Publications by authors named "Mitsuaki Ishida"

230 Publications

Immunohistochemical comparison of three programmed death-ligand 1 (PD-L1) assays in triple-negative breast cancer.

PLoS One 2021 24;16(9):e0257860. Epub 2021 Sep 24.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. A recent study demonstrated the efficacy of anti-PD-L1 (anti-programmed death ligand-1) immunotherapy in patients with TNBC. However, the identification of TNBC patients who may benefit from immunotherapy is a critical issue. Several assays have been used to evaluate PD-L1 expression, and a few studies comparing PD-L1 expression using various primary antibodies in TNBC tissues have been reported. However, the expression profiles of the PD-L1 using the 73-10 assay have not yet been analyzed in TNBC tissues.

Methods: We analyzed the PD-L1 immunohistochemical profiles of 62 women with TNBC using the 73-10, SP142 (companion diagnostic for atezolizumab), and E1L3N assays. PD-L1 expression on immune cells (ICs) and tumor cells (TCs) was also evaluated, and PD-L1 positivity was defined as a PD-L1-expressing ICs or TCs ≥ 1%.

Results: The expression rates of PD-L1 were 79.0%, 67.7%, and 46.8% on ICs, and 17.7%, 6.5%, and 12.9% on TCs using the 73-10, SP142, and E1L3N assays, respectively. The concordance rates between the 73-10 and SP142 assays were 85.5% (on ICs) and 88.7% (on TCs), respectively, and substantial agreement on ICs (coefficient 0.634) and moderate agreement (coefficient 0.485) on TCs were noted. Sample age and tumor diameter did not influence the ratio of PD-L1 expression among the assays.

Conclusions: The positive rate on ICs and TCs of the 73-10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73-10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257860PLOS
September 2021

Validation of the triple-checked criteria for drain management after pancreatectomy.

J Hepatobiliary Pancreat Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Surgery, Kansai Medical University, Hirakata, Japan.

Background: Drain management is important for the detection and treatment of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously established the triple-checked criteria for drain removal: drain fluid amylase (DFA) <5000 U/L on postoperative day (POD) 1 and DFA <3000 U/L on POD 3, or C-reactive protein <15 mg/dL on POD 3. This study aimed to validate the efficacy of the triple-checked criteria.

Methods: In this study, 681 patients who underwent pancreatectomy were included. Drains were removed according to our previous criteria (sequentially checked criteria: DFA <5000 U/L on POD 1 and DFA <3000 U/L on POD 3) from 2012 to 2016 (control group) and the triple-checked criteria from 2017 to 2019 (intervention group).

Results: The control group included 406 patients, and the intervention group included 275 patients. Significantly more patients (n = 237, 86.2%) met the triple-checked criteria in the intervention group, relative to the sequentially checked criteria for early drain removal policy (n = 309, 76.1%; P = .001). Sensitivity, accuracy, and negative predictive value were significantly higher in the intervention group than in the control group (P < .001). The incidence of CR-POPF was not significantly different (11.1% vs 13.8%, P = .285).

Conclusions: The triple-checked criteria contributed to effective drain removal after pancreatectomy without increasing CR-POPF.
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http://dx.doi.org/10.1002/jhbp.1030DOI Listing
July 2021

A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.

J Hepatobiliary Pancreat Sci 2021 Jul 27. Epub 2021 Jul 27.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Background: We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC.

Methods: Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020.

Results: Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P < .0001) and "high-risk markers" (OR 2.07, P = .011) as independent predictors of OAM. A scoring system consisting of body/tail (yes: 1, no: 0) and "high-risk markers" (yes: 1, no: 0) was constructed. In the validation cohort, when staging laparoscopy (SL) was performed for patients with scores 1/2, the eligibility for SL, sensitivity, and negative predictive value of OAM were 55%, 91%, and 96%, respectively.

Conclusions: Tumor location of body/tail and "high-risk markers" were independent predictors of OAM, composing our simple and reproducible risk scoring system.
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http://dx.doi.org/10.1002/jhbp.1026DOI Listing
July 2021

[Diagnosis of Serous Adenocarcinoma following Pneumatosis Intestinalis Development during Bevacizumab Therapy for Cancer of Unknown Primary-A Case Report].

