[Show abstract][Hide abstract] ABSTRACT: Background
Previous studies reported that the incidence of intestinal spirochetosis was high in homosexual men, especially those with Human Immunodeficiency Virus infection. The aim of the present study was to clarify the clinicopathological features of intestinal spirochetosis in Japan with special reference to Human Immunodeficiency Virus infection status and species types.MethodsA pathology database search for intestinal spirochetosis was performed at Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital between January 2008 and October 2011, and included 5265 consecutive colorectal biopsies from 4254 patients. After patient identification, a retrospective review of endoscopic records and clinical information was performed. All pathology slides were reviewed by two pathologists. The length of the spirochetes was measured using a digital microscope. Causative species were identified by polymerase chain reaction.ResultsIntestinal spirochetosis was diagnosed in 3 out of 55 Human Immunodeficiency Virus-positive patients (5.5%). The mean length of intestinal spirochetes was 8.5 ¿m (range 7¿11). Brachyspira pilosicoli was detected by polymerase chain reaction in all 3 patients. Intestinal spirochetosis was also diagnosed in 73 out of 4199 Human Immunodeficiency Virus-negative patients (1.7%).¿ The mean length of intestinal spirochetes was 3.5 ¿m (range 2¿8). The species of intestinal spirochetosis was identified by polymerase chain reaction in 31 Human Immunodeficiency Virus-negative patients. Brachyspira aalborgi was detected in 24 cases (78%) and Brachyspira pilosicoli in 6 cases (19%). Both Brachyspira aalborgi and Brachyspira pilosicoli were detected in only one Human Immunodeficiency Virus-negative patient (3%). The mean length of Brachyspira aalborgi was 3.8 ¿m, while that of Brachyspira pilosicoli was 5.5 ¿m. The length of Brachyspira pilosicoli was significantly longer than that of Brachyspira aalborgi (p¿<¿0.01). The lengths of intestinal spirochetes were significantly longer in Human Immunodeficiency Virus-positive patients than in Human Immunodeficiency Virus-negative patients (p¿<¿0.05).Conclusions
The incidence of intestinal spirochetosis was slightly higher in Human Immunodeficiency Virus-positive patients than in Human Immunodeficiency Virus-negative patients. However, no relationship was found between the Human Immunodeficiency Virus status and intestinal spirochetosis in Japan. Brachyspira pilosicoli infection may be more common in Human Immunodeficiency Virus-positive patients with intestinal spirochetosis than in Human Immunodeficiency Virus-negative patients with intestinal spirochetosis.
[Show abstract][Hide abstract] ABSTRACT: The proband was a 32-year-old man with sparse type of familial adenomatous polyposis with fundic gland and duodenal polyps and congenital hypertrophy of the retinal pigment epithelium without osteoma, dental abnormalities and desmoid tumors. Direct DNA sequencing did not detect germline mutations in any APC exon. However, using the multiplex ligation-dependent probe amplification method, we detected germline deletions of all APC exons. Using dual-color fluorescence in situ hybridization, we identified germline deletion of locus 5q22.1 – 22.2 that includes APC. Analysis of colorectal tumors identified somatic APC mutations in the cluster region in all polyps, but no loss of heterozygosity was detected in any polyp.
Japanese Journal of Clinical Oncology 10/2014; 44(12):1243-1247. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Patients with de novo stage IV and relapsed breast cancer are often treated with the same strategy. However, survival differences have recently been reported between the disease types. Purpose: The aim of this study was to compare outcomes between de novo stage IV disease and relapsed disease and to discuss any differences in prognostic factors between them. Patients and Methods: The subjects were 79 patients with de novo stage IV disease and 213 patients with relapsed disease treated at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, from October 2001 through November 2010. The Kaplan-Meier method was used to estimate overall survival (OS), and the Cox proportional hazards model was used to examine the association between metastatic disease and OS. Results: The median follow-up period was 32 months for de novo stage IV disease and 34 months for relapsed disease. The median OS was 46 months and 43 months, respectively. No significant differences were evident. Identified prognostic factors were performance status and liver metastasis for de novo stage IV disease, and performance status, hormone receptor status, solitary bone metastasis, and disease-free interval for relapsed disease. Conclusion: No differences in outcome were found between de novo stage IV disease and relapsed disease. However, their prognostic factors differed substantially and suggest that different treatment strategies may be warranted for metastatic disease in each type of breast cancer.
