Publications by authors named "Yosuke Shimizu"

111 Publications

Clinical complete response after nivolumab administered as a third-line treatment for unresectable advanced gastric cancer with peritoneal dissemination: A case report.

Int J Surg Case Rep 2021 Jul 30;84:106161. Epub 2021 Jun 30.

Department of Surgery, National Hospital Organization, Kure Medical Center Chugoku Cancer Center, Japan; Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.

Introduction And Importance: Nivolumab, which is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has been recommended as a third-line treatment based on the results of the ATTRACTION-2 study involving patients with unresectable advanced gastric cancer.

Case Presentation: A 69 year-old woman was referred to our department with a diagnosis of gastric cancer based on an upper gastrointestinal endoscopy during a medical examination. The endoscopy, along with various tests, helped establish a diagnosis of unresectable advanced gastric cancer (cT4aN3aM1P1c, cStage IV) with peritoneal dissemination. The first and second-line chemotherapy administered was S-1 plus oxaliplatin followed by ramucirumab and nab-paclitaxel, respectively. In this case, the disease was evaluated as progressive disease due to increased peritoneal dissemination. Nivolumab was administered as the third-line treatment. The patient developed interstitial pneumonia after nine courses of nivolumab, for which chemotherapy was discontinued and prednisolone treatment was initiated. The patient had a complete response to treatment endoscopically, 9 months after the last administration of nivolumab. After that, there was no recurrence of the cancer, despite there being no treatment for 5 months.

Clinical Discussion: It was suggested that the therapeutic effect of nivolumab could be maintained for a long period after discontinuation of its administration. In addition, a correlation has been reported between the treatment efficacy and immune-related adverse events associated with nivolumab.

Conclusions: The synergistic effect of the sustained effect of nivolumab and later-line treatment may contribute to the prolongation of survival after discontinuation of nivolumab in patients who are refractory or intolerant to treatment.
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http://dx.doi.org/10.1016/j.ijscr.2021.106161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264597PMC
July 2021

[A Case of Ureteral Metastasis from Prostate Cancer].

Hinyokika Kiyo 2021 Apr;67(4):171-176

The Department of Urology, Kobe City Nishi-Kobe Medical Center.

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5+5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.
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http://dx.doi.org/10.14989/ActaUrolJap_67_4_171DOI Listing
April 2021

Annexin A10 Expression Is Associated With Poor Prognosis in Small Bowel Adenocarcinoma.

Anticancer Res 2021 Mar;41(3):1349-1355

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Background/aim: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA.

Materials And Methods: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors.

Results: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis.

Conclusion: ANXA10 could be a new prognostic biomarker for SBA.
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http://dx.doi.org/10.21873/anticanres.14892DOI Listing
March 2021

Laparoscopic resection for a large gastrointestinal stromal tumor (GIST) with diaphragm invasion following preoperative imatinib treatment: A case report.

Int J Surg Case Rep 2021 Apr 5;81:105727. Epub 2021 Mar 5.

Department of Surgery, National Hospital Organization, Kure Medical Center, Chugoku Cancer Center, 3-1, Aoyama, Kure City, Hiroshima 737-0023, Japan; Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Introduction: Neoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment.

Presentation Of Case: A 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted.

Discussion: Neoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery.

Conclusions: This is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.
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http://dx.doi.org/10.1016/j.ijscr.2021.105727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957117PMC
April 2021

Effect of optimal neoadjuvant chemotherapy on oncological outcomes of locally advanced bladder cancer with laparoscopic radical cystectomy: A matched-pair analysis in a multicenter cohort.

Int J Urol 2021 06 7;28(6):656-664. Epub 2021 Mar 7.

Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: To assess the effect of optimal neoadjuvant chemotherapy of at least three cycles of cisplatin-based regimen on oncological outcomes of clinical stage T3 or higher bladder cancer treated with laparoscopic radical cystectomy.

Methods: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. The outcomes of patients who received optimal neoadjuvant chemotherapy and those who did not receive neoadjuvant chemotherapy were compared using propensity score matching in clinical stage T3-4 or T2 cohorts, separately.

Results: Of the 455 patients screened, matched pairs of 54 patients in the clinical T3-4 cohort and 68 patients in the clinical T2 cohort were finally analyzed. In the cT3-4 cohort, the 5-year overall survival (78% vs 41%; P = 0.014), cancer-specific survival (81% vs 44%; P = 0.008) and recurrence-free survival (71% vs 53%; P = 0.049) were significantly higher in the optimal neoadjuvant chemotherapy group than in the no neoadjuvant chemotherapy group; no significant survival difference was shown between the two groups in the cT2 cohort. In the cT3-4 cohort, the incidence of local recurrence (4% vs 26%; P = 0.025) and abdominal or intrapelvic recurrence, including peritoneal carcinomatosis (7% vs 30%; P = 0.038), was significantly lower in the optimal neoadjuvant chemotherapy group.

