[A Case of Stage â £ Triple Negative Breast Cancer(TNBC)in Which S-1 Was Successful against Armor-Like Infiltration of the Chest Wall].

A 51-year-old female patient visited our department with a complaint of pain in the left breast. She was found to have Stage Ⅳ breast cancer with liver metastasis. The biopsy-based historical diagnosis was triple negative breast cancer(TNBC). Epirubicin plus cyclophosphamide therapy(EC therapy)plus weekly paclitaxel therapy(weekly PTX)was started for the unresectable advanced breast cancer, but infiltration of an armor-like tumor was observed in the chest wall. It was judged that drug resistance had occurred; hence, the treatment was switched to S-1. Subsequently, almost all the chest wall tumors disappeared after 2 months. However, we did not control the disease, and the patient died. We report about the positioning of S-1 with regard to TNBC, including a literature review.

Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature.

BACKGROUND: A pathologic complete response (pCR) can sometimes be induced by intensive or long-term neoadjuvant chemotherapy (NAC). This prognostic research study based on a systematic review of the literature evaluated the impact of a pCR on the long-term survival of gastric cancer (GC) patients. METHODS: Articles were extracted from PubMed and the Japanese medical search engine "Ichu-shi," using the terms "GC," "NAC," and "pCR." Articles were selected based on the following criteria: (1) full-text case report, (2) R0 resection following NAC for locally advanced GC, and (3) pathological complete response in both the primary stomach and in the lymph nodes. A questionnaire regarding the patients' prognoses was sent to the corresponding authors of the articles selected in July 2013. RESULTS: Twenty-four articles met the criteria. Twenty authors responded to the questionnaire. Finally, 22 patients from 20 articles were entered into the present study. The median follow-up time (range) of the survivors was 76 (range 13-161) months. Tumors that were stage III/IV (86%: 19/22) and of an undifferentiated histology (61.9%: 13/21) were dominant. An S1-based regimen was frequently selected for the NAC. All patients underwent R0 resection and D2/D3 lymphadenectomy. The overall survival and recurrence-free survival rates at 3 and 5 years were 96% and 85% and 91% and 75%, respectively. CONCLUSIONS: Although a pCR was a relatively rare event, a high pCR rate would be helpful to select the regimen and courses of NAC, especially when the pathological response rates are similar.

Intrahepatic micrometastases around liver metastases from gastric cancer.

BACKGROUND/PURPOSE: We aimed to clarify the association between the presence of micrometastases around liver metastases from gastric cancer and the results of hepatic resection. In addition, we investigated the influence of E-cadherin and matrix metalloproteinase (MMP)-7 expression on the development of micrometastases. METHODS: Micrometastases around liver metastases were examined microscopically in 31 metastatic liver tumor specimens resected from 17 patients who had undergone hepatic resection for liver metastases from gastric cancer. E-cadherin and MMP-7 expression in the primary gastric tumor, the liver metastases, and the micrometastases were examined immunohistochemically. RESULTS: Hepatic micrometastases were present in around 48% of the liver metastases, accounting for 59% of the patients. The tumor recurrence rate in the remnant liver after hepatic resection was significantly higher, and survival significantly poorer, in patients with such micrometastases than in those without. Micrometastases tended to appear around the liver metastases that had reduced E-cadherin expression. Most of the micrometastases in the lymph ducts and sinusoids showed reduced E-cadherin expression. MMP-7 expression was not correlated with the presence of micrometastases. CONCLUSIONS: About half of the hepatic metastases from gastric cancer had seeded off micrometastases, and the presence of these micrometastases was associated with a poorer result of hepatic resection. Reduced E-cadherin expression in metastatic liver tumors may be associated with the development of micrometastases.

[Advanced gastric cancer showing complete response to neoadjuvant chemotherapy with CPT-11 and S-1-a case report].

