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Eto T.,National Kyushu Cancer Center | Saito T.,National Kyushu Cancer Center | Kasamatsu T.,National Cancer Center Hospital | Nakanishi T.,Aichi Cancer Center Hospital | And 6 more authors.
Gynecologic Oncology | Year: 2012

Objective: To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA). Methods: The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS). Results: The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases. Conclusions: Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases. © 2012 Elsevier Inc.


Tsuda H.,National Cancer Center Hospital | Tsuda H.,National Defense Medical College | Kurosumi M.,Saitama Cancer Center Hospital | Umemura S.,Tokai University | And 3 more authors.
BMC Cancer | Year: 2010

Background: Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens.Methods: A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic.Results: In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ versus 2+ versus 3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ versus 3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at different institutions.Conclusion: It is mandatory to study HER2 on breast cancers, and either CNB or surgical specimen can be used. © 2010 Tsuda et al; licensee BioMed Central Ltd.


Kikuchi I.,Saitama Cancer Center Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012

We report a rare case of a 78-year-old woman with metachronous axillary lymph node metastasis originating from descending colon cancer. Her past medical history included right mastectomy for breast cancer at age 53 and distal gastrectomy for gastric cancer at age 70. She underwent a left hemicolectomy for descending colon adenocarcinoma in April 2011. Four months after that operation, 3 enlarging nodules in the left lung and a swollen left axillary lymph node were detected by computed tomography. No tumor was detected in the left breast by ultrasonography and mammography. The lung tumors were resected thoracoscopically, and the left axillary lymph node was excised. These specimens were histologically diagnosed as moderately differentiated adenocarcinoma, which had metastasized from colon cancer, not from the previous breast or gastric cancer. She received adjuvant chemotherapy with uracil and tegafur (UFT) plus Leucovorin for 6 months and is still alive after 12 months without recurrence.


Yamaura T.,Saitama Cancer Center Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2011

The patient was a 77-year-old woman. She was diagnosed as intraducal papillary mucinous neoplasms (IPMN). She refused an operation for 3 years. After all, a nodule in the main pancreatic duct was pointed out, she agreed and was referred to us. Her past history showed pacemaker implantation for third-degree atrioventricular block, and no impaired glucose tolerance. Abdominal CT showed a dilated whole pancreatic duct and a multilocular cystic tumor. Endoscopic retrograde pancreatography showed a marked dilation of the main pancreatic duct. We diagnosed as main duct IPMN. Intraoperative US showed no nodule in pancreatic duct, and there was no suspicious lesion of invasive cancer. We performed segmental pancreatectomy between the left side of common bile duct and the pancreas tail. The tumor was resected with clear margins. Both cut-ends of the main pancreatic duct were anastomosed to a jejunal loop. The postoperative course was excellent. She was discharged on day 16. The glycemic control was good, she needed no treatment for diabetes. Total pancreatectomy has many problems such as insulin and pancreatic polypeptide deficiency, hypoglycemia, malabsorption, diarrhea and liver dysfunction. We avoided total pancreatectomy so that her quality of life was maintained. Still a careful follow -up is required.


Yamaguchi K.,Saitama Cancer Center Hospital | Watanabe T.,University of Tokyo | Satoh T.,Kinki University | Satoh T.,Osaka University | And 5 more authors.
Japanese Journal of Clinical Oncology | Year: 2014

Objective: Infusion reactions are common adverse reactions associated with antibody preparations. However, no studies have examined the time to onset of serious infusion reactions after administering cetuximab. We aimed to investigate the timing and severity of IRs affecting Japanese patients after administration of cetuximab. Methods: Study subjects were identified from a nationwide prospective registry of 2126 metastatic colorectal cancer patients scheduled to receive cetuximab. Infusion reactions were examined in 2006 patients with adequate safety data. Results: Infusion reactions of any grade occurred in 114 patients (5.7%), including Grade 3-4 infusion reactions in 22 patients (1.1%). Premedications were antihistamine plus corticosteroid (88.9% of patients with infusion reactions), antihistamine alone (9.2%) or corticosteroid alone (1.1%). In 95 patients (83.3%), infusion reactions occurred after the first dose. Twenty of the 22 Grade 3-4 infusion reactions occurred within 1 h of the first dose (the timing of the infusion reaction was unknown in one patient while another infusion reaction occurred after the fourth dose). Infusion reactions resolved in 111/114 patients (97.4%) while one patient recovered with sequelae, one patient died and one patient failed to recover within the follow-up period. Thirteen patients (15.7% of patients with infusion reactions) with Grade 1-2 infusion reactions showed recurrence after readministration of cetuximab; the recurrent infusion reactions were less severe than the initial reactions. Conclusions: Grade 3-4 infusion reactions occurred in 1.1% of colorectal cancer patients, and most occurred within 1 h of receiving the first dose of cetuximab. Therefore, patients should be carefully observed following cetuximab infusion, especially during the first hour after the first infusion. © The Author 2014. Published by Oxford University Press.


Watanabe T.,Research Institute for Clinical Oncology | Takahashi A.,Research Institute for Clinical Oncology | Takahashi A.,Saitama University | Suzuki K.,Research Institute for Clinical Oncology | And 4 more authors.
International Journal of Cancer | Year: 2014

Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis. © 2013 UICC.


