Publications by authors named "Hiroshi Shiratori"

8 Publications

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Impact of Inferior Mesenteric Artery Occlusion on the Calibre of Collateral Arteries of the Colon.

Anticancer Res 2021 Oct;41(10):5189-5193

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: The inferior mesenteric arteries (IMA) are occluded in some colorectal cancer patients. This study evaluated the impact of IMA occlusion on the calibre of collateral arteries.

Patients And Methods: As an IMA obstruction model, 20 patients who underwent abdominal aortic aneurysm surgery, with ligated, excluded, or embolised IMA, were enrolled. Changes in the calibre of the left colic arteries (LCAs) and marginal arteries after surgeries were evaluated.

Results: The cross-sectional area of the LCA significantly increased after surgery (4.34 mm vs. 6.34 mm, p=0.0009) and that of the marginal artery did not change significantly (2.69 mm vs. 3.01 mm, p=0.33).

Conclusion: The calibre of the LCA increased after IMA occlusion. The descending branch of the LCA should be confirmed preoperatively to preserve blood flow during a low tie procedure.
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http://dx.doi.org/10.21873/anticanres.15337DOI Listing
October 2021

Optimal Size Criteria for Lateral Lymph Node Dissection After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Dis Colon Rectum 2021 03;64(3):274-283

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Although chemoradiotherapy followed by radical surgery without lateral lymph node dissection is the current standard treatment in patients with rectal cancer, recent studies have demonstrated the benefits of adding lateral lymph node dissection to total mesorectal excision in patients with suspected lateral lymph node metastasis. However, the optimal indication for lateral lymph node dissection after chemoradiotherapy has not been determined.

Objective: This study aimed to establish the optimal indication for lateral lymph node dissection after chemoradiotherapy in patients with rectal cancer.

Design: This is a retrospective study.

Settings: This study was conducted at a single referral hospital.

Patients: A total of 279 patients with rectal cancer who underwent chemoradiotherapy followed by radical surgery between 2007 and 2018 were retrospectively enrolled.

Main Outcome Measures: The largest lateral lymph nodes on CT were retrospectively assessed and compared with the pathologic results of dissected lateral lymph nodes and recurrences in lateral lymph node areas.

Results: The incidence of lateral lymph node metastasis after chemoradiotherapy was estimated to be 9.3%. Although patients with lateral lymph node metastasis frequently developed distant recurrence, 40.4% survived for >5 years without recurrence. An analysis of the lateral lymph node sizes showed that lateral lymph node size ≥8 mm before chemoradiotherapy was the optimal criterion for lateral lymph node dissection, with a sensitivity and specificity of 92.3% and 78.7%. Using this criterion, 72.0% of the patients could be spared lateral lymph node dissection.

Limitations: Because of the retrospective nature of the present study, the selection of patients who underwent lateral lymph node dissection was biased.

Conclusions: The optimal indication for lateral lymph node dissection was lateral lymph node size ≥8 mm before chemoradiotherapy. Cancer could be eradicated in >30% of patients with lateral lymph node metastasis by dissecting metastatic lateral lymph nodes. See Video Abstract at http://links.lww.com/DCR/B428.