Conclusions: Administration of optimal neoadjuvant chemotherapy has a significant survival benefit. It decreases the incidence of local and atypical recurrence patterns in patients with clinical stage T3 or higher locally advanced bladder cancer undergoing laparoscopic radical cystectomy.
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http://dx.doi.org/10.1111/iju.14533DOI Listing
June 2021

[MSI-H Small Bowel Cancer with Peritoneal Dissemination Successfully Treated with Pembrolizumab-A Case Report].

Gan To Kagaku Ryoho 2020 Dec;47(13):2009-2011

Dept. of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center.

A 52-year-old man was diagnosed with small bowel adenocarcinoma(T4aN1M0, Stage ⅢA, according to the Japanese colorectal cancer classification)and treated with partial resection of the small bowel in June 2014. He also received adjuvant chemotherapy(XELOX: 8 courses)after surgery. Three and a half years after the operation, peritoneal dissemination recurred, and he received bevacizumab plus XELOX therapy. The regimen was adjusted to a total of 11 courses because of the disease progression. The primary lesion showed MSI-H. The patient was started on pembrolizumab therapy in April 2019. The tumor responded well to pembrolizumab(maximum therapeutic effect: PR, 31% reduction), but a new lesion appeared 6 months after the start of this regimen. He continued pembrolizumab therapy for 14 months without adverse events since it appeared to be clinically effective. Although MSI-H small bowel cancers are rare, accurate screening is essential to not miss the opportunity to administer pembrolizumab.
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December 2020

Intramucosal Poorly Differentiated Adenocarcinomas Detected in a Patient with Long-Standing Ulcerative Colitis.

Case Rep Oncol 2020 Sep-Dec;13(3):1176-1184. Epub 2020 Sep 28.

Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.

We report a case of long-standing ulcerative colitis with intramucosal well- and poorly differentiated adenocarcinomas detected over a 6-month duration. A Japanese man in his sixties with a 31-year history of ulcerative colitis had a 1.1-cm-sized intramucosal well-differentiated tubular adenocarcinoma in the rectum resected by endoscopic submucosal dissection. At the follow-up colonoscopy, a biopsy near the endoscopic submucosal dissection scar revealed poorly differentiated adenocarcinoma, and a total proctocolectomy was performed 6 months after the endoscopic submucosal dissection. The whole colorectal pathological exam showed 2 flat foci of intramucosal poorly differentiated adenocarcinoma, 4 and 2 mm in size each, near the endoscopic submucosal dissection scar in the rectum, and an increased number of Paneth cells, thickened muscularis mucosa, and widening of the distance between the gland base and muscularis mucosa in the transverse colon to the rectum. Adenocarcinomas were not found in areas where architecturally severe changes of the mucosa or the highest number of Paneth cells proliferation were detected. Multiple biopsies using magnifying narrow band imaging or crystal violet staining around the initial high-grade dysplasia or intramucosal adenocarcinoma were effective to find other lesions, such as poorly differentiated adenocarcinoma foci in the mucosa in a long-standing ulcerative colitis patient.
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http://dx.doi.org/10.1159/000510305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590757PMC
September 2020

Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy.

J Control Release 2021 01 22;329:1090-1101. Epub 2020 Oct 22.

Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Mesenchymal stem cells (MSCs) have a tumor-homing ability-they accumulate inside tumors after systemic injection, and may thus be useful as carriers for tumor-targeting therapy. To use MSCs effectively as an anti-cancer therapy, they must first be functionalized with a large amount of anti-cancer drugs without causing any significant changes to their tumor-tropism. In the present study, we attempted to modify the cell surface of MSCs with doxorubicin-loaded liposomes (DOX-Lips), using the avidin-biotin complex method, and evaluated delivery efficiency and anti-tumor efficacy of DOX-Lip-modified MSCs. The amount of DOX in DOX-Lip-modified C3H10T1/2 cells, a murine mesenchymal stem cell line, was approximately 21.5 pg per cell, with no significant changes to the tumor-tropism of C3H10T1/2 cells. Notably, DOX-Lip-modified C3H10T1/2 cells significantly suppressed the proliferation of firefly luciferase-expressing murine colon adenocarcinoma colon26/fluc cells, compared to DOX-Lips alone. Fluorescent DOX accumulated at the cell contact surface and inside green fluorescence protein-expressing colon26 (colon26/GFP) in co-cultures of DOX-Lip-modified C3H10T1/2 and colon26/GFP cells. This localized distribution was not observed when only DOX-Lips was added to colon26/GFP cells. These results suggest that DOX-Lips are efficiently delivered from DOX-Lip-modified C3H10T1/2 cells to the neighboring colon26 cells. Furthermore, DOX-Lip-modified C3H10T1/2 cells suppressed tumor growth in subcutaneous tumor-bearing mice, and in a lung metastasis mouse model. Taken together, these results indicate that the intercellular delivery of DOX may be enhanced using DOX-Lip-modified MSCs as an efficient carrier system for targeted tumor therapy.
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http://dx.doi.org/10.1016/j.jconrel.2020.10.037DOI Listing
January 2021

