small fragments was performed using ligation-mediated PCR and HpaII was quantified as the HpaII:MspI ratio to detect methylation levels of cfDNA. RESULTS: Overall survival (OS) of patients with low methylation levels before starting treatment was significantly worse than that of patients with high methylation levels (P = 0.006). In the 90 patients who underwent curative surgery, recurrence-free survival (RFS) and OS of patients with low methylation levels before surgery were worse than those with high methylation levels (P=0.08 and P = 0.11, respectively). RFS and OS of patients with high concentrations of long-fragment LINE-1 after surgery were significantly worse than those with low concentrations of long-fragment LINE-1 (P = 0.009, P = 0.04). CONCLUSIONS: Pre-surgical low methylation levels of LINE-1 are a negative prognostic factor. Post-surgical high concentrations of long-fragment LINE-1 indicate MRD and a high risk of recurrence.


Subject(s)
Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , DNA Methylation , Stomach Neoplasms/blood , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm, Residual , Polymerase Chain Reaction/methods , Prognosis , Stomach Diseases/blood , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery
11.
Clin J Gastroenterol ; 14(2): 494-499, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33512639

ABSTRACT

Reports of gastric collision tumors, comprising adenocarcinoma and gastrointestinal stromal tumor, are extremely rare. Here, we report the case of a 68-year-old male who was diagnosed with a lower-body, moderately differentiated, tubular-type adenocarcinoma and submucosal tumor and underwent an elective D2 distal gastrectomy. The tumor cells of the gastrointestinal stromal tumor were positive for H-caldesmon and CD117, weakly positive for smooth muscle actin and DOG-1, and negative for desmin, S-100 protein, CD31, and AE1/AE3. The tumor had grown into a mixed form of adenocarcinoma and gastrointestinal stromal tumor. Thus, we report the first case of a preoperatively diagnosed collision tumor in the stomach consisting of adenocarcinoma and gastrointestinal stromal tumor.


Subject(s)
Adenocarcinoma , Gastrointestinal Stromal Tumors , Stomach Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/surgery , Humans , Male , Proto-Oncogene Proteins c-kit , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery
12.
Asian J Endosc Surg ; 14(2): 232-240, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32911571

ABSTRACT

INTRODUCTION: Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual-function device in laparoscopic surgery for gastric cancer. METHODS: This single-center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction-forceps using intraoperative video and clinical follow-up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration ("suction access time") and compared this time with that of a conventional surgical setup. RESULTS: In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction-tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01). CONCLUSION: These findings suggest that our new suction-tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879).


Subject(s)
Laparoscopy , Stomach Neoplasms , Gastrectomy , Humans , Japan , Pilot Projects , Stomach Neoplasms/surgery , Suction , Surgical Instruments
13.
J Nippon Med Sch ; 88(3): 242-247, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-32863341

ABSTRACT

Chylous ascites associated with radical resection of gastric cancer is a serious clinical condition. Lymph node dissection is indispensable during gastrectomy for gastric cancer. However, postoperative chylous ascites prolongs the hospital stay and re-operation. There are few reports on this subject. Most cases of chylous ascites resolve without treatment, but the condition can result in substantial morbidity. The definition of chylous ascites is ambiguous and varies in the English literature. In this report, we discuss a case of chylous ascites in a 68-year-old man who underwent distal gastrectomy for early gastric cancer at our hospital. He was admitted 8 months after surgery with a main complaint of abdominal swelling. Abdominal puncture helped to diagnose chylous ascites with marked elevation of triglyceride level. The patient received a hypercaloric infusion through a central line, and octreotide acetate, but did not improve. After assessment of lymph outflow by lymph scintigraphy, surgical ligation of the lymph vessels was performed through laparotomy. The volume of milky-white ascites in the abdominal cavity was 3,000 mL. Macroscopically, the fluid was confirmed as flowing from behind the common hepatic artery. Thus, ligation was performed. Chylous ascites has not recurred at 12 months after the re-operation. In summary, a case of chylous ascites after radical gastrectomy for gastric cancer was successfully treated by surgery. We review and discuss the relevant literature.


Subject(s)
Chylous Ascites/therapy , Fibrin Tissue Adhesive/therapeutic use , Gastrectomy/adverse effects , Lymphatic Vessels/surgery , Stomach Neoplasms/surgery , Aged , Ascites , Chylous Ascites/diagnosis , Chylous Ascites/etiology , Humans , Ligation , Lymphatic Vessels/diagnostic imaging , Male , Neoplasm Recurrence, Local , Radionuclide Imaging , Treatment Outcome
14.
J Nippon Med Sch ; 88(2): 138-144, 2021 May 12.
Article in English | MEDLINE | ID: mdl-32741904

