Taijiro Kosaka

Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer

BackgroundPatients with luminal HER2-negative tumours have a favourable prognosis. However, there is a subpopulation in which poorer outcomes are obtained with endocrine therapy alone. This subpopulation is considered to benefit from chemotherapy. However, the significance of chemotherapy for those with luminal tumours has decreased due to recent changes in treatment strategies. Thus, it is often difficult to determine whether we should recommend chemotherapy to such patients in clinical practice. We investigated Ki67 expression, as a means of predicting the responses of luminal HER2-negative breast cancer patients to neo-adjuvant chemotherapy (NAC), in order to identify a subpopulation that would benefit from these treatments.MethodsWe enrolled 114 luminal HER2-negative breast cancer patients undergoing surgery after NAC. Biomarkers were examined using biopsy specimens obtained prior to treatment, to avoid any chemotherapy-related effects. Chemotherapy effects were determined employing operative specimens and we defined pathological complete response (pCR) as invasive nest disappearance, based only on the primary breast tumour. We applied receiver operating characteristic curve analysis to data from our 114 patients, to investigate Ki67 expression as a predictor of pCR.ResultsThe pCR rate was significantly higher for tumours with high Ki67 expression (p < 0.01) and all patients who obtained pCR remained recurrence-free during the median 58-month observation period. We identified 35% as the Ki67 cut-off value which distinguishes those with a pCR from other cases. Another dataset, comprised of 196 patients with a median 29-month observation period, was recruited for validation. Disease-free survival was found to be significantly (p < 0.01) lower in the patients with tumours in which Ki67 expression was higher than 35%.ConclusionOur results raise the possibility of the luminal HER2-negative subpopulation with Ki67 expression higher than 35% benefiting from chemotherapy, as evidenced by improved survival.

Significance of HER2 Protein Examination in Ductal Carcinoma In Situ

BACKGROUND HER2 expression is routinely checked in ductal carcinoma in situ, as in invasive ductal carcinoma. However, the effect of HER2 status in ductal carcinoma in situ on the development of malignancy and the significance of overexpression of HER2 are still not clear. MATERIALS AND METHODS We experienced 103 cases that were diagnosed as pure ductal carcinoma in situ from operative specimens in the 2-y period from 2006 to 2007. We examined their HER2 status and other markers. We added 38 cases of ductal carcinoma in situ with small invasive disease 5mm or less in diameter as subjects. We also examined how accurately HER2 status in biopsy specimens predicted the existence of an invasive component. RESULTS In pure ductal carcinoma in situ, tumors that were comedo type, high grade, or ER negative showed a high frequency of HER2 overexpression. In cases with small invasion, HER2 expression was higher than that in pure ductal carcinoma in situ. Among cases that were diagnosed as ductal carcinoma in situ by biopsy, 28% had invasive disease in operative specimens. In tumors that were palpable, large, or expressed HER2 3+ in biopsy samples, invasive disease was frequently observed in operative specimens. CONCLUSIONS Overexpression of HER2 in ductal carcinoma in situ might not always be necessary for progression to invasive ductal carcinoma. To clarify the significance of HER2 examination in DCIS, further investigations of the potential for invasive ductal carcinoma and the prognosis are still needed.

Laparoscopic Resection of an Intra-Abdominal Esophageal Duplication Cyst: A Case Report and Literature Review

Duplication of the alimentary tract is a rare congenital malformation that occurs most often in the abdominal region, whereas esophageal duplication cyst develops typically in the thoracic region but occasionally in the neck and abdominal regions. Esophageal duplication cyst is usually diagnosed in early childhood because of symptoms related to bleeding, infection, and displacement of tissue surrounding the lesion. We recently encountered a rare adult case of esophageal duplication cyst in the abdominal esophagus. A 50-year-old man underwent gastroscopy, endoscopic ultrasonography, computed tomography, and magnetic resonance imaging to investigate epigastric pain and dysphagia that started 3 months earlier. Imaging findings suggested esophageal duplication cyst, and the patient underwent laparoscopic resection followed by intraoperative esophagoscopy to reconstruct the esophagus safely and effectively. Histopathological examination of the resected specimen revealed two layers of smooth muscle in the cystic wall, confirming the diagnosis of esophageal duplication cyst.

Application of a 70-Gene Expression Profile to Japanese Breast Cancer Patients.

Background: As data on using MammaPrint®, a 70-gene expression profile for molecular subtyping of breast cancer, are limited in Japanese patients, we aimed to determine the gene profiles of Japanese patients using MammaPrint and to investigate its possible clinical application for selecting adjuvant treatments. Patients and Methods: 50 women treated surgically at our institution were examined. The MammaPrint results were compared with the St Gallen 2007 and intrinsic subtype risk categorizations. Results: Of 38 cases judged to be at intermediate risk based on the St Gallen 2007 Consensus, 11 (29%) were in the high-risk group based on MammaPrint. 1 of the 30 luminal A-like tumors (3%) was judged as high risk based on MammaPrint results, whereas 7 of the 20 tumors (35%) categorized as luminal B-like or triple negative were in the low-risk group. There have been no recurrences to date in the MammaPrint group, and this is possibly attributable to most of the high-risk patients receiving chemotherapy that had been recommended on the basis of their MammaPrint results. Conclusions: Our results indicate that MammaPrint is applicable to Japanese patients and that it is of potential value in current clinical practice for devising individualized treatments.