Gan To Kagaku Ryoho 2021 Jul;48(7):979-982

Dept. of Gastrointestinal Surgery, Kansai Medical University Hospital.

A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.
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July 2021

Right epipericardial fat necrosis after thymectomy.

Ann Thorac Surg 2021 Jun 29. Epub 2021 Jun 29.

Kansai Medical University, Department of Thoracic Surgery, Osaka, Japan, 2-3-1 Shinmachi Hirakata-shi, Osaka 573-1191, Japan.

A male patient in his sixties underwent median sternotomy and thymectomy for thymoma (WHO classification type B1+B3, Masaoka classification stage II). A 10-month follow-up postoperative computed tomography showed a 22-mm nodule in the anterior mediastinal lipid tissue just above the right diaphragm. The patient was followed for 8 years and the nodule's capsule eventually became calcified. Considering the possibility of postoperative recurrence of thymoma, we excised the nodule. The pathological diagnosis was epipericardial fat necrosis. In some cases, fat necrosis is difficult to distinguish from malignancy by imaging only; surgical resection has diagnostic significance and should be considered.
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http://dx.doi.org/10.1016/j.athoracsur.2021.06.013DOI Listing
June 2021

Immunohistochemical analysis of CD155 expression in triple-negative breast cancer patients.

PLoS One 2021 11;16(6):e0253176. Epub 2021 Jun 11.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Introduction: CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail.

Methods: Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73-10 assays), was also examined.

Results: CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73-10 assay did not show a correlation (p = 0.115). Using the 73-10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively).

Conclusions: CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253176PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195407PMC
June 2021

Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Surg Today 2021 Jun 4. Epub 2021 Jun 4.

Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-City, Osaka, 573-1010, Japan.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.
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http://dx.doi.org/10.1007/s00595-021-02308-3DOI Listing
June 2021

Usefulness and problems of cytological examination by endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal lymphadenopathy: A retrospective single-centre study.

Mol Clin Oncol 2021 Jul 19;15(1):138. Epub 2021 May 19.

Department of Pathology and Clinical Laboratory, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive and useful technique for sampling mediastinal lymph nodes. High sensitivity and specificity of EBUS-TBNA in staging lung cancer have been reported. However, few studies have addressed the results of EBUS-TBNA in the diagnosis of mediastinal lymphadenopathy with or without lung cancer, since various neoplastic and non-neoplastic conditions can involve the mediastinal lymph nodes. The present study analysed the results of the cytological examination of mediastinal lymphadenopathy using EBUS-TBNA in Kansai Medical University Hospital (Hirakata, Japan). A total of 41 consecutive patients with mediastinal lymphadenopathy who underwent EBUS-TBNA between January 2008 and December 2019 in Kansai Medical University Hospital were enrolled. This cohort included 29 males and 12 females. Cytological analyses demonstrated that 16/17 (94.1%) patients with metastatic carcinoma were diagnosed as having carcinoma (malignancy). The sensitivity, specificity and positive predictive value of the cytological examination in cases of carcinoma were 94.1, 100 and 100, respectively. However, only 3/11 (27.3%) patients with sarcoidosis were diagnosed by cytological examination. The present study demonstrated that EBUS-TBNA may be a useful method for detecting metastatic carcinoma in the mediastinal lymph nodes. However, the detection rate of epithelioid granuloma, which is a characteristic feature of sarcoidosis, was low in the present cohort. Hence, an improvement in the sampling technique is necessary.
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http://dx.doi.org/10.3892/mco.2021.2300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145344PMC
July 2021

Clinicopathological characteristics of pancreatic ductal adenocarcinoma with invasive micropapillary carcinoma component with emphasis on the usefulness of PKCζ immunostaining for detection of reverse polarity.

Oncol Lett 2021 Jul 13;22(1):525. Epub 2021 May 13.

Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component. Clinicopathological characteristics were compared between the IMPC and non-IMPC groups. Immunohistochemical staining for PKCζ was performed using an autostainer. In total, 14 cases had an IMPC component (5.8%). The extent of IMPC component ranged from 5 to 20%. There were no significant differences in tumor location, T category, lymph node metastatic status, preoperative carbohydrate antigen 19-9 level, resection status and overall survival between the IMPC and non-IMPC groups. Immunostaining for PKCζ clearly showed reverse polarity of the neoplastic cells of IMPC. Although previous reports have shown that the presence of an IMPC component (>20% of the tumor) indicated poor prognosis, the present study demonstrated that presence of IMPC <20% did not suggest a worse prognosis.
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http://dx.doi.org/10.3892/ol.2021.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138900PMC
July 2021

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors.

BMC Cancer 2021 Apr 27;21(1):470. Epub 2021 Apr 27.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Osaka, Japan.

Background: Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence.

Methods: The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for "mucus extension."

Results: The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019).

Conclusions: During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.
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http://dx.doi.org/10.1186/s12885-021-08231-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080361PMC
April 2021

Utility of an immunocytochemical analysis for pan-Trk in the cytodiagnosis of secretory carcinoma of the salivary gland.

Diagn Cytopathol 2021 Aug 22;49(8):E329-E335. Epub 2021 Apr 22.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6-NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan-tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan-Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine-needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan-Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet-like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi-vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan-Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan-Trk, immunocytochemical analysis for pan-Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features.
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http://dx.doi.org/10.1002/dc.24750DOI Listing
August 2021

Induction of the epithelial-mesenchymal transition in the endometrium by chronic endometritis in infertile patients.

PLoS One 2021 7;16(4):e0249775. Epub 2021 Apr 7.

Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Background: The purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase.

Methods: Endometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed.

Results: The rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition.

Conclusion: The epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249775PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026044PMC
September 2021

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

Pancreatology 2021 Aug 19;21(5):884-891. Epub 2021 Mar 19.

Department of Surgery, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Background: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma.

Methods: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively.

Results: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival.

Conclusion: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.
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http://dx.doi.org/10.1016/j.pan.2021.03.008DOI Listing
August 2021

Prognostic significance of PD-L1-positive cancer-associated fibroblasts in patients with triple-negative breast cancer.

BMC Cancer 2021 Mar 6;21(1):239. Epub 2021 Mar 6.

Department of Surgery, Kansai Medical University, 2-5-1, Shinmachi, Osaka, Hirakata City, Japan.

Background: Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1.

Methods: Immunohistochemical staining (primary antibodies of 73-10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined.

Results: Thirty-four (55.7%) patients were positive for CAF PD-L1 (73-10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73-10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044-0.891; p = 0.035).

Conclusions: CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73-10 assay may be suitable for immunostaining CAF PD-L1.
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http://dx.doi.org/10.1186/s12885-021-07970-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937297PMC
March 2021

Review of the cytological features of olfactory neuroblastoma: A retrospective single-center study.

Diagn Cytopathol 2021 Aug 25;49(8):E301-E306. Epub 2021 Feb 25.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor. Due to the rarity, there are scarce reports describing the cytological features of ONB. Thus, we aimed to analyze these cytological features and discuss their differences depending on the histological grading of ONB. Patients with a histopathological diagnosis of ONB who underwent fine-needle aspiration cytology were enrolled in the study. The cytological features, including arrangement and shape of neoplastic cells, nuclear features, and presence of rosettes, were analyzed. Eight patients with ONB were enrolled; cytological specimens of seven patients were obtained from metastatic lesions and that of one patient were obtained from the nasal cavity tumor. The cytological specimens demonstrated variable-sized clusters of neoplastic cells and single cells. Two-cell pattern, composed of large-sized viable neoplastic cells and small-sized apoptotic cells, was noted in 3 of 4 high-grade ONBs but in none of 4 low-grade ONBs. This reflects that the presence of the two-cell pattern may represent higher proliferation in neoplastic cells. The neoplastic cells had scant cytoplasm and round to oval nuclei containing fine to granular chromatin without conspicuous nucleoli. Rosettes and paranuclear blue bodies were observed in one patient. Most cytological specimens of ONB were obtained from metastatic lesions, especially from the cervical lymph node. Thus, ONB should be differentiated from malignant lymphoma and small cell neuroendocrine carcinoma. Recognition of these cytological features of ONB while considering patient history can aid in correctly diagnosing ONBs. Moreover, the presence of two-cell pattern might reflect high-grade histology of ONB.
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http://dx.doi.org/10.1002/dc.24728DOI Listing
August 2021

Presence of myxoid stromal change and fibrotic focus in pathological examination are prognostic factors of triple-negative breast cancer: Results from a retrospective single-center study.