Criterios De Tamao Ptimo Para La Diseccin De Ganglios Linfticos Laterales Despus De La Quimiorradioterapia Neoadyuvante Para El Cncer De Recto: ANTECEDENTES:Aunque la quimiorradioterapia seguida por cirugía radical sin disección de ganglios linfáticos laterales es el tratamiento estándar actual en pacientes con cáncer de recto, estudios recientes han demostrado beneficios de agregar disección de ganglios linfáticos laterales a la escisión mesorrectal total en pacientes con sospecha de metástasis de ganglios linfáticos laterales. Sin embargo, no se ha determinado la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia.OBJETIVO:Este estudio tuvo como objetivo establecer la indicación óptima para la disección de los ganglios linfáticos laterales después de la quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un solo hospital de referencia.PACIENTES:Se inscribieron retrospectivamente un total de 279 pacientes con cáncer de recto que se sometieron a quimiorradioterapia seguida por cirugía radical entre 2007 y 2018.PRINCIPALES MEDIDAS DE VALORACION:Los ganglios linfáticos laterales más grandes en la tomografía computarizada se evaluaron retrospectivamente y se compararon con los resultados patológicos de los ganglios linfáticos laterales disecados y recidivas en las áreas de los ganglios linfáticos laterales.RESULTADOS:Se estimó que la incidencia de metástasis en los ganglios linfáticos laterales después de la quimiorradioterapia fue del 9,3%. Aunque los pacientes con metástasis en los ganglios linfáticos laterales con frecuencia desarrollaron recurrencia a distancia, el 40,4% sobrevivió durante más de 5 años sin recurrencia. Un análisis de los tamaños de los ganglios linfáticos laterales mostró que la mayor dimensión de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia eran el criterio óptimo para la disección de los ganglios linfáticos laterales, con una sensibilidad y especificidad del 92,3% y 78,7%, respectivamente. Utilizando este criterio, el 72,0% de los pacientes podría evitarse la disección de los ganglios linfáticos laterales.LIMITACIONES:Debido a la naturaleza retrospectiva del presente estudio, la selección de pacientes que fueron sometidos a disección de ganglios linfáticos laterales fue sesgada.CONCLUSIÓN:La indicación óptima para la disección de los ganglios linfáticos laterales fue la dimensión mayor de los ganglios linfáticos laterales ≥ 8 mm antes de la quimiorradioterapia. El cáncer se podría erradicar en más del 30% de los pacientes con metástasis en los ganglios linfáticos laterales disecando los ganglios linfáticos laterales metastásicos. Consulte Video Resumen en http://links.lww.com/DCR/B428.
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http://dx.doi.org/10.1097/DCR.0000000000001866DOI Listing
March 2021

Epithelial-mesenchymal transition and metastatic ability of CD133 colorectal cancer stem-like cells under hypoxia.

Oncol Lett 2021 Jan 9;21(1):19. Epub 2020 Nov 9.

Department of Surgical Oncology, The University of Tokyo, Tokyo 113-8655, Japan.

Although CD133 is a representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia remains unclear. Therefore, the present study aimed to investigate the associations between CD133, the epithelial-mesenchymal transition and distant metastasis in colorectal cancer. CD133 and CD133 cells were isolated from a single colorectal cancer cell line LoVo, and their adhesive and migratory properties were compared under hypoxic conditions. Immunostaining analysis was performed to determine CD133 expression in clinical samples of primary tumors, as well as liver and peritoneal metastases. Under hypoxia, the expression levels of hypoxia-inducible factor (HIF)-1α and the epithelial-mesenchymal transition markers N-cadherin and vimentin were significantly higher in the CD133 compared with those in the CD133 cells. Furthermore, the migratory ability of the CD133 cells was higher compared with that of the CD133 cells under hypoxia. By contrast, the expression levels of β1 integrin were significantly lower in the CD133 cells under hypoxia compared with those in the CD133 cells. Immunohistochemical analysis of clinical samples revealed that the levels of CD133 expression in metastatic tissues from the liver were significantly higher compared with those in the corresponding primary tumors, whereas CD133 expression levels in peritoneal metastatic tissues were significantly lower compared with those in the corresponding primary tumors. In conclusion, compared with the CD133 cells, the CD133 colorectal cancer cells exhibited enhanced levels of HIF-1α expression and tumor cell migration during hypoxia. This was associated with an increased ability of epithelial-mesenchymal transition, possibly leading to the acquisition of an increased hematogenous metastatic potential and eventually resulting in liver metastasis. High β1 integrin expression levels in the CD133 cells under hypoxia may serve a key role in cell adhesion to the peritoneum, resulting in peritoneal metastasis.
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http://dx.doi.org/10.3892/ol.2020.12280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681219PMC
January 2021

Risk factors and therapeutic significance of inguinal lymph node metastasis in advanced lower rectal cancer.

Int J Colorectal Dis 2020 Apr 3;35(4):655-664. Epub 2020 Feb 3.

Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: This study aimed to clarify predictors and therapeutic significance of inguinal lymph node metastasis (ILNM) in patients with rectal cancer.