We report a case of advanced gastric cancer that showed a complete histological response to neoadjuvant chemotherapy. The patient, a 56-year-old man, was diagnosed as having advanced gastric cancer with lymph node metastases( cT3 cN1 cH0 cP0 cM0, cStageIIIA). He was initially treated with combined neoadjuvant chemotherapy comprising CPT-11+S-1. S-1(120 mg/day)was administered orally for 21 days, followed by CPT-11(130 mg/body)divon days 1 and 15. The primary lesion and lymph node metastases were diminished by 2 courses of chemotherapy, and no serious toxicities were observed. Distal gastrectomy and lymph node dissection(D2)were performed. Only a small ulcer was observed on the resected stomach. Histological examination of the resected stomach and lymph nodes revealed no remaining viable cancer cells. The patient has been doing well without any recurrence for 1 year since the start of treatment.

[Management of colorectal cancer in elderly patients over 80 years old].

AIM: The incidence of colorectal cancer is increasing. Surgery and chemotherapy for elderly patients are also increasing. We evaluated the characteristics of elderly colorectal cancer to clarify issues related to surgical therapy for elderly patients. METHOD: We studied 67 patients (38 men, 29 women) over 80 years old on whom we operated for colorectal cancer from 1990 to 2004. We compared them with 130 patients aged from 70 to 74 who were operated on in the same period, examining clinicopathological factors, operative methods, preoperative morbidity, postoperative complications, chemotherapy and postoperative survival ratio. RESULTS: In the elderly patients aged over 80, the rate of Dukes' B was high, whereas the rate of Dukes' A was high in patients aged from 70 to 74. No significant differences were observed in operative methods for colon cancer but Hartmann's operation and transanal local excision were frequent for rectal cancer in patients aged over 80. The rate of lymph node dissection was low in patients aged over 80 with rectal cancer. A significant difference was observed in lymph node dissection of rectal cancer between patients aged over 80 and those aged from 70 to 74, but there was no significant difference in curative ratio. Preoperative morbidity were recognized in 76% of patients aged over 80. Postoperative complications occurred in 51% of patients aged over 80. There were many cases showing delirium, but no differences in other complications between patients aged over 80 and those aged from 70 to 74. There was no operative mortality in patients aged over 80. CONCLUSION: Even elderly patients can anticipate safe operations without postoperative complications or decreased quality of life, if the appropriate operative procedure is selected with regard to their general condition.

Validation of the 2012 Fukuoka Consensus Guideline for Intraductal Papillary Mucinous Neoplasm of the Pancreas From a Single Institution Experience.

OBJECTIVES: The 2012 Fukuoka consensus guideline has stratified the risks of malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas into "high-risk stigmata" (HRS) and "worrisome feature" (WF). This study aimed to evaluate its clinical validity based on a single institution experience. METHODS: Eighty-nine patients who underwent surgical resection with pathological diagnosis of IPMN were retrospectively studied. RESULTS: High-risk stigmata was significantly correlated with the prevalence of malignant IPMN as compared with WF. The positive predictive values of HRS and WF were 66.7% and 35.7% for branch duct IPMN and 80% and 38.1% for main duct IPMN, respectively. Univariate analysis indicated that all the factors in HRS and WF had statistical significance. Whereas multivariate analysis revealed only enhanced solid component (odds ratio [OR], 50.01; P = 0.008), presence of mural nodule (OR, 73.83; P < 0.001) and lymphadenopathy (OR, 20.85; P = 0.03) were independent predictors. Scoring HRS and WF by different numbers of positive factors resulted in improved predictive value. The area under the curve of HRS score was significantly lower than that of WF or HRS + WF score (0.680 vs 0.900 or 0.902, respectively; P < 0.001). CONCLUSIONS: As supplementary to the 2012 Fukuoka guideline, we suggest that calculating scores of WF and HRS may have superior diagnostic accuracy in predicting malignant IPMN.