PLoS One 2021 11;16(2):e0245725. Epub 2021 Feb 11.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Background: Stromal reaction is an important prognostic factor in several cancers, and the presence of myxoid change was assessed as a poor prognostic factor in colorectal cancer. However, the prognostic significance of myxoid change in triple-negative breast cancer (TNBC) remains unknown. This study aimed to determine the prognostic significance of myxoid change and fibrotic focus (FF), which is a fibrotic area within the tumor and considered a poor prognostic indicator in patients with TNBC.

Methods: We enrolled 62 patients with TNBC and reviewed the surgically resected specimens to evaluate myxoid change and FF in the tumor using previously outlined criteria. We evaluated tumor-infiltrating lymphocytes (TILs) using hematoxylin and eosin slides. Overall survival (OS) and relapse-free survival (RFS) were compared based on the presence of myxoid change and/or FF, and the risk factors for RFS were analyzed.

Results: Myxoid change and FF were observed in 25.8% and 33.9% of specimens, respectively. Based on stromal lymphocyte infiltration, 19 patients (30.6%) had high TILs, while the remaining 43 patients (69.4%) had low/intermediate TILs. Presence of myxoid change was significantly correlated with poor OS and RFS (p = 0.040 and 0.031, respectively). FF was also significantly correlated with poor OS and RFS (p = 0.012 and 0.028, respectively). The combination of myxoid change and FF was an independent and poor prognostic factor according to the multivariate analysis (HR 11.61; 95% CI 1.027-131.2; p = 0.048). Presence of myxoid change and FF were significantly associated with low/intermediate TILs in the stroma (p = 0.013).

Conclusions: Histopathological assessment of myxoid change and FF in TNBC may be a useful, practical, and easily assessable method for predicting prognosis in patients with TNBC, which should be confirmed in larger prospective studies. Diagnostic criteria for the establishment of myxoid change and FF in TNBC must be established, and their underlying molecular events must be clarified.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245725PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877644PMC
July 2021

p62 is a useful predictive marker for tumour regression after chemoradiation therapy in patients with advanced rectal cancer: an immunohistochemical study.

Colorectal Dis 2021 May 9;23(5):1083-1090. Epub 2021 Jan 9.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Aim: This study aimed to evaluate the relationship between p62 expression status and tumour regression grade in advanced rectal cancer.

Methods: We enrolled 47 consecutive patients with advanced rectal cancer who underwent chemoradiation therapy (CRT) before surgery. p62 expression in the biopsy specimens was immunohistochemically evaluated, and p62 expression score (staining intensity × positive tumour cells, %) was calculated (range 0-300). The relationship between p62 expression score and CRT effect was analysed.

Results: The staining intensity was +2 and +3 in 29 and 18 patients, respectively. The median proportion of positive neoplastic cells was 87.8%, and that of the p62 expression score was 200. Stronger staining intensity and a higher proportion of p62-positive neoplastic cells were significantly associated with CRT non-effectiveness (P = 0.0002 and P = 0.0116, respectively), and a higher p62 expression score was significantly associated with CRT non-effectiveness (P < 0.0001). The optimal cut-off value for predicting the CRT effect was 240.

Conclusions: A higher p62 expression score was significantly associated with less CRT effectiveness in patients with advanced rectal cancer. Analysis of p62 expression score using biopsy specimens is a useful and easily assessable prediction marker for CRT effect and might help select patients who can undergo a 'watch-and-wait' strategy after CRT.
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http://dx.doi.org/10.1111/codi.15486DOI Listing
May 2021

[Pulmonary Benign Metastasizing Leiomyoma Found as Multiple Bilateral Lung Nodules 11 Years after Hysterectomy;Report of a Case].

Kyobu Geka 2020 Dec;73(13):1128-1131

Department of Thoracic Surgery, Kansai Medical University, Hirakata, Japan.

Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity. We herein report a case of PBML found as multiple bilateral lung nodules 11 years after total hysterectomy. The patient was a 53-year-old woman with past surgical history of abdominal total hysterectomy for a uterine leiomyoma at the age of 42. She was referred to our department for further evaluation of multiple pulmonary nodules detected by a chest radiography. A chest computed tomography revealed multiple bilateral small lung nodules less than 10 mm in diameter. 18-fluorodeoxyglucose (FDG) positron emission tomography showed no significant FDG accumulation to these nodules. The patient finally underwent video assisted thoracoscopic wedge resection of the lower lobe of the right lung for surgical biopsy. The final pathological diagnosis was PBML, based on the comparative evaluation of the surgical specimens from the lung and the uterus. No evidence of enlargement in the remaining pulmonary nodules was noted for 9 months after surgical lung biopsy.
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December 2020

Adipophilin expression is an independent marker for poor prognosis of patients with triple-negative breast cancer: An immunohistochemical study.

PLoS One 2020 17;15(11):e0242563. Epub 2020 Nov 17.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Adipophilin is a lipid droplet-associated protein whose expression can act as a prognostic marker for specific cancers. Using immunohistochemical staining and tissue microarrays, we assayed the expression of adipophilin in 61 patients with triple-negative breast cancer (TNBC) who underwent surgery from January 2006-December 2018. Relapse-free survival (RFS) and its risk factors were analyzed based on adipophilin expression. Fourteen (23.0%) patients expressed adipophilin. As compared to the adipophilin-negative TNBC patients, adipophilin-positive patients exhibited poor RFS (p = 0.032). Among the TNBC patients with a high Ki-67 labeling index, patients negative for adipophilin exhibited better RFS than patients positive for adipophilin (p = 0.032). Moreover, among patients who did not undergo adjuvant chemotherapy, patients negative for adipophilin expression exhibited better RFS than adipophilin-positive patients (p = 0.080). Multivariate analysis showed that adipophilin expression correlated with a high rate of relapse (hazard ratio, 4.89; 95% confidence interval, 1.04-23.0; p = 0.044). Taken together, these results indicate that adipophilin is a novel marker for the poor prognosis of patients with TNBC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242563PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671517PMC
January 2021

Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer.

Cancer Immunol Immunother 2021 Apr 28;70(4):1063-1074. Epub 2020 Oct 28.

Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan.

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non-small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I-IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.
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http://dx.doi.org/10.1007/s00262-020-02755-wDOI Listing
April 2021

Spontaneous infarction of pleomorphic adenoma of the parotid gland: A case report.

Mol Clin Oncol 2020 Dec 17;13(6):68. Epub 2020 Sep 17.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, 573-1010 Osaka, Japan.

Infarction after the fine-needle aspiration (FNA) procedure is a well-recognized phenomenon of salivary gland lesions. Though extremely rare, spontaneous infarction without previous FNA can occur in pleomorphic adenoma (PA). The present report describes a fourth cytological case of spontaneous infarction of PA of the parotid gland using immunocytochemical analysis, to the best of our knowledge, for the first time. A 57-year-old Japanese female presented with persistent swelling of the right neck region. Physical examination revealed a tumour in the right parotid gland, and FNA examination of the tumour was performed following surgical resection. The Papanicolaou smear demonstrated the presence of fully necrotic cell clusters of varying sizes in a necrotic background. Only a few viable cell clusters were observed. These cells were polygonal to spindle-shaped, and exhibited large round to oval nuclei with a conspicuous nucleoli. Although nuclear pleomorphism was noted, the nuclear chromatin was fine. No neoplastic myoepithelial cells were observed. Therefore, it was suspected that these cells were malignant. Immunocytochemical analysis indicated that these atypical cells were positive for p40. Histopathological examination of the resected parotid gland tumour revealed infarcted PA. Our study revealed that the presence of atypical squamous metaplastic cells in a necrotic background was a characteristic cytological feature of infarcted PA, and that these atypical squamous cells can have large nuclei with conspicuous nucleoli and exhibit pleomorphism. Although cytological diagnosis of infarcted PA is difficult, pathologists and cytopathologists must consider the presence of atypical metaplastic squamous cells in benign salivary gland tumours, including infarcted PA.
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http://dx.doi.org/10.3892/mco.2020.2138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520748PMC
December 2020

Signet-ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next-generation sequencing.