Methods: Patients with rectal adenocarcinoma invading the anal canal who underwent curative surgery between 2003 and 2019 were retrospectively reviewed. Synchronous and metachronous lymph node (LN) metastasis were collectively defined as final nodal metastasis (f-LNM). Factors associated with f-LNM were analyzed. Moreover, the "modified therapeutic value index," defined by multiplication of the frequency of f-LNM by the 5-year overall survival rate for patients who received treatment for f-LNM, was calculated for each LN area.

Results: A total of 145 patients were enrolled (16 patients with f-ILNM). To predict f-ILNM, the cutoff of the inguinal lymph node (ILN) diameter of 8.5 mm gave an area under the curve of 0.889. Dentate line involvement (odds ratio 33.4) and ILN larger than the cutoff of 8 mm (odds ratio 11.9) were independently associated with f-ILNM. The modified therapeutic value indices of the inguinal, lateral pelvic, and mesorectal LNs in the entire population were 6.1, 8.2, and 20.3 points, respectively. In patients with dentate line invasion by cancer, the index of the ILN increased to 11.7 points. In patients with an ILN > 8 mm, the index further increased to 21.1 points.

Conclusion: Dentate line involvement and ILN > 8 mm predicted the development of ILNM in patients with rectal cancer invading the anal canal. Treatment of the ILN should be considered for patients with the above predictors given the significant therapeutic outcomes.
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http://dx.doi.org/10.1007/s00384-020-03520-2DOI Listing
April 2020

Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.

Cancer Sci 2020 Apr 22;111(4):1291-1302. Epub 2020 Feb 22.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Postoperative distant metastasis dramatically affects rectal cancer patients who have undergone neoadjuvant chemoradiotherapy (NACRT). Here, we clarified the association between NACRT-mediated mammalian target of rapamycin (mTOR) signaling pathway activation and rectal cancer metastatic potential. We performed immunohistochemistry for phosphorylated mTOR (p-mTOR) and phosphorylated S6 (p-S6) on surgical specimen blocks from 98 rectal cancer patients after NACRT (cohort 1) and 80 colorectal cancer patients without NACRT (cohort 2). In addition, we investigated the association between mTOR pathway activity, affected by irradiation, and the migration ability of colorectal cancer cells in vitro. Based on the results of the clinical study, p-mTOR was significantly overexpressed in cohort 1 (with NACRT) as compared to levels in cohort 2 (without NACRT) (P < .001). High p-mTOR and p-S6 levels correlated with the development of distant metastasis only in cohort 1. Specifically, high p-S6 expression (HR 4.51, P = .002) and high pathological T-stage (HR 3.73, P = .020) after NACRT were independent predictors of the development of distant metastasis. In vitro, p-S6 levels and migration ability increased after irradiation in SW480 cells (TP53 mutation-type) but decreased in LoVo cells (TP53 wild-type), suggesting that irradiation modulates mTOR signaling and migration through cell type-dependent mechanisms. We next assessed the expression level of p53 by immunostaining in cohort 1 and demonstrated that p-S6 was overexpressed in samples with high p53 expression as compared to levels in samples with low p53 expression (P = .008). In conclusion, p-S6 levels after NACRT correlate with postoperative distant metastasis in rectal cancer patients, suggesting that chemoradiotherapy might modulate the mTOR signaling pathway, promoting metastasis.
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http://dx.doi.org/10.1111/cas.14332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156826PMC
April 2020

The combination of temsirolimus and chloroquine increases radiosensitivity in colorectal cancer cells.

Oncol Rep 2019 Jul 23;42(1):377-385. Epub 2019 Apr 23.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, The University of Tokyo, Tokyo 113‑8655, Japan.