ABSTRACT

Immunoglobulin G4-related disease (IgG4-RD) is a recently characterized illness in which lymphocytes and plasma cells infiltrate various anatomical sites. IgG4-hepatopathy, a manifestation of IgG4-RD, is a broader term covering various patterns of liver injury. The clinical course, including the malignant potential of IgG4-RD, remains unclear. Here we report the first case of secondary hemochromatosis and hepatocellular carcinoma (HCC) developing from IgG4-hepatopathy. A 67-year-old man was admitted to our hospital for treatment of deteriorating glucose tolerance. Blood test results showed hypergammaglobulinemia, especially IgG4. He was readmitted 2 months later with dyspnea due to lung disease and pleural effusion, and elevated transaminase levels. He underwent liver and lung biopsies. IgG4-RD was diagnosed and he was treated with steroid therapy, which improved serum IgG4 levels and imaging abnormalities. A follow-up computed tomography (CT) scan conducted 38 months later revealed a tumor (diameter, 50 mm) in liver segments 7 and 8. The resected specimen revealed HCC and abundant siderosis in the background liver, indicating a diagnosis of hemochromatosis. IgG4-positive cells were scarce, probably because of corticosteroid therapy. In the present case, IgG4-RD was well controlled with prednisolone (PSL) and an immunosuppressive agent, and chronic hepatitis was not severe, even though the patient subsequently developed HCC. However, extensive siderosis consistent with hemochromatosis was unexpectedly noted. These findings suggest that secondary hemochromatosis and HCC developed during IgG4-RD with hepatopathy. We believe this case sheds light on IgG4-RD.


Subject(s)
Carcinoma, Hepatocellular/etiology , Hemochromatosis/etiology , Immunoglobulin G4-Related Disease/complications , Liver Neoplasms/etiology , Humans , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Prednisolone/therapeutic use , Siderosis/etiology
15.
Anticancer Res ; 40(8): 4271-4279, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32727754

ABSTRACT

BACKGROUND/AIM: Skeletal muscle mass (SMM) is often depleted in patients with gastric cancer undergoing gastrectomy. Using a novel method, we evaluated the effect of SMM depletion after gastrectomy on disease prognosis. PATIENTS AND METHODS: The maximum cross-sectional area of the psoas-muscle (MCA-PM) was measured before surgery and at 1 year after in 233 patients with gastric cancer who underwent radical gastrectomy to determine the ratio (MCA-PMR) as an indicator of SMM depletion. RESULTS: The MCA-PMR cutoff value was set at 90%, and patients were divided into the groups with <90% and ≥90%. MCA-PMR <90% was an independent prognostic factor for all patients. In 88 patients who received adjuvant chemotherapy including S-1, the 5-year cancer-specific survival rate was significantly better for those with MCA-PMR ≥90% than for those with MCA-PMR <90% (84.1% vs. 59.1%; p=0.010; hazard ratio=2.974; 95% confidence interval=1.241-7.124). CONCLUSION: SMM depletion after gastrectomy can be measured using the MCA-PMR. This novel measurement can be easily implemented in the clinical setting.


Subject(s)
Gastrectomy/adverse effects , Muscle, Skeletal/pathology , Sarcopenia/etiology , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Sarcopenia/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Survival Rate , Young Adult
16.
Gan To Kagaku Ryoho ; 46(10): 1573-1575, 2019 Oct.
Article in Japanese | MEDLINE | ID: mdl-31631142

ABSTRACT

After undergoing an upper gastrointestinal endoscopy, a 74-year-old woman with anemia was diagnosed with advanced lower gastric cancer. We performed laparotomy and identified the tumor as unresectable because of the direct invasion to the pancreas. S-1 was administered at 60mg/day for 2 weeks followed by 1-week discontinuation. After 6 weeks, we changed the schedule to the same dosage of S-1 for 1 week followed by 2-week discontinuation. CT and endoscopic findings showed complete response after 64weeks of S-1 administration. Since then, S-1 has been maintained at 60mg/day intermittently for 14 days in 7 weeks accordingto the patient's condition. The patient is currently doingwell with a complete response for more than 5 years.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Oxonic Acid/therapeutic use , Stomach Neoplasms , Tegafur/therapeutic use , Aged , Drug Combinations , Female , Humans , Remission Induction , Stomach Neoplasms/drug therapy
17.
Mod Rheumatol ; 29(1): 87-97, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29493381

ABSTRACT

OBJECTIVES: The objective of this study is to compare the effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) by analyzing claims data of 13 Japanese national university hospitals. METHODS: We evaluated 4970 cases of rheumatoid arthritis treated with bDMARDs from the Clinical Information Statistical Analysis database, which has collected and integrated 13 Japanese national university hospitals' claims data for 10 years. We surveyed the medications and calculated the retention rates of bDMARDs using the Kaplan-Meier method and differentiated the effectiveness between the two bDMARDs by comparing the retention rates after switching from one drug to another. RESULTS: Of the 4970 cases, 1364 switched bDMARDs at least once. Tocilizumab (TCZ) reported the highest retention rate, whereas abatacept (ABT) revealed a similar rate compared with only naïve cases. The retention rate curves were higher in cases on TCZ that switched from the other bDMARDs than those in the reversed cases. Following TCZ, ABT and etanercept indicated better results than the other bDMARDs. CONCLUSION: We could compare the effectiveness among bDMARDs by differentiating the retention rates from big claims data. TCZ reported higher retention rates in both naïve and switched cases than other bDMARDs.