J Cutan Pathol 2021 Jan 30;48(1):102-105. Epub 2020 Sep 30.

Department of Pathology and Clinical Laboratory, Kansai Medical University, Osaka, Japan.

Signet-ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85-year-old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet-ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E-cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next-generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.
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http://dx.doi.org/10.1111/cup.13838DOI Listing
January 2021

Intramural bronchogenic cysts of the esophagus and gastroesophageal junction: A case report.

Mol Clin Oncol 2020 Aug 3;13(2):162-168. Epub 2020 Jun 3.

Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.

Bronchogenic cyst is a relatively rare congenital malformation that is often identified in the mediastinum. The occurrence of bronchogenic cysts in the intramural esophagus and gastroesophageal junction is rare. The present report describes three cases of intramural bronchogenic cysts of the esophagus and gastroesophageal junction and reviews the clinicopathological features of these lesions. A 35-year-old Japanese male (Case 1), a 50-year-old Japanese woman (Case 2) and a 34-year-old Japanese man (Case 3) presented with dysphagia, pharyngeal pain and heartburn, respectively. Upper endoscopic examination revealed submucosal tumors in the esophagus (Case 1 and 2) and gastroesophageal junction (Case 3). Subsequent endoscopic examination revealed perforation of the cyst into the surface of the esophageal mucosa (Case 2). Surgical resection was performed in all cases. Histopathological examinations revealed that the submucosal cysts were covered by respiratory-type ciliated epithelium without atypia. Cartilage and bronchial glands were not observed in any of the cases. The present review of the clinicopathological characteristics of bronchogenic cysts of the esophagus and gastroesophageal junction revealed that males and females were equally affected. The median age of the patients was 34.5 years with a wide age distribution. The most common main complaint was dysphagia. A pre-operative diagnosis of bronchogenic cyst is difficult because no specific imaging features are present. As surgical resection is recommended for this lesion, recognition of the clinicopathological features of bronchogenic cysts is important for an accurate pre-operative diagnosis.
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http://dx.doi.org/10.3892/mco.2020.2058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366213PMC
August 2020

Immunohistochemical analysis of SOX2 expression in small-cell neuroendocrine carcinoma of the endometrium.

Mol Clin Oncol 2020 Aug 22;13(2):115-118. Epub 2020 May 22.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.

Small-cell neuroendocrine carcinoma (NEC) of the endometrium is an extremely rare and highly aggressive carcinoma. Sex-determining region Y-box 2 (SOX2) is a master transcription factor regulating the self-renewal, maintenance of stem cell properties and pluripotency of embryonic stem cells, and recent studies revealed that SOX2 plays important roles in cancer growth and progression in several types of carcinomas, including small-cell neuroendocrine carcinoma (NEC) of the lung and oesophagus. Few studies to date have analysed the association between SOX2 and endometrioid carcinoma, whereas the expression of SOX2 in small-cell NEC of the endometrium has not been investigated. The aim of the present study was to analyse the expression status of SOX2, p16 and paired-box gene (PAX) 8, a useful Müllerian marker, in endometrial small-cell NEC. A total of 4 patients with small-cell NEC of the endometrium were enrolled (median age, 70 years). Immunohistochemical studies revealed SOX2 expression in 3 patients and p16 expression in all patients. No patients exhibited positive immunoreactivity for PAX8. SOX2 expression has been reported to be associated with the pathogenesis of small-cell NEC of the oesophagus. Therefore, the results of the present study indicated that SOX2 expression plays an important role in the development of small-cell NEC of the endometrium and the oesophagus. Moreover, expression of p16 and loss of PAX8 do not indicate the origin of small-cell NEC of the endometrium.
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http://dx.doi.org/10.3892/mco.2020.2051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366239PMC
August 2020

A case of IgG4-related anterior mediastinal sclerosing disease coexisting with autoimmune pancreatitis.

Surg Case Rep 2020 Jul 23;6(1):180. Epub 2020 Jul 23.

Department of Thoracic Surgery, Kansai Medical University Hospital, Osaka, Japan.