The PI3K/AKT/mTOR pathway and autophagy are known to play important roles in cancer radioresistance. The aim of the present study was to investigate whether the combination of temsirolimus (TEM), an mTOR inhibitor, and chloroquine (CQ), an autophagy inhibitor, can increase radiosensitivity in colorectal cancer (CRC) cells. The efficacies of TEM and/or CQ as radiosensitizers were examined using clonogenic assays in CRC cell lines SW480 and HT‑29. The expression levels of the phosphorylated isoforms of S6 and 4E‑BP1, downstream proteins of mTOR, as well as the expression levels of p62 and LC3, autophagy‑related proteins, were assessed by western blot analysis. The formation of acidic organelles was detected in acridine orange‑stained cells. Apoptosis and caspase activity were assessed using flow cytometry. The results revealed that ionizing radiation (IR) activated the downstream proteins of mTOR and induced autophagy. In the clonogenic assays, neither TEM nor CQ influenced the efficacy of IR, whereas their combination significantly increased the dose‑dependent efficacy of IR. TEM inhibited phosphorylation of the downstream proteins of mTOR and induced autophagy. CQ inhibited autophagy in the late phase and did not influence the downstream proteins of mTOR. TEM and CQ inhibited both the phosphorylation of downstream proteins of mTOR and autophagy. Cell death analysis revealed that the combination of TEM and CQ strongly induced apoptosis in cells exposed to IR. In conclusion, the combination of TEM and CQ increased radiosensitivity in CRC cells through co‑inhibition of mTOR and autophagy.
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http://dx.doi.org/10.3892/or.2019.7134DOI Listing
July 2019

Correlations between the Recurrence Patterns and Sizes of Lateral Pelvic Lymph Nodes before and after Chemoradiotherapy in Patients with Lower Rectal Cancer.

Oncology 2019 13;96(1):33-43. Epub 2018 Sep 13.

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Objective: Factors that predict rectal cancer metastasis to the lungs remain undefined. We investigated whether the lateral pelvic lymph node (LPN) sizes before and after chemoradiotherapy (CRT) correlate with lung metastasis after surgery for lower rectal cancer.

Methods: Two hundred and forty patients with lower rectal cancer who received preoperative CRT and curative surgery between 2003 and 2017 were examined. Computed tomography-measured LPN sizes before and after CRT were retrospectively determined by 1 colorectal surgeon who was blinded to the patients' clinical and pathological outcomes.

Results: The 5-year cumulative lung metastasis rates were 15.2%. The mean LPN sizes in patients who developed lung metastasis were larger than those in patients who did not (pre-CRT: 8.7 vs. 6.3 mm, p = 0.003; post-CRT: 6.8 vs. 4.5 mm, p = 0.001). The cumulative lung metastasis rate in patients with large LPNs was higher than in those with small LPNs both before and after CRT. On multivariate analysis, lung metastasis was independently correlated with the LPN size only after CRT (hazard ratio [HR]: 5.58), together with the ypT stage (HR: 2.96) and the tumor location (HR: 0.38).

Conclusions: LPN size after CRT is strongly predictive of postoperative lung metastasis in patients with lower rectal cancer.
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http://dx.doi.org/10.1159/000492493DOI Listing
December 2018

Perforation of jejunal diverticulum with ectopic pancreas.

Clin J Gastroenterol 2017 Apr 19;10(2):137-141. Epub 2017 Jan 19.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, 113-8655, Japan.

Perforation of jejunal diverticulum is a rare complication. Here, we report a case of jejunal diverticulum penetration with surrounding ectopic pancreas. An 83-year-old female patient was admitted to our department with acute onset of severe abdominal pain lasting for half a day. Abdominal computed tomography showed outpouching of the small intestine that contained air/fluid, with multiple surrounding air bubbles in the mesentery of the small intestine. She was diagnosed with penetration of the small intestine, and an emergency laparotomy was indicated. The penetrated jejunal diverticulum was identified ~20-cm distal to the ligament of Treitz. Partial resection of the jejunum was performed, and her postoperative course was uneventful. The pathological findings confirmed diverticulum penetration into the mesentery and severe inflammation at the site, with surrounding ectopic pancreas. Furthermore, the pancreatic ducts were opened through the penetrated diverticulum. This rare case shows that the ectopic pancreas might have caused penetration of jejunal diverticulum owing to the pancreatic duct opening through the diverticulum.
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http://dx.doi.org/10.1007/s12328-017-0712-9DOI Listing
April 2017
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