A case of Turcot's syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report.

BMC Med Genet 2020 07 1;21(1):141. Epub 2020 Jul 1.

Department of Surgery, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure City, Hiroshima, 737-0023, Japan.

Background: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes.

Case Presentation: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis.

Conclusion: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.
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http://dx.doi.org/10.1186/s12881-020-01079-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345515PMC
July 2020

Gastric adenocarcinoma appearance in leiomyoma: A case report.

Int J Surg Case Rep 2020 29;71:327-330. Epub 2020 May 29.

Department of Surgery, National Hospital Organization, Kure Medical Center, Chugoku Cancer Center, 3-1 Aoyama, Kure City, Hiroshima, 737-0023, Japan; Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Introduction: We experienced an extremely rare case of gastric adenocarcinoma wrapped by leiomyoma.

Presentation Of Case: A 65-year-old man had an abnormality (filling defect) of the upper gastrointestinal series in his first medical checkup five years prior. Esophagogastroduodenoscopy detected a 10 mm submucosal tumor-like lesion in the greater curvature of the upper gastric remnant body. Despite repeated biopsy from the lesion, there was no sign of malignancy. A delle was observed on the top of the tumor at another visit five year after the first and a biopsy specimen revealed poorly differentiated adenocarcinoma. Therefore, laparoscopic gastrectomy was performed. Histological assessment revealed a 28 × 22 mm elevated lesion with a slight depression. Microscopically, papillary adenocarcinoma was observed at the submucosa with a solitary heterotopic gastric gland adjacent to the lesion. The final diagnosis was papillary adenocarcinoma arising from a solitary heterotopic gastric gland in the leiomyoma. No recurrence has occurred during a follow-up of two and a half years after surgery.

Conclusions: This is the first report of gastric adenocarcinoma arising from a submucosal tumor.
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http://dx.doi.org/10.1016/j.ijscr.2020.05.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265051PMC
May 2020

[A Case of Sigmoid Colon Cancer Recurrence at the Hand-Sewn Anastomosis Site Originated from Tumor Implantation].

Gan To Kagaku Ryoho 2020 Mar;47(3):475-477

Dept. of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center.

We report a case of anastomotic recurrence following laparoscopic sigmoidectomy with hand-sewn anastomosis, which was attributable to the implantation of exfoliated cancer cells. A 78-year-old man diagnosed with early colon cancer underwent endoscopic submucosal dissection(ESD); however, ESD was suspended due to infiltrated muscle fibers. Subsequently, he underwent laparoscopic sigmoidectomy with hand-sewn anastomosis, accompanied by D3 lymph node dissection. Histopathological findings revealed a well-differentiated tubular adenocarcinoma, pT2(MP), tub1>tub2>por2, ly0, v1, PM0, DM0, RM0, N0M0, pStage Ⅰ. The follow-up CT 6 months after surgery, showed enhanced wall thickening and irregular surface of the sigmoid colon. Colonoscopy revealed a type 2 tumor located on the anastomotic line. Based on the diagnosis of anastomotic recurrence, the patient underwent partial colectomy. Histopathological findings were similar to those of the primary tumor and suggested implantation of exfoliated cancer cells as the origin of anastomotic recurrence. Cancer cells had infiltrated all layers. In conclusion, we recommend the performance of appropriate operative procedures to prevent anastomotic recurrence, such as the cleaning of the anastomosed intestinal tract. Careful follow-up in colon cancer patients is of the utmost importance and the risk of anastomotic recurrence should always be considered.
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March 2020

Perioperative and oncological outcomes of laparoscopic radical cystectomy with intracorporeal versus extracorporeal ileal conduit: A matched-pair comparison in a multicenter cohort in Japan.