Postoperative portal vein thrombosis and gastric hemorrhage associated with late-onset hemorrhage from the common hepatic artery after pancreaticoduodenectomy

Portal vein thrombosis (PVT) is a rare but serious postoperative complication of pancreaticoduodenectomy (PD). We reported a case of late-onset postoperative PVT with hemorrhage from the common hepatic artery (CHA) in a 73-year-old man who underwent pylorus-preserving pancreaticoduodenectomy (PPPD) for duodenum papilla cancer, followed by reconstruction using the modified Childs technique. The pancreaticojejunostomy was achieved by end-to-side, 2-layer invagination anastomosis without pancreatic duct stenting. Drain removal and hospital discharge were scheduled on postoperative day (POD) 18, but blood-stained fluid in the drain and sudden hematemesis were noted. Emergency surgery was performed because PVT and imaging findings were suggestive of necrosis of the lifted jejunum. Although no jejunal necrosis was identified during surgery, bleeding from the side of the CHA was detected and the bleeding point was suture-closed to achieve hemostasis. We suspected late-onset postoperative arterial hemorrhage and subsequent hematoma formation, which caused portal vein compression and PVT formation. We chose a conservative treatment strategy for PVT, taking into account the operation time, intraoperative vital signs and blood flow in the portal vein. Despite the complicated postoperative course, he was discharged home in a fully ambulatory state on POD 167.

Occult Breast Lobular Carcinoma with Numerous Circulating Tumor Cells in Peripheral Blood

We experienced a very rare case of occult breast lobular carcinoma with numerous circulating tumor cells in peripheral blood. The diagnosis was very difficult because there were no symptoms of breast cancer and the preceding chief complaints such as general fatigue and weight loss or abnormality of peripheral blood findings were suggestive of a hematological disease. We could make a correct diagnosis of this case by checking the findings of complete blood count and bone marrow biopsy at the same time using immunohistochemistry.

The usefulness of ultrasonography in a ductal carcinoma in situ screening program for Japanese woman.

24 Background: Although varying among areas, the mammogram (MMG) screening rate is very low in Japan as compared to the U.S. at approximately 20% versus nearly 80% in the U.S. On the other hand, rates of ductal carcinoma in situ (DCIS) detection among diagnosed breast cancers differ minimally: 20% in the U.S., and 15% in Japan. This is a small difference considering the difference MMG screening rates. Racial differences have been suggested to be attributable to the organization of screening programs in Japan, which also use ultrasonography (US) breast cancer screening, as well as breast size in Japanese women. METHODS We retrospectively evaluated MMG and US images of 91 DCIS cases, all 91 Japanese women who under underwent surgery between May 2010 and February 2012. US (TOSHIBA Aplio, probe 9MHz) was performed with knowledge of MMG findings. The 91 cases were divided into group with tumor detected by MMG and US (M&U), MMG detection only (M), and US detection only (U). The following parameters were analyzed: US shape (Tumor-forming lesion: TFL, Non-tumor-forming lesion: NTFL, Cystic-forming lesion: CFL), Skin-Muscle distance: SMD. We excluded asynchronous bilateral breast cancers and micro-invasive DCIS. RESULTS Sixty-eight lesions (73.0%) were identified by US, which revealed a NTLF in 52 cases, TLF in 9 cases and CFL in 7 cases. All cases with false-negative findings on US (Group M, n = 23) showed micro-calcifications on MMG (n=22) and with the tumor (n=1). In the U group, SMD was only 23 mm versus 43.4mm in the M group. No difference was observed in body mass index or pathological tumor diameter between the U and M. CONCLUSIONS We found US to reveal DCIS in 73% of our cases upon reevaluation. Although US examination would not likely increase the screening detection rate for DCIS in Japanese women, US may reveal more DCIS in Japanese women, in which the breasts are comparatively small, than in western women. Further comparison of possible racial difference is warranted.

Combined Core Needle Biopsy and Fine Needle Aspiration Cytology UsingReturned Cell Block Method is Effective for Diagnosis of Cystic Lesions ofthe Breast

Background: Core needle biopsy (CNB) and fine needle aspiration cytology (FNAC) are useful methods to diagnose cystic lesions of the breast. The first English article describing the returned cell block method (RCBM: cell block from a Papanicolaou staining smear on a glass slide) was reported by us, and we also reported the usefulness of RCBM for the FNAC-based evaluation of tumors of the breast. In the present study, diagnostic procedures of CNB and FNAC using RCBM for cystic lesions of the breast were studied. Methods: Forty-seven patients with cystic lesions of the breast diagnosed by sonographic examination and sonographically-guided FNAC were evaluated. In all cases, the evaluation of FNAC was performed by Papanicolaou staining smears, and RCBM was added in cases that were difficult to evaluate. The data from CNB (26 cases) and surgery (15 cases) were also evaluated. Results: The accuracy of diagnosing carcinoma of FNAC from Papanicolaou staining smear was 56.2%. The diagnostic accuracy increased to 75% on using RCBM, and the same level of accuracy was found on CNB. In 4 cases, a diagnosis of carcinoma was made by CNB only (2 cases) or FNAC using RCBM only (2 cases). Subsequently, the accuracy increased to 87.5% due to the combination of CNB and FNAC using RCBM. Conclusions: Combined CNB and FNAC using RCBM is effective for the diagnosis of cystic lesions of the breast. Based on this new finding, we propose a procedure to diagnose cystic lesions of the breast by CNB and FNAC using RCBM.