Background: IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition that predominantly involves exocrine organs. Concerning its thoracic presentation, it often manifests as interstitial lung disease or fibrosing mediastinitis. It is very rare for IgG4-RD to form a well-defined mass in the anterior mediastinum, mimicking an encapsulated thymoma.

Case Presentation: An 82-year-old man with autoimmune pancreatitis under treatment with oral corticosteroids was found to have peripancreatic lymphadenopathy on computed tomography. Subsequent positron emission tomography revealed abnormal uptake (maximal value 3.6) by a thymic mass as well as the peripancreatic lymph nodes. Exacerbation of IgG4-RD was suspected, and we increased the oral steroid dosage. As a result, the peripancreatic lymph nodes, and the anterior mediastinal mass, decreased in size. The thymic mass was suspected to be an encapsulated thymoma because of its lobulated shape, degree of fluorodeoxyglucose accumulation, and response to steroids, and the patient was referred to our department. The serum anti-acetylcholine receptor antibody test was negative. A thoracoscopic tumor resection was performed as diagnostic therapy. Histopathological analysis revealed dense lymphoplasmacytic infiltration with sclerotic stroma within the tumor. Immunohistochemical analysis revealed abundant IgG4-positive plasma cell infiltrates and over 50% IgG4/IgG-positive plasma cells. We did not see either keratin-positive thymocytes or terminal deoxynucleotidyl transferase-positive lymphocytes. Furthermore, deviation in the kappa chain and lambda chain-positive plasma cells was not noted. Accordingly, IgG4-related sclerosing disease was diagnosed.

Conclusions: IgG4-related sclerosing masses in the anterior mediastinum are very rare, and the effect of tumor resection on prognosis remains unclear. IgG4-RD had potentially been categorized as Castleman's disease.
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http://dx.doi.org/10.1186/s40792-020-00939-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378128PMC
July 2020

Preferentially expressed antigen in melanoma as a novel diagnostic marker differentiating thymic squamous cell carcinoma from thymoma.

Sci Rep 2020 07 23;10(1):12286. Epub 2020 Jul 23.

Department of Thoracic Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Thymic squamous cell carcinoma (TSQCC), accounting for 70-80% of thymic carcinoma cases, is distinct from thymoma. However, differential diagnosis for type B3 thymoma is sometimes challenging, even with established markers for TSQCC, including KIT and CD5, which are expressed in ~ 80% of TSQCCs and ~ 3% of thymomas. Novel TSQCC-specific markers would facilitate precise diagnosis and optimal treatment. Herein, we found that preferentially expressed antigen in melanoma (PRAME) may be a novel TSQCC-specific diagnostic marker. We comprehensively profiled 770 immune-related mRNAs in 10 patients with TSQCC and two healthy controls, showing that PRAME and KIT were significantly upregulated in TSQCC (adjusted p values = 0.045 and 0.0011, respectively). We then examined PRAME expression in 17 TSQCCs and 116 thymomas via immunohistochemistry. All 17 (100%) TSQCCs displayed diffuse and strong PRAME expression, whereas eight of 116 (6.8%) thymomas displayed focal and weak expression (p < 0.0001). KIT and CD5 were positive in 17 (100%) and 16 (94.1%) TSQCCs, respectively, whereas one (0.9%) type B3 thymoma showed double positivity for KIT and CD5. The KIT-/CD5-positive type B3 thymoma was negative for PRAME. Thus, combinatorial evaluation of PRAME with KIT and CD5 may facilitate a more precise diagnosis of TSQCC.
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http://dx.doi.org/10.1038/s41598-020-69260-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378236PMC
July 2020

Direct comparison of magnetic resonance imaging and pathological shrinkage patterns of triple-negative breast cancer after neoadjuvant chemotherapy.

World J Surg Oncol 2020 Jul 21;18(1):177. Epub 2020 Jul 21.

Department of Surgery, Kansai Medical University, 2-5-1, Shinmachi, Hirakata City, Osaka Prefecture, Japan.

Background: We aimed to investigate the usefulness of magnetic resonance imaging (MRI) and histopathological shrinkage patterns to formulate a predictive equation for estimating residual tumor size after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) patients.