Int J Urol 2020 Jun 20;27(6):559-565. Epub 2020 Apr 20.

Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: To compare the perioperative and oncological outcomes of pure laparoscopic intracorporeal ileal conduit urinary diversion versus extracorporeal ileal conduit urinary diversion after laparoscopic radical cystectomy for bladder cancer in a multicenter cohort in Japan.

Method: A total of 455 patients who underwent laparoscopic radical cystectomy carried out at 10 institutions were included in this retrospective study. The perioperative data of the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups were compared using the propensity score matching method. The Kaplan-Meier curves were obtained to elucidate time to ureteroenteric stricture, reoperation, recurrence and survival.

Results: In total, 72 matched pairs were evaluated for the final analysis. The median follow-up period was 28 and 23 months in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively. The operative time in the intracorporeal ileal conduit urinary diversion group was approximately 1 h longer than that in the extracorporeal ileal conduit urinary diversion group. The early and late postoperative complication rates were similar in both groups, except for the reduced wound-related complication rates in the intracorporeal ileal conduit urinary diversion group. The median days to regular oral food intake were 4 and 5 days in the intracorporeal ileal conduit urinary diversion and extracorporeal ileal conduit urinary diversion groups, respectively (P = 0.014). No significant difference was noted in the occurrence of ureteroenteric strictures and reoperation rate. Furthermore, recurrence-free, cancer-specific, and overall survival rates and recurrence patterns did not significantly differ.

Conclusions: Laparoscopic intracorporeal ileal conduit urinary diversion is a safe, feasible and reproducible procedure with similar postoperative complication rates, ureteroenteric stricture rate and oncological outcomes when compared with extracorporeal ileal conduit urinary diversion, but faster postoperative bowel recovery and decreased wound-related complication rates.
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http://dx.doi.org/10.1111/iju.14245DOI Listing
June 2020

Comparison of single- and multiple-dose cefazolin as prophylaxis for transurethral enucleation of prostate: A multicenter, prospective, randomized controlled trial by the Japanese Research Group for Urinary Tract Infection.

Int J Urol 2020 Mar 21;27(3):244-248. Epub 2020 Jan 21.

Department of Urology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Objectives: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia.

Methods: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018.

Results: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00).

Conclusions: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.
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http://dx.doi.org/10.1111/iju.14181DOI Listing
March 2020

Oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer: A Japanese multicenter cohort.

Int J Urol 2020 Mar 16;27(3):250-256. Epub 2020 Jan 16.

Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: To investigate oncological outcomes and recurrence patterns after laparoscopic radical cystectomy for bladder cancer in a Japanese multicenter cohort, and to explore the risk factors associated with recurrences due to tumor dissemination.

Method: Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. Multivariate analyses were carried out to identify the clinical parameters associated with overall recurrences together with specific recurrence types. Kaplan-Meier curves were created to elucidate time to recurrence and survival.

Results: A total of 411 patients were included after the final analysis. Postoperative pathology was T2 or higher in 196 patients (48%), and lymph node metastasis was present in 46 patients (11%). The median follow-up period was 23 months, and the 2-year recurrence-free and cancer-specific survival rates were 71.0% and 84.7%, respectively. The recurrence sites involved distant metastasis in 75 patients (18%), local recurrence in 52 patients (13%) and urinary tract recurrence in eight patients (2%). When local recurrence at the cystectomy bed (28 patients; 7%) and abdominal recurrence including peritoneal carcinomatosis or port site recurrence (17 patients; 4%), which might be caused by tumor dissemination, were combined into a single group, prolonged surgical time was a significant risk factor, in addition to high pathological stage (T3-4 and/or positive lymph nodes), positive surgical margins, and variant histology by both univariate and multivariate analyses.

Conclusions: Our study findings suggest that recurrences after laparoscopic radical cystectomy might be caused by tumor dissemination, and attention should be paid to avoid prolonged surgical time in laparoscopic radical cystectomy.
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http://dx.doi.org/10.1111/iju.14182DOI Listing
March 2020

[The Safety of Laparoscopic Radical Cystectomy during Initial Phases in a Japanese Multicenter Cohort].

Hinyokika Kiyo 2019 Nov;65(11):439-444

The Department of Urology, Graduate School of Medicine, Kyoto University.