Journal of Nippon Medical School 01/2014; 81(3):139-47. · 0.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective. We examined the anatomy of the pancreatic duct system in patients with autoimmune pancreatitis (AIP) from the standpoint of embryological pancreatic primordial. Material and methods. The pancreatic duct system involved in 83 AIP patients was embryologically divided into both ventral and dorsal pancreatic ducts (VD type), only the dorsal pancreatic duct (D type), or only the ventral pancreatic duct (V type). Results. The 83 AIP patients were divided into 62 VD type, 20 D type, and 1 V type. Obstructive jaundice was significantly more frequent in VD type (87%) than in D type (0%; p < 0.01), and abdominal pain was more frequent in D type (24%) than in VD type (2%; p < 0.01). Stenosis of the lower bile duct was detected in 98% of VD type and 15% of D type (p < 0.01). In the 67 patients with involvement of the pancreatic head, only the dorsal pancreatic duct was involved with a normal ventral pancreatic duct in four patients (D type). In the four D-type patients, the pancreatic duct system showed complete pancreas divisum (n = 1), incomplete pancreas divisum (n = 2), or normal pancreatic duct system (n = 1). Stenosis of the lower bile duct was seen in three patients, but was mild, resulting in no obstructive jaundice. Three patients reported abdominal pain and one patient developed acute pancreatitis. Conclusions. We propose a new entity of "autoimmune dorsal pancreatitis" in which only the dorsal pancreas is involved, and involvement of the lower bile duct and obstructive jaundice is rare.
Scandinavian Journal of Gastroenterology 07/2013; 48(7):856-861. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: N (1) ,N (12)-Diacetylspermine (DiAcSpm) is a tumor marker featured by increase in the urine of patients with cancers, including early colorectal cancer, but where and how DiAcSpm is made remains unclear. We aimed to clarify whether colorectal cancer tissues produce increased amounts of DiAcSpm, and if they do, to examine whether tissue DiAcSpm level may serve as a criterion of tissue malignancy. METHODS: Tissue samples were obtained from 140 patients (13 low-grade intraepithelial neoplasia, 98 high-grade intraepithelial neoplasia and 29 colorectal cancer) treated for colorectal cancer and intraepithelial neoplasia at Tokyo Metropolitan Komagome Hospital between November 2007 and April 2011. The DiAcSpm level in cancer and adjacent normal tissue extracts was compared, and its relationship with clinical stages of the diseases was analyzed. RESULTS: DiAcSpm levels were higher in colorectal cancer tissue (p < 0.01, n = 12) and its liver metastasis (p < 0.05, n = 5) than in adjacent normal tissues. The tumor/normal ratio of tissue DiAcSpm content was examined for endoscopically obtained tumor and adjacent normal tissues from patients with intraepithelial neoplasia. The ratio was greater than 1.5 in 38 % (5/13) and 78 % (84/108) of low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia, respectively. CONCLUSIONS: Tissue DiAcSpm levels increase in the tissue of colorectal cancer and also in precancerous lesion, such as high-grade intraepithelial neoplasia. The increase is considered a sign that a tissue is acquiring malignant characteristics. It is likely that the DiAcSpm produced by cancer cells is responsible for the frequent increase in urinary DiAcSpm in early cancer patients.
Journal of Cancer Research and Clinical Oncology 02/2013; · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.
The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.
Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.
To detect PBM without biliary dilatation before onset of gallbladder cancer, we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.
World Journal of Gastroenterology 07/2012; 18(26):3409-14. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of carcinoma in main-duct intraductal papillary mucinous neoplasm (IPMN) is high, and surgical resection is recommended for all patients with a main-duct IPMN.
A main-duct IPMN with typical imagings including protruding lesions in the dilated main pancreatic duct was resected, but the histology was intraductal papillary mucinous adenoma of the pancreas.
It has been reported that the presence of mural nodules and dilatation of MPD are significantly higher in malignant IPMNs. The presented case had protruding lesions in the dilated main pancreatic duct on endoscopic ultrasonography, but the histology was adenoma.
Preoperative distinction between benign and malignant IPMNs is difficult.