Methods: We enrolled 34 TNBC patients who underwent MRI before and after NAC. The MRI and histopathological shrinkage patterns were analyzed and classified into five categories-types I and II (concentric shrinkage without or with surrounding lesions, respectively), type III (shrinkage with residual multinodular lesions), type IV (diffuse contrast enhancement in the entire quadrant), and non-visualization. The residual tumor sizes following MRI and histopathological examination were also compared.

Results: The most common MRI and histopathological shrinkage pattern was type I (41.2% and 38.2%, respectively), followed by non-visualization (26.5% and 32.4%, respectively); the concordance rate between MRI and histopathological shrinkage patterns was 41.2%. There was a strong correlation between MRI tumor size and pathological tumor size (r = 0.89). Based on these findings, a predictive equation for pathological tumor size was formulated as follows: pathological tumor size (mm) = 1.1502 × (MRI tumor size [mm]) + 8.4277.

Conclusions: Our equation may aid accurate preoperative assessment. Further studies are needed to determine its predictive value and applicability.
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http://dx.doi.org/10.1186/s12957-020-01959-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374879PMC
July 2020

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas.

Hepatobiliary Pancreat Dis Int 2020 Dec 2;19(6):581-589. Epub 2020 Jun 2.

Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 5731191, Japan. Electronic address:

Background: Malignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.

Methods: By using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK.

Results: The median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P < 0.01), whereas that of pSmad3L was 3.4%, 4.3%, and 42.4%, respectively (P < 0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P < 0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P < 0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P < 0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P < 0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05-0.93), 3.83 (range, 0.85-5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0-36.9) and 82.1 (range, 46.2-97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7-30.8) and 90.9 (range 52.9-98.5), respectively (P = 0.02).

Conclusions: pSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.
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http://dx.doi.org/10.1016/j.hbpd.2020.05.007DOI Listing
December 2020

Prognostic impact of mucin spread, tumor cell spread, and invasive size in invasive mucinous adenocarcinoma of the lung.

Lung Cancer 2020 08 29;146:50-57. Epub 2020 May 29.

Department of Thoracic Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. Electronic address:

Objectives: The pathological T descriptor of lung invasive mucinous adenocarcinoma (IMA) is currently defined according to mucin spread, whereas that of lung non-mucinous adenocarcinoma is defined according to invasive lesion. This study aimed to evaluate and compare the prognostic impact of mucin spread, tumor cell spread, and invasive lesion in patients with lung IMA.

Materials And Methods: Twenty-seven patients with completely resected pT1-4N0M0 IMA were evaluated. The radiological size (RS), mucin spread size (MS), tumor cell spread size (TS), and invasive size (IS) of the primary tumors were determined. Cox proportional hazards models were used to estimate recurrence-free survival (RFS). Because the MS, TS, and IS may be mutually confounding factors, they were evaluated using separate multivariate models including potential prognostic factors identified as significant on univariate analyses.

Results: The median postoperative follow-up time was 4.9 years. TS and IS were significantly smaller than RS by a median of 0.3 cm (p = 0.027) and 1.4 cm (p < 0.0001), whereas MS and RS were not significantly different (p > 0.999). Univariate analyses identified T descriptors defined by MS, TS, and IS as potentially negative prognostic factors, in addition to age >75 years and carcinoembryonic antigen >5 ng/mL. Multivariate analyses revealed that T factors defined by MS, TS, and IS were significant predictors of RFS (p < 0.0001, p = 0.0002, and p = 0.0067, respectively).

Conclusion: MS is a reasonable determinant of the pathological T descriptor of lung IMA. TS and IS are potential candidates, although they remain discordant with RS. If the TS or IS is to be considered a candidate for the pathological T descriptor of lung IMA, the discordance with RS should first be resolved. If IS is used to define pathological T factor, clear criteria for mucinous AIS/MIA with IMA features should be developed.
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http://dx.doi.org/10.1016/j.lungcan.2020.05.030DOI Listing
August 2020

Benefits of Conversion Surgery after Multimodal Treatment for Unresectable Pancreatic Ductal Adenocarcinoma.

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Department of Surgery, Kansai Medical University, Hirakata 573-1010, Japan.

Background: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC.

Methods: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months).

Results: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS.

Conclusion: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.
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http://dx.doi.org/10.3390/cancers12061428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352934PMC
May 2020
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