Clinicopathologic study of the MIB-1 labeling index (Ki67) and postoperative prognosis for intraductal papillary mucinous neoplasms and ordinary ductal adenocarcinoma.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are pathologically classified as IPMN with low- or intermediate-grade dysplasia, IPMN with high-grade dysplasia, and IPMN with an associated invasive carcinoma. A stepwise carcinogenic pathway has been considered for IPMN. However, it is not obvious when surgical resection should be performed for IPMN. METHODS: We studied the MIB-1 labeling index in cases of IPMN and ordinary ductal adenocarcinoma (ODA). Moreover, IPMN with an associated invasive carcinoma was divided into 2, namely, carcinoma in situ and invasive components, and the respective MIB-1 labeling indexes were examined. RESULTS: The MIB-1 labeling index for IPMN with low- or intermediate-grade dysplasia (1.8%) was significantly lower than those for IPMN with high-grade dysplasia (14.2%), both the carcinoma in situ components (23.1%) and invasive components (19.2%) within the IPMN with an associated invasive carcinoma, and ODA (19.5%; P < 0.0001).The 5-year survival rates after resection were 100% for IPMN with low- or intermediate-grade dysplasia, 83.3% for IPMN with high-grade dysplasia, 53.8% for IPMN with an associated invasive carcinoma, and 10.3% for ODA. CONCLUSIONS: MIB-1 might be useful for the classification of malignant potential in IPMN. Intraductal papillary mucinous neoplasm should be surgically resected when the tumor is diagnosed as IPMN with high-grade dysplasia.

Expression of MUC1 and MUC2 in ampullary cancer.

BACKGROUND: Mucins are high-molecular-weight glycoproteins that play important roles in carcinogenesis or tumor invasion. The authors investigated the expression of mucins in ampullary cancer. METHODS: MUC1 and MUC2 expressions were examined using immunohistochemistry. Tissue samples were obtained from 32 patients with ampullary cancer who underwent resection at Yamagata University Hospital, Japan. The authors classified the cases with ampullary cancer into 2 subtypes--pancreatobiliary type (PB type) and intestinal type (I type)--using H&E, MUC1, and MUC2 staining. Then, the authors made a comparison of the clinicopathologic data of the 2 subtypes. RESULTS: Fourteen patients (44%) were classified as PB type and 18 patients (56%) as I type. The PB-type group had significantly worse histopathologic characteristics than the I-type group in nodal involvement (PB type 57% vs I type 22%; P = .04), perineural invasion (PB type 50% vs I type 17%; P = .04), duodenal invasion (PB type 100% vs I type 33%; P = .01), and pancreatic invasion (PB type 71% vs I type 33%; P = .03). The PB-type group had significantly worse outcome than the I-type group (5-year survival: PB type 40% vs I type 72%; P = .03). CONCLUSION: PB-type ampullary cancers were more aggressive than I-type carcinomas. MUC1 and MUC2 expression was useful for classification as PB or I type.

Volumetric and morphological analysis of intraductal papillary mucinous neoplasm of the pancreas using computed tomography and magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to predict the malignancy of intraductal papillary mucinous neoplasm (IPMN) based on data obtained by computed tomography and magnetic resonance imaging. METHODS: Sixty-nine patients with IPMN underwent computed tomography, magnetic resonance imaging, and surgery. The tumors were classified pathologically as IPMN (adenoma), IPMN (in situ carcinoma), and invasive carcinoma derived from IPMN, and analyzed morphologically for the following characteristics: tumor size, main pancreatic duct (MPD) diameter, tumor area, MPD area, tumor volume, MPD volume, and intraductal volume (tumors volume + MPD volume). RESULTS: Main pancreatic duct diameter (P = 0.017) and intraductal volume (P = 0.0013) showed significant differences among IPMN (adenoma), IPMN (in situ carcinoma), and invasive carcinoma derived from IPMN. When IPMN (in situ carcinoma) and invasive carcinoma derived from IPMN were classified as malignant IPMN, an MPD diameter of 6 mm or more and an intraductal volume of 10 cm or more were set as cutoff levels predictive of malignancy using receiver operating characteristic curve analysis. On the basis of these criteria, the sensitivity and specificity for identifying malignancy in MPD were 83% and 59%, and those for intraductal volume were 70% and 73%, respectively. CONCLUSION: Intraductal volume (≥10 cm) determined by volumetric analysis is useful for diagnosis of malignant IPMN.

Clinicopathological significance of cell cycle regulatory factors and differentiation-related factors in pancreatic neoplasms.