Okano W.,Saitama Cancer Center Hospital | Okano W.,National Cancer Center Hospital East | Hayashi R.,National Cancer Center Hospital East | Omori K.,Fukushima Medical University | Shinozaki T.,National Cancer Center Hospital East
Japanese Journal of Clinical Oncology | Year: 2016

Objective: In this study, we evaluate the management of the thyroid gland in salvage surgery for hypopharyngeal and cervical esophageal carcinoma after radiotherapy or chemoradiotherapy. Methods: We retrospectively reviewed patients who underwent total pharyngolaryngoesophagectomy as salvage surgery between 1998 and 2008. The management of the thyroid gland was evaluated on the basis of stomal recurrence, tracheal necrosis, thyroid and parathyroid functions. Results: Stomal recurrence was not found in patients with piriform sinus and posterior pharyngeal wall carcinoma treated by hemithyroidectomy. Tracheal necrosis occurred in 20% of the patients undergoing total thyroidectomy but in only 2% undergoing hemithyroidectomy. Hypothyroidism occurred in 21% undergoing hemithyroidectomy. Hypoparathyroidism occurred in only 2.6% undergoing hemithyroidectomy. Conclusions: Total thyroidectomy is not always necessary during salvage total pharyngolaryngoesophagectomy for piriform sinus and pharyngeal wall carcinoma. Preservation of the thyroid gland will contribute not only to prevent local complications but also to preserve the parathyroid function. © The Author 2016.


PubMed | Shizuoka Cancer Center, Aichi Cancer Center Hospital, Exploratory Oncology Research and Clinical Trial Center, University of Toyama and 8 more.
Type: Journal Article | Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | Year: 2015

This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancer patients who received standard chemotherapy.Unresectable or recurrent gastric or gastroesophageal junction cancer patients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3+ or an IHC score of 2+/FISH positive for HER2, and an IHC score of 2+ or 3+ for both EGFR and c-MET.Of the 293 patients from nine institutions, 43 (15%) were HER2 positive, 79 (27%) were EGFR positive, and 120 (41%) were c-MET positive. Ten patients (3%) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95% confidence interval, 1.03-1.67); log-rank P = 0.024]. Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95% confidence interval, 1.02-1.67); P = 0.037].The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancer patients.


PubMed | Merck KGaA, Catholic University of Leuven, Saitama Cancer Center Hospital, Nagoya University and Tokyo Electron
Type: | Journal: Clinical colorectal cancer | Year: 2017

Adding cetuximab to FOLFIRI (5-fluorouracil, leucovorin, irinotecan) significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with KRAS or RAS (KRAS/NRAS, exons 2-4) wild-type (wt) metastatic colorectal cancer (mCRC) in the first-line CRYSTAL study. The present exploratory and descriptive retrospective analysis assessed the quality of life (QoL) of CRYSTAL study patients with RAS wt mCRC-the labeled indication for cetuximab in many countries.Patient QoL was investigated using the European Organisation for Research and Treatment of Cancer QoL questionnaire core-30 (EORTC QLQ-C30). QoL assessments were performed at baseline, after every 8 weeks of treatment, and at the final tumor assessment. RAS wt patients were considered evaluable for QoL if they had provided 1 evaluable EORTC QLQ-C30.Of the 367 patients with RAS wt tumors, 351 were evaluable for QoL. Global health status (GHS)/QoL and the time to worsening of Eastern Cooperative Oncology Group performance status were similar between the treatment groups. However, the analysis was complicated by a large decrease in the number of evaluable patients in the FOLFIRI arm between weeks 32 and 40. The individual dimensions of interest in mCRC (eg, social functioning, fatigue, nausea/vomiting, pain, appetite loss, constipation, diarrhea, and functional difficulties) were also similar between the treatment arms. Changes in GHS/QoL and social functioning from baseline to week 8 were similar, irrespective of whether patients experienced early skin reactions.The findings of the present descriptive retrospective analysis suggest that adding cetuximab to first-line FOLFIRI improves PFS, OS, and ORR without negatively affecting the QoL of CRYSTAL study patients with RAS wt mCRC.


PubMed | Niigata Cancer Center Hospital, National Cancer Center Hospital East, National Cancer Center Hospital, Saitama Cancer Center Hospital and 6 more.
Type: Journal Article | Journal: Japanese journal of clinical oncology | Year: 2016

There is little information about the patterns of care for elderly esophageal squamous cell carcinoma patients, and a standardized strategy has not been established. Therefore, we conducted a questionnaire survey about the patterns of care for these patients.On September 2014, the questionnaires were sent to all 43 institutions of the Japan Esophageal Oncology Group, which comprised five parts: (i) definition of elderly (age, method), (ii) basic treatment strategy according to stage and elderly status (fit/vulnerable/frail), (iii) patterns of care in each stage, (iv) considerations about conducting future clinical trials and (v) other information about geriatric oncology concerning esophageal squamous cell carcinoma.All answers were obtained by January 2015. Nearly half institutions (47%) considered the chronological definition of elderly to be over 80 years old. Among 43 institutions, 36 (84%) reported that the type of comorbidity and performance status were important factors for decision-making; no institution selected geriatric scale as an indicator. The most selected treatment strategy in fit healthy elderly patients was the same as the standard treatment of non-elderly patients. Radiation alone was considered the main treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Most of the institutions answered that clinical trials for the elderly are warranted. Most institutions (70%) chose Stage II/III (non-T4) esophageal squamous cell carcinoma as an important investigational target.Fit healthy elderly were considered the same as non-elderly patients, although there are no established treatment selection criteria. Radiation alone plays most important role in the treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Stage II/III (non-T4) disease is attractive and warranted for future investigations.

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