We evaluated the safety of laparoscopic radical cystectomy (LRC) during initial phases and its learning curve in a Japanese multicenter cohort by studying 436 patients who underwent LRC with no robot assistance at 10 institutions in Japan. We divided the patients into three groups according to cumulative surgical volume at each institution (first 10 cases, 11-30 cases, after 31 cases in each institution), and compared perioperative and pathologic variables among the three groups. The first, second, and third groups included 100, 166, 170 patients, respectively. The preoperative variables were similar in the three groups except for the rate of neoadjuvant chemotherapy. The methods of LRC procedure, such as urinary diversion, the extent of lymph node dissection, and concomitant urethrectomy or nephroureterectomy, were similar in the three groups. Mean operative time was 629, 562 and 531 minutes, respectively, and mean blood loss was 755, 650 and 435 ml, respectively. Both values decreased over time with the institution's experience. There was no significant difference among the three groups in the rate of positive surgical margin, the number of retrieved lymph nodes, and the rate of intra- and postoperative complications. LRC was safely performed during initial phases with an acceptable complication rate and without compromising oncological results, although operative time was longer and blood loss increased.
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http://dx.doi.org/10.14989/ActaUrolJap_65_11_439DOI Listing
November 2019

Feasibility and efficacy of repeat laparoscopic liver resection for recurrent hepatocellular carcinoma.

Surg Endosc 2020 10 18;34(10):4574-4581. Epub 2019 Dec 18.

Department of Surgery, Kure Medical Center/Chugoku Cancer Center, 3-1 Aoyama, Kure, Hiroshima, 737-0023, Japan.

Background: Repeat hepatectomy is an acceptable treatment for recurrent hepatocellular carcinoma (HCC). However, repeat laparoscopic liver resection (LLR) has not been widely adopted due to its technical difficulty. This study aimed to assess the feasibility and efficacy of repeat LLR compared with repeat open liver resection (OLR) for recurrent HCC.

Methods: We performed 42 repeat OLR and 30 repeat LLR for cases of recurrent HCC between January 2007 and March 2018. This study retrospectively compared the patients' clinicopathological characteristics and operative and short-term outcomes including surgical time, intraoperative blood loss, duration of hospital stay, and postoperative complications between the two groups.

Results: There were no significant differences in patient characteristics between the two groups except in terms of Child-Pugh grade. The repeat LLR group had lower median intraoperative blood loss (100 mL vs. 435 mL; P = 0.001) and shorter median postoperative hospital stay (10 days vs. 14.5 days; P = 0.002). The other results including postoperative complications were comparable between the two groups. Further, comparison of two subpopulations of the repeat LLR group stratified by previous hepatectomy type (open or laparoscopic) or tumor location (segments 7 and 8 or other) revealed no significant differences in the postoperative clinical characteristics between them, although the morbidity rate tended to be higher in patients who underwent open hepatectomy for primary HCC than in patients who underwent laparoscopic hepatectomy.

Conclusions: Repeat LLR for recurrent HCC is feasible and useful with good short-term outcomes although an appropriate patient selection seems to be necessary.
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http://dx.doi.org/10.1007/s00464-019-07246-3DOI Listing
October 2020

A case of hepatic pseudolymphoma in a patient with primary biliary cirrhosis.

Clin Case Rep 2019 Oct 20;7(10):1863-1869. Epub 2019 Aug 20.

Department of Surgery National Hospital Organization Kure Medical Center Chugoku cancer center Kure Japan.

Hepatic pseudolymphoma is a very rare benign reactive lymphoid hyperplasia associated with autoimmunity and chronic inflammatory liver diseases such as primary biliary cirrhosis and may mimic hepatocellular carcinoma. This diagnosis should be suspected in female with a suspicious single tumor. Close monitoring is needed in view of its premalignant nature.
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http://dx.doi.org/10.1002/ccr3.2378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787817PMC
October 2019

A Case of Advanced Gastric Cancer with Peritoneal Metastasis Treated Successfully with Nivolumab.

Case Rep Oncol 2019 May-Aug;12(2):523-528. Epub 2019 Jul 16.

Department of Surgery, National Hospital Organization Kure Medical Center, Kure City, Japan.