OBJECTIVES: The aim of the present study was to compare the expression levels of the cyclins and the differentiation-related factors in pancreatic neoplasms. METHODS: The expression levels of cyclins A and B1, E1A-like inhibitor of differentiation 1 (EID-1), p300, 3'-5'-cyclic sdenosine monophosphate response element binding protein (CREB) binding protein (CBP), and acetylated histone H3 (AcH3) in ordinary ductal carcinoma (ODC) and intraductal papillary mucinous neoplasms (IPMNs) of the pancreas were investigated. RESULTS: More cells positive for cyclin A and EID-1 were present in the ODC than in the IPMNs. Cells positive for both cyclins and EID-1 were observed more frequently in invasive carcinoma derived from the IPMN than from the IP mucinous carcinoma. Multivariate regression analysis revealed that EID-1 and cyclin A overexpressions were independent factors associated with poor prognosis. Overall survival was significantly lower in ODC patients with overexpressions of cyclin A, EID-1, and AcH3 than in those without such overexpressions. There were significant differences in the survival curves between patients with ODC and invasive carcinoma derived from IPMN, regarding high frequency for cyclin A or B1. CONCLUSIONS: These results indicated that the expressions of cyclins A and B1, EID-1, and AcH3 may be correlated with a malignant potential in IPMNs. Invasive carcinoma derived from IPMN may be slow growing as compared with ODC.

Intraductal papillary-mucinous neoplasms of the gastric and intestinal types may have less malignant potential than the pancreatobiliary type.

OBJECTIVES: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are classified into 4 types--gastric, intestinal, pancreatobiliary, and oncocytic--on the basis of their morphology and immunohistochemistry. We classified IPMNs at our institute and used this classification to determine the clinicopathological features, prognosis, and malignant potential of the 4 types. METHODS: Sixty-one patients with IPMN who underwent surgery between 2000 and 2007 were evaluated retrospectively. RESULTS: There were 24 tumors of the gastric type, 22 intestinal, 12 pancreatobiliary, and 3 oncocytic. Patients with the intestinal or gastric type had a better prognosis than those with the pancreatobiliary type. The intestinal and pancreatobiliary types had almost the same frequencies of carcinoma, but the intestinal type tended to have a lower frequency of invasive carcinoma than the pancreatobiliary type. Patients with invasive carcinomas derived from intestinal-type IPMNs tended to have a better prognosis than those whose invasive carcinomas were derived from the pancreatobiliary type. CONCLUSIONS: Intraductal papillary-mucinous neoplasm of the gastric and intestinal types may have less malignant potential than that of the pancreatobiliary type. Invasive carcinomas derived from intestinal-type IPMNs may be less invasive and slower growing than those derived from the pancreatobiliary type.

A pancreatobiliary-type carcinoma in situ at the periphery of a mural nodule developed from a gastric adenoma in an intraductal papillary mucinous neoplasm.

We report a rare case of an intraductal papillary mucinous neoplasm (IPMN) with a pancreatobiliary-type carcinoma in situ (CIS) that originated around a mural nodule formed in a gastric-type adenoma. A 64-year-old man was admitted to our hospital in December 2001 for dilation of the main pancreatic duct, detected on abdominal ultrasonography. Branch-duct-type IPMN (diameter 25 mm) was diagnosed, and because mural nodules were absent, the patient was annually followed up for 5 years. In 2006, computed tomography scans revealed thickening of the tumor wall and the development of a mural nodule (diameter approximately 6 mm); pancreatoduodenectomy with regional lymph-node dissection was performed. Histopathologic examination showed an intraductal papillary mucinous carcinoma arising from an adenoma. Hematoxylin and eosin (H&E) staining revealed that most of the tumor components, including the mural nodule, had adenomatous changes, indicating the tumor to be of the gastric type; however, immunohistochemistry showed positive MUC2 expression. Histologically, the tissues around the nodule, including those showing a cribriform pattern, were diagnosed as CIS. These tissues were classified as the pancreatobiliary-type on the basis of the results of both H&E staining and immunohistochemistry. The patient remained disease-free for 3 years after surgery.