Subject(s)
Abatacept , Antibodies, Monoclonal, Humanized , Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Etanercept , Abatacept/administration & dosage , Abatacept/adverse effects , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Big Data , Biological Products/administration & dosage , Biological Products/adverse effects , Databases, Factual , Drug Resistance , Drug Substitution/methods , Drug Substitution/statistics & numerical data , Etanercept/administration & dosage , Etanercept/adverse effects , Female , Humans , Japan/epidemiology , Male , Middle Aged , Treatment Outcome
18.
Surg Case Rep ; 4(1): 100, 2018 Aug 23.
Article in English | MEDLINE | ID: mdl-30141152

ABSTRACT

BACKGROUND: Self-expandable metallic stent placement is a widely performed palliative procedure or bridge to surgery for obstructive colorectal cancer. However, the feasibility of this procedure for large bowel obstruction induced by effective neoadjuvant therapy is unclear. CASE PRESENTATION: We herein report three such cases involving a 61-year-old man who underwent neoadjuvant chemoradiotherapy for lower rectal cancer, a 56-year-old woman who underwent neoadjuvant chemotherapy for lower rectal cancer, and a 63-year-old woman who underwent neoadjuvant chemotherapy for lower rectal cancer. All were emergently hospitalized with large bowel obstruction that developed while undergoing neoadjuvant therapy. Colonoscopy revealed smooth strictures caused by effective neoadjuvant therapy. Self-expandable metallic stents were placed across the obstruction as a bridge to surgery, and laparoscopic low anterior resection was uneventfully performed in all patients. CONCLUSIONS: We successfully treated three patients with large bowel obstruction induced by a good response to neoadjuvant therapy using self-expandable metallic stents as a bridge to surgery. Further studies with larger sample sizes are warranted to assess the feasibility of this strategy.

19.
Asian J Endosc Surg ; 11(2): 169-172, 2018 May.
Article in English | MEDLINE | ID: mdl-28856811

ABSTRACT

Along with the increased use of other laparoscopic procedures, laparoscopic inguinal hernia repair has become widely used because of its minimally invasive nature. Here, we report a case of 66-year-old man who underwent transabdominal preperitoneal laparoscopic hernioplasty and developed hemorrhagic shock on postoperative day 1. CT showed postoperative venous hemorrhage from the retropubic space. Successful hemostasis of the massive hemorrhage was achieved laparoscopically. The origin of the hemorrhage was assumed to be the corona mortis vein, which was slightly injured during the operation. Despite the rarity of this complication, surgeons must be aware of the need to carefully dissect and fix the mesh in the retropubic space to avoid injuring the corona mortis. Laparoscopic hemostasis may be an effective alternative to the open approach.


Subject(s)
Hernia, Inguinal/surgery , Herniorrhaphy , Laparoscopy , Postoperative Hemorrhage/diagnosis , Aged , Hemostasis, Surgical/methods , Herniorrhaphy/methods , Humans , Male , Postoperative Hemorrhage/surgery
20.
Asian J Endosc Surg ; 11(2): 155-159, 2018 May.
Article in English | MEDLINE | ID: mdl-29052338

ABSTRACT

INTRODUCTION: Laparoscopic transabdominal preperitoneal repair (TAPP) is widely accepted in elective inguinal hernioplasty. However, given the scarcity of data, the feasibility and safety of TAPP in strangulated hernia cases have not yet been determined. METHODS: We retrospectively evaluated the data from a consecutive series of 33 patients who had undergone surgery for acute strangulated inguinal hernia associated with suspected visceral ischemic damage by either TAPP (TAPP group, n = 11) or conventional open hernioplasty via the anterior approach (anterior group, n = 22). RESULTS: The TAPP group had a significant longer surgical duration than the anterior group (147 vs 84 min) and relatively less blood loss. Incision and enlargement of the hernial orifice, which enables easy reduction of the strangulated organ, was performed in the last 7 of 11 cases in the TAPP group. The morbidity was lower in the TAPP group, but the difference was not statistically significant (18% vs 23%). The TAPP group had a significantly shorter postoperative hospital stay than the anterior group (7 vs 10 days). CONCLUSION: For surgeons with sufficient knowledge of the anatomy and expertise in reducing the strangulated organ, TAPP for strangulated inguinal hernia is at least comparable to open hernioplasty via the anterior approach in short-term outcomes.


Subject(s)
Hernia, Inguinal/surgery , Herniorrhaphy/methods , Laparoscopy/methods , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Follow-Up Studies , Hernia, Inguinal/pathology , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
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