Peritoneal metastasis (PM) is detected in 14% of gastric cancers at the time of initial diagnosis, with a median survival time of 4 months. A 66-year-old woman diagnosed with cT4a(SE) N2M1(LYN) cStage IV was treated with three lines of chemotherapy for a year. During the third line of chemotherapy, computed tomography (CT) scan revealed a large amount of ascites, periportal collar sign, and bilateral ureteral stenosis owing to PM. The tumor biomarkers (CEA and CA 19-9) remained elevated similar to the initial levels. The patient was administered 3 mg/kg nivolumab intravenously biweekly as the fourth line of chemotherapy. Three months after the nivolumab treatment, gastroscopy revealed an extreme reduction of the tumor size, while CT scan revealed the absence of ascites and a well-controlled tumor. There was no immune-related adverse event with nivolumab during and after the treatment, and performance status improved to 0. The patient has been alive for about 2.5 years since her first visit with her sixth line of chemotherapy (docetaxel). We report a case of advanced gastric cancer with PM that was treated successfully with nivolumab.
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http://dx.doi.org/10.1159/000501717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696775PMC
July 2019

[A Case of Isolated Peritoneal Metastasis from Prostate Cancer].

Hinyokika Kiyo 2019 May;65(5):175-179

The Department of Urology, Kobe City Nishi-Kobe Medical Center.

Peritoneal metastasis of prostate cancer is extremely rare, with only a few cases reported. A 78-yearold male patient was introduced to our hospital presenting with a prostate-specific antigen (PSA) level of 94.0 ng/ml at examination. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, with a Gleasonscore of 9 (5+4) at cT3bN0M0. Intensity-modulated radiation therapy was performed after 6 months of combined-androgen blockade (CAB) therapy. Twenty-one months later, several lymph node metastases were observed. With the resumptionof CAB therapy, PSA levels dropped and the multiple lymph node metastasis disappeared ; however, peritoneal metastasis was observed after 43 months. We performed a laparoscopic biopsy and our diagnosis after pathological evaluation was metastasis of the prostate cancer. He was treated with Enzalutamide.
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http://dx.doi.org/10.14989/ActaUrolJap_65_5_175DOI Listing
May 2019

Laproscopic treatment for small bowel bleeding after detection by double-balloon endoscopy: A case report.

Int J Surg Case Rep 2019 10;59:63-65. Epub 2019 May 10.

Department of Surgery, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyama-cho, Kure city, Hiroshima, 737-0023, Japan; Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Electronic address:

Introduction: The frequency of small bowel bleeding is relatively low and the process for the diagnosis and treaVtment remains difficult. Here, we report a case of massive small bowel bleeding due to arteriovenous malformation (AVM), treated by a combination of double-balloon endoscopy and laparoscopic resection.

Presentation Of Case: A 59-year-old man was admitted to our hospital due to a hemorrhagic stool. The patient presented transient hemorrhagic shock and contrast-enhanced CT revealed a hyper-vascularized tumor in the small bowel. India ink tattooing for the responsible lesion with double-balloon endoscopy was performed. The tattooed lesion was easily confirmed during the subsequent laparoscopic observation and segmental resection was done. Pathological examination showed arteriovenous malformation of the small bowel.

Discussion: Prior to laparoscopic resection, the localization of the responsible area might be a significant consideration when the lesion is invisible. Endoscopic marking with DBE enables intraluminal detection and laparoscopic observation from the serosal side.

Conclusion: Preoperative marking with the use of double-balloon endoscopy followed by laparoscopic resection might be an optimal option for the treatment of massive small intestinal bleeding.
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http://dx.doi.org/10.1016/j.ijscr.2019.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526289PMC
May 2019

[Two Cases of Colorectal Liver Metastasis with Localized Biliary Dilatation].

Gan To Kagaku Ryoho 2019 Mar;46(3):537-539

Dept. of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center.

We encountered 2 cases of colorectal liver metastasis with biliarydilatation mimicking cholangiocarcinoma. Case 1: A 70- year-old male patient, who was diagnosed with colorectal cancer and underwent transverse colectomy3 years prior, was preoperativelydiagnosed with cholangiocarcinoma with biliarydilatation of the medial and lateral segments. He underwent left hemi-hepatectomy. The pathological diagnosis was colorectal liver metastasis with intra-biliarytumor thrombosis. Case 2: A 67-year-old male patient was diagnosed with descending colon cancer and cholangiocarcinoma with biliarydilatation of the medial segment. He underwent left hemi-colectomyand left hemi-hepatectomy. The pathological diagnosis was descending colon cancer and colorectal liver metastasis with biliaryinfiltration. The immunopathological findings showed double positivityfor CK20 and CDX2 antibodies and negativityfor CK7 antibodyin these cancer lesions.
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March 2019

[Surgical Resection of Hepatic Portal Lymph Node Metastasis after Repeated Treatment for Hepatocellular Carcinoma Recurrence].

Gan To Kagaku Ryoho 2018 Dec;45(13):2003-2005

Dept. of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center.

