Akio Yanagisawa

Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers.

Background. The presence of lymph node metastasis (LNM) is the most important prognostic factor for patients with early gastric cancer (EGC). A D2 gastrectomy has been the gold standard treatment. Strict criteria for endoscopic mucosal resection have been widely accepted in Japan. There are some trials aimed at expanding the indications for local treatment, although there has not been a comprehensive review of the risk of LNM with the lesions of EGC. Methods. We investigated 5265 patients who had undergone gastrectomy with lymph node dissection for EGC at the National Cancer Center Hospital and the Cancer Institute Hospital. Nine clinicopathological factors were assessed for their possible association with LNM. Results. None of the 1230 well differentiated intramucosal cancers of less than 30 mm diameter regardless of ulceration findings, were associated with metastases (95% confidence interval [CI], 0–0.3%). None of the 929 lesions without ulceration were associated with nodal metastases (95% CI, 0–0.4%) regardless of tumor size. Similarly to findings for intramucosal cancers, for submucosal lesions, there was a significant correlation between tumor size larger than 30 mm and lymphatic-vascular involvement with an increased risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30-mm-diameter without lymphatic or venous permeation were associated with LNM, provided that the lesion had invaded less than 500 μm into the submucosa (95% CI, 0–2.5%). Conclusion. Based on our large series of cases, we have been able to clarify the risks associated with EGC and to propose expansion of the criteria for local treatment. However, accurate histological evaluation of the resected specimens is essential to avoid recurrence for such EGCs that should be cured.

A novel classification system for patients with PTC: addition of the new variables of large (3 cm or greater) nodal metastases and reclassification during the follow-up period

BACKGROUND Several factors have been proven to be useful for classifying patients with papillary thyroid carcinoma (PTC) into either low- or high-risk groups. However, the relative importance of prognostic factors, including lymph nodal metastasis, remains unclear. METHODS A total of 604 patients who underwent initial surgery for PTC (diameter of tumor>1 cm) were analyzed. The mean duration of follow-up was 10.7 years. RESULTS By multivariate analysis for disease-specific survival, distant metastasis was the only significant risk factor (risk ratio=65.1) for younger patients (age<50). For older patients (age> or =50), distant metastasis (risk ratio=6.7), extrathyroidal invasion (risk ratio=2.4), and large nodal metastasis (> or =3 cm; risk ratio=5.3) had relative importance. From the results, younger patients with distant metastasis and older patients with any of the 3 factors were defined as at high risk, whereas the other patients were defined as at low risk. Overall, 106 patients at high risk (18%) and 498 patients at low risk (83%) had 10-year survival rates of 69% and 99%, respectively. Only 3 patients of the low-risk group died from the disease. Among postoperative factors, recurrence within 3 years after initial surgery was the most important risk factor for cancer death. Of the high-risk group, patients with a disease-free interval of >3 years showed an excellent outcome (96% of a 10-year survival rate), similar to patients in the low-risk group. CONCLUSIONS A novel classification system, in which large nodal metastases and postoperative reclassification were added, was devised. This was useful for choosing proper therapeutic strategies, offering rational information, and determining adequate postoperative follow-up schemes for individual patients with PTC.

Cystic neoplasm of the pancreas: a Japanese multiinstitutional study of intraductal papillary mucinous tumor and mucinous cystic tumor.

Abstract: The Japan Pancreas Society performed a multiinstitutional, retrospective study of 1379 cases of intraductal papillary mucinous tumor (IPMT) and 179 cases of mucinous cystic tumor (MCT) of the pancreas. Clinicopathologic features and postoperative long-term outcomes were investigated. IPMT were most frequently found in men and in the head of the pancreas. In contrast, all patients with MCT were women. Ovarian-type stroma were found in only 42.2% of the MCT cases. Prognostic indicators of malignant IPMT included advanced age, positive symptoms, abundant mucous secretion, presence of large nodules and/or large cysts, remarkable dilatation of the main pancreatic duct, and main duct- or combined-type IPMT. Advanced age, positive symptoms, and presence of large nodules and/or large cysts were predictive of malignant MCT. The 5-year survival rate of IPMT patients was 98%–100% in adenoma to noninvasive carcinoma cases, 89% in minimally invasive carcinoma cases, and 57.7% in invasive carcinoma cases. The 5-year survival rate of MCT patients was 100% in adenoma to minimally invasive carcinoma cases and 37.5% in invasive carcinoma cases. In conclusion, IPMT and MCT show distinct clinicopathologic and prognostic differences. The results from this study may contribute to the diagnosis and treatment of IPMT and MCT.

Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version

Diagnostic and treatment strategies for gastrointestinal stromal tumors (GISTs) have evolved greatly since the introduction of molecularly targeted therapies. Although several clinical practice guidelines are extant, such as those published by the National Comprehensive Cancer Network and the European Society of Medical Oncology, it is not clear as to whether these are appropriate for clinical practice in Japan. Therefore, clinical practice guidelines for the optimal diagnosis and treatment of GIST tailored for the Japanese situation have often been requested. For this reason, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee, with the official approval of the Clinical Practice Guidelines Committee for Cancer of the Japan Society of Clinical Oncology (JSCO), and was published after assessment by the Guideline Evaluation Committee of JSCO. The GIST Guideline Subcommittee consists of members from JSCO, the Japanese Gastric Cancer Association (JGCA), and the Japanese Study Group on GIST, with the official approval of these organizations. The GIST Guideline Subcommittee is not influenced by any other organizations or third parties. Revision of the guideline may be done periodically, with the approval of the GIST Guideline Subcommittee, either every 3 years or when important new evidence that might alter the optimal diagnosis and treatment of GIST emerges. Here we present the English version of the Japanese Clinical Practice Guideline for GIST prepared by the GIST Guideline Subcommittee.

Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society.

Objective: The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs). Materials and Methods: We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated. Result: Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN. Conclusions: Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: a multicenter study in Japan.

Objective: The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan. Methods: We analyzed 349 follow-up BD-IPMN patients who had no MNs on endoscopic ultrasonography at initial diagnosis. Results: Observation periods ranged from 1 to 16.3 years (median, 3.7 years). Sixty-two (17.8%) patients exhibited disease progression during follow-up. Twenty-two underwent surgery, leading to a pathological diagnosis of carcinoma in 9 and adenoma in 13. Although the remaining 287 (82.2%) showed no changes, 7 underwent surgery because of symptoms (n = 2), choice (n = 2), or development of pancreatic ductal adenocarcinoma (n = 3); all of them were diagnosed pathologically as adenomas. Of the 29 patients undergoing surgery, all 9 with carcinoma exhibited signs of progression, such as increased main pancreatic duct diameter and/or appearance of MNs. Pancreatic ductal adenocarcinomas and additional BD-IPMNs developed in 7 (2.0%) and 13 (3.7%), respectively. Overall, 320 (91.7%) patients were followed without surgery. Conclusions: Most BD-IPMN patients who had no MNs on endoscopic ultrasonography could be managed without surgery. However, careful attention should be paid to disease progression and the development of pancreatic ductal adenocarcinomas during follow-up.Abbreviations: IPMN - intraductal papillary mucinous neoplasm, BD-IPMN - branch duct intraductal papillary mucinous neoplasm, MD-IPMN - main duct intraductal papillary mucinous neoplasm, MN - mural nodule, MPD - main pancreatic duct, PDA - pancreatic ductal adenocarcinoma, US - ultrasonography, ERCP - endoscopic retrograde cholangiopancreatography, MRCP - magnetic resonance cholangiopancreatography, EUS - endoscopic ultrasonography, CT - computed tomography

Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid.

Abstract. Although anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, a few patients survive for a fairly long time after modern intensive treatment. We tried to identify prognostic factors of ATC to assist in deciding on the proper therapeutic strategy in individual patients. Of 47 patients with ATC (1976–1999), 3 patients with “incidental” ATC (largely differentiated thyroid carcinoma with a small region of ATC) were excluded because they had a favorable outcome. The 1-year survival rate of the remaining 44 patients with clinically distinct ATC was 16%. The presence of acute symptoms, large tumor (> 5 cm), distant metastasis, and leukocytosis (white blood cell count ≥ 10,000/mm3) proved to be significant risk factors. Multivariate analysis by the Cox proportional hazard model showed that these four factors were independent factors for predicting death from ATC. We devised a novel prognostic index (PI) based on the number of these four unfavorable characteristics the patient possessed. Patients with a PI of ≤1 had a 62% survival rate at 6 months, whereas no patients with a PI of ≥3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Nine patients received multimodal treatment with a combination of surgery, external irradiation, and chemotherapy and had a long survival (mean 333 ± 68 days; one patient is still alive and tumor-free), with a mean PI of 0.6. Our PI is useful as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results; if it is high most patients are too seriously ill to tolerate intensive treatment and palliative therapy is recommended.

Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus April 2012 edited by the Japan Esophageal Society

Purpose These guidelines are intended for doctors who are engaged in the diagnosis and treatment of esophageal carcinoma, for the following purposes: (1) to present the standard practice for the diagnosis and treatment of esophageal carcinoma with a high regard for the principles of evidence-based medicine (EBM); (2) to improve the safety and results of treatment, thereby reducing the difference in treatment results among different institutions; (3) to reduce unnecessary costs and efforts; (4) help enable people to undergo treatment without anxiety. These guidelines provide only guidance on the indications for treatment and do not restrict or prohibit the use of any treatment deviating from those described herein.

Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms

BACKGROUND AND STUDY AIMS Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs), and associated synchronous and metachronous pancreatic cancers are increasingly detected as imaging modalities become more sensitive. We investigated the natural history of SB-IPMN, and the incidence and characteristics of pancreatic cancers among patients undergoing long-term follow-up. PATIENTS AND METHODS We reviewed the clinical, imaging, and pathological features in 103 patients, diagnosed at the Aichi Cancer Center between September 1988 and September 2006 as having SB-IPMN, and conservatively followed up for ≥ 2 years (median 59 months) based on an endoscopic ultrasonography (EUS) database. RESULTS 74 (71.8 %) patients had nonprogressive lesions. Overall, six patients (5.8 %) developed pancreatic cancers during follow-up, with intraductal papillary mucinous (IPM) carcinoma in four, and ductal carcinoma of pancreas that was not IPMN in two patients. Of the six pancreatic cancers, five were diagnosed at a resectable stage. The 5-year and 10-year actuarial rates of development of pancreatic cancer were 2.4 % and 20.0 %, respectively. Although, at the last follow-up, cyst size, main pancreatic duct (MPD) diameter, mural nodule size, and frequency of metachronous and/or synchronous cancers of other organs were significantly higher in patients who developed IPM carcinoma, resected SB-IPMNs without mural nodules and dilated MPDs had no IPM carcinomas. CONCLUSIONS The frequency of pancreatic cancers is high on long-term follow-up of SB-IPMN. Although conservative management is appropriate for selected patients, regular and long-term imaging, especially by EUS is essential, even if SB-IPMN remains unchanged for 2 years. Presence of mural nodule and dilated MPD seem to be more appropriate indicators for resection than cyst size alone for SB-IPMNs.

Japan Pancreatic Cancer Registry; 30th year anniversary: Japan Pancreas Society.

Objectives Since 1981, the Japan Pancreas Society has been hosting a nationwide pancreatic cancer registry. To commemorate its 30th anniversary, we review its history and latest achievement. Methods During 3 decades, more than 350 leading institutions in Japan contributed voluntarily to register and periodic follow-up. The registry was modified to protect privacy by encrypting and hash algorithm. Results From 1981 to 2007, 32,619 cumulative records were analyzed. The overall survival of invasive cancer was improved significantly. More patients with earlier stage or with intraductal and cystic neoplasms underwent resection. The strongest prognostic factor of Union for International Cancer Control (UICC) stage IIA and IIB tubular adenocarcinoma in the pancreatic head was histological grade, followed by tumor size, extent of lymph node dissection, and postoperative chemotherapy. The 5-year survival rate of Union for International Cancer Control stage 0 reached 85%. The improvement of survival of patients with invasive cancer in Japan can be attributed to the introduction of effective chemotherapies, regionalization, and the earlier diagnosis and treatment. Simple definition of “early pancreatic cancer” is needed. Conclusions At the 30th year anniversary, the Japan Pancreas Society nationwide pancreatic cancer registry is more shining than ever for current perspectives and for future diagnostic and treatment tactics.