We encountered a case of hepatic portal lymph node metastasis after repeated treatment for hepatocellular carcinoma (HCC)recurrence. A 73-year-old male patient underwent partial gastrectomy following rupture of a gastrointestinal stromal tumor 8 years ago. A 70mm tumor was simultaneously revealed in the posterior segment of the liver, and imatinib treatment was initiated based on the diagnosis of a metastatic liver tumor. Due to the absence of an increasing tendency in the tumor, extended posterior segmentectomy was performed, and the pathological diagnosis was moderately differentiated HCC. During observation, transcatheter arterial chemoembolization(TACE)plus radiofrequency ablation(RFA)therapy was performed twice, and partial resection of the liver was performed once again for HCC recurrence. Recently, PIVKA-Ⅱ showed a high value of 1,720mAU/mL, and follow-up computed tomography showed HCC recurrence in S4/8 and hepatic portal lymph node metastasis. TACE was administered for recurrent lesions in S4/8, and surgical resection of the hepatic portal lymph node was performed together. The pathological diagnosis revealed extensive liver tissue necrosis and moderately-topoorly differentiated HCC in the excised lymph nodes. Lymph node metastasis of HCC is rare, and in this case, a change in lymph flow caused by repeated treatment for HCC recurrence was considered a factor influencing the course.
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December 2018

[A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

Gan To Kagaku Ryoho 2018 Dec;45(13):2150-2152

Dept. of Surgery, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center.

A 71-year-old man was diagnosed as having Type 2 gastric cancer(tub2, HER2-negative). Abdominal computed tomography( CT)revealed bulky metastatic lymph nodes around the stomach and para-aorta(No. 16a2, b1). Our clinical diagnosis was cT4a(SE)N+M1(PAN), cStage Ⅳb, and SOX therapy was immediately administered. After 3 courses of chemotherapy, the treatment effect was PR, and after 6 courses, the patient was diagnosed with ycT2(MP)N0M0, ycStageⅠB. No Grade 2 or higher adverse events were observed during chemotherapy. At this stage, we determined that radical resection was feasible; thus, distal gastrectomy and D3 dissection(para-aortic lymph node dissection)were performed. No cancer cells were found in the primary lesion on histopathology. The histological response of the primary lesion was Grade 3, and the lymph node was Grade 2b. On follow-up observation, the patient is alive without tumor recurrence at 1 year postoperatively.
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December 2018

Comparison Between Stereotactic Radiotherapy and Sublobar Resection for Non-Small Cell Lung Cancer.

Ann Thorac Surg 2019 05 17;107(5):1544-1550. Epub 2018 Nov 17.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Background: The aim of this study was to compare outcomes of primary treatment with stereotactic body radiation therapy (SBRT) versus sublobar resection (SLR) for clinical stage I non-small cell lung cancer (NSCLC) in patients with medical comorbidities.

Methods: Consecutive patients who underwent SBRT (n = 106) or SLR (100 wedge resection, 41 segmentectomy) because of medical comorbidities associated with stage I NSCLC were enrolled. Lesions located in the outer third of the lung field on computed tomography were defined as external, and others were defined as internal. A propensity score-matched analysis was also performed that compared SBRT and SLR results. Charts were reviewed to determine local tumor recurrence, disease-specific survival (DSS), and overall survival (OS).

Results: A propensity score-matched analysis, recurrence-free survival (RFS) became significant in favor of surgery (p = 0.036). For large nodules of greater than 2.0 cm in diameter, RFS was significantly better in the surgery group (p = 0.042). No significant differences in OS, DSS, or RFS were observed with small nodules of less than 2.0 cm in diameter. In the external group, a higher recurrence rate was seen for SBRT group. For internal group, there was no statistical difference between each treatment. Local recurrence rate was higher in the SBRT group (p = 0.0082) in the external group.

Conclusions: In a matched comparison of stage I NSCLC in patients with medical comorbidities, RFS was in favor of surgery comparing SBRT, but there were no significant differences in OS or DSS. The tumor size and tumor location should be considered before deciding whether to perform SBRT or surgery.
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http://dx.doi.org/10.1016/j.athoracsur.2018.10.015DOI Listing
May 2019

[Misdirection of an Indwelling Urethral Catheter into the Ureter in a Female Patient with Neurogenic Bladder : A Case Report].

Hinyokika Kiyo 2018 Mar;64(3):123-126

The Department of Urology, Kobe City Nishi-Kobe Medical Center.

We report a case of misdirection of an indwelling urethral catheter into the ureter. An 86-year-old women with neurogenic bladder had been undergoing chronic indwelling urethral catheter exchange for 1 year. She was referred to our hospital owing to lower abdominal pain and gross hematuria. A computed tomographic scan showed an indwelling urethral catheter in the right ureter. Retrograde ureterography showed that the ureter had no leakage and the catheter was removed under fluoroscopic guidance. Urethral catheterization is a common procedure. We reviewed 23 cases of an indwelling urethral catheter entering the ureter and we consider that this misdirection occurs particularly among female patients with neurogenic bladder.
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http://dx.doi.org/10.14989/ActaUrolJap_64_3_123DOI Listing
March 2018

Aneurysm of the inferior vena cava with thrombosis.

Clin Case Rep 2018 02 13;6(2):402-406. Epub 2018 Jan 13.

Department of Surgery National Hospital Organization Kure Medical Center Chugoku Cancer Center Kure Japan.

Inferior vena cava (IVC) aneurysms are extremely rare. Patients can be asymptomatic, have thrombosis, rupture, or pulmonary embolism. Thrombosis of the IVC aneurysm may mimic a retroperitoneal tumor. Surgical treatment of abdominal venous aneurysms with thrombosis is warranted and is necessary for the management of intraoperative bleeding and thrombosis.
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http://dx.doi.org/10.1002/ccr3.1321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799648PMC
February 2018

Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer.

Oncol Lett 2018 Jan 2;15(1):400-406. Epub 2017 Nov 2.

Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima 737-0023, Japan.

The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1-3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1-19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20-21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases.
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http://dx.doi.org/10.3892/ol.2017.7339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769419PMC
January 2018

[A Resectable Case of TS-1 Therapy Useful in Distinguishing Primary Lung Cancer from Lung Metastases of Pancreatic Cancer].

Gan To Kagaku Ryoho 2018 Jan;45(1):88-90

Dept. of Surgery, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center.

We report a case of pneumonectomy followed by radical pancreatectomy after oral administration of TS-1 for pancreatic cancer with complications ofa lung tumor. The patient was a 66-year-old woman. A pancreatic tail tumor and 2 lung nodules were detected on CT scans, and were diagnosed as pancreatic cancer and metastatic lung cancer. During a total of1 1 courses ofTS -1 therapy, the pancreatic tumor tended to contract, but both pulmonary nodules remained unchanged. Due to differences in treatment effect, double cancers of the lung and pancreas were suspected, rather than metastatic lung cancers. We performed a VATS partial resection of the left lower lobe for diagnostic therapy. The pathological diagnosis revealed an inflammatory myofibroblastic tumor and a primary lung cancer. We diagnosed that a radical pancreatectomy was possible and performed distal pancreatectomy. Pathological diagnosis confirmed an invasive pancreatic ductal carcinoma. Oral administration ofTS -1 was performed as adjuvant chemotherapy after surgery. Liver metastasis was observed 10 months after pancreatectomy, and GEM therapy was initiated. Peritoneal dissemination was observed at 2 years following pancreatectomy, and the patient died at 2 years and 9 months. TS-1 therapy for synchronous lung tumors and pancreatic cancer with careful observation allowed for a definitive radical resection. This method was an effective treatment for lung nodules with pancreatic cancer.
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January 2018

[An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors].

Hinyokika Kiyo 2017 Sep;63(9):363-369

The Department of Urology, Nishi-Kobe Medical Center.

Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women.
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http://dx.doi.org/10.14989/ActaUrolJap_63_9_363DOI Listing
September 2017

[A Case of Primary Sigmoid Colon Lymphoma Presenting with Sigmoidovesical Fistula in a Patient with a Long History of Ulcerative Colitis].

Hinyokika Kiyo 2017 Aug;63(8):319-322

The Department of Urology, Nishi-Kobe Medical Center.

A 73-year-old male patient with a 16-year history of ulcerative colitis presented to our hospital with a history of pneumaturia and fever. Cystoscopy and a computed tomography scan showed sigmoidovesical fistula. Colonoscopy showed a necrotic tumor along with sigmoidovesical fistula. A biopsy was not sufficient to make a definitive diagnosis of the tumor. Total colectomy with ileostomy and partial cystectomy were performed. A pathological examination showed diffuse large B-cell lymphoma of the sigmoid colon. On postoperative day 35, delayed dehiscence of the bladder wall was detected and a biopsy of the bladder wall showed lymphoma. Standard systemic chemotherapy (R-THP-COP) was administered and the defect of the bladder was closed. Three years and 2 months postoperatively, the patient has no local recurrence or distant metastasis.
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http://dx.doi.org/10.14989/ActaUrolJap_63_8_319DOI Listing
August 2017