World Journal of Surgical Oncology 11/2011; 9:153. · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated predictors for axillary node metastasis at breast surgery after neoadjuvant chemotherapy (NAC) in patients with pre-chemotherapy-sentinel node positive breast cancer.
Eighty-two patients were diagnosed as having positive sentinel lymph node (SLN), who had axillary lymph node dissection (ALND) performed after combination anthracycline/taxan based NAC, between 2002 and 2009.
Eighteen (22.0%) of the 82 patients had residual axillary metastases after NAC. Multivariate analysis revealed that SLNs status before NAC was an important factor in predicting residual axillary metastases. Predictors of residual nodal disease were the number of macrometastases and the percentage (>50%) of positive SLNs in all SLNs. Among a subgroup of hormone-receptor positive and HER2-negative tumors, the risk of residual nodal metastases were high sensitivity of hormone receptor, with more than 50% of tumor cells staining positive for ER and PgR.
Patients with two or more positive SLNs before NAC had a high risk of residual nodal metastasis after NAC.
Gan to kagaku ryoho. Cancer & chemotherapy 10/2011; 38(10):1639-45.
[Show abstract][Hide abstract] ABSTRACT: Estrogens play an important role in the pathobiology of breast cancer. In postmenopausal women, peripheral synthesis of estrogens from adrenal/ovarian androgens, dehydroepiandrosterone (DHEA) or androstenedione (Adione), by estrogen-metabolizing enzymes is important. Besides estrone (E1) and estradiol (E2), androgen metabolites, such as androstene-3β, 17β-diol (Aenediol) or 5α-androstane-3β, 17β-diol (Aanediol), are known to have estrogenic functions, although they have been studied much less in breast cancer. To precisely elucidate steroid metabolism in breast cancer patients and to identify the pathobiological role of estrogenic androgen metabolites, concentrations of DHEA, Adione, Aenediol, Aanediol, E1, and E2 in pairs of serum and tumor tissue from patients with primary breast cancer were measured by liquid chromatography-tandem mass spectrometry. Cell proliferation assays using Aenediol were performed for four breast cancer cell lines. Serous E2 concentration was extremely low in postmenopausal women; however, a marked increase in tumor tissue was observed in hormone receptor-positive cases. E1 concentration, in contrast, was sustained at a higher level, even in postmenopausal serum, and did not increase in tumor tissue irrespective of the hormone receptor status. Dehydroepiandrosterone was most abundant in all samples, and exhibited a similar pattern as Adione and Aenediol. 5α-Androstane-3β, 17β-diol was undetectable in most samples. Androstene-3β, 17β-diol proliferated estrogen receptor-apositive breast cancer cells in the absence of E2. The intratumoral increase of E2, but not E1, in hormone receptor-positive postmenopausal breast cancer tissue, as well as the proliferative role of Aenediol, was elucidated.
Cancer Science 06/2011; 102(10):1848-54. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary squamous cell carcinoma (SCC) and metaplastic squamous cell carcinoma (MSCC) are rare types of breast cancer with specific histological features. They are characterized by rapid progression, a tendency toward cyst formation, and negativity for hormone receptors. Many studies have concluded that SCC of the breast carries a poor prognosis, based on the fact that conventional chemotherapy for ductal carcinoma of the breast is ineffective against SCC. This is a retrospective study of patients in a single center with SCC or MSCC.
We searched the records of the Tokyo Metropolitan Komagome Hospital for patients diagnosed with breast SCC or MSCC between 1979 and 2006. Squamous cell carcinoma was diagnosed when 100% of the malignant cells showed a squamous component (pure SCC) and MSCC was diagnosed when more than 50% of the malignant cells showed a squamous component. We analyzed the clinicopathological features, treatment methods, and outcomes of these patients.
We identified 10 (0.28%) patients with SCC or MSCC from among 3565 patients with malignant breast tumors treated at our hospital during this period. Nine patients had adenocarcinoma with squamous metaplasia, and one had pure SCC. Ultrasound showed a central cystic-necrotic component in seven tumors, and all of the tumors were negative for hormone receptors and HER2. Recurrence developed in two patients with lymph node metastasis, but not in the other eight patients. The 5-year survival rate and median survival time were 85.7% and 97 months, respectively.
Squamous cell carcinoma or MSCC of the breast with features of the triple-negative subtype seems to be associated with a poor prognosis; however, nodenegative patients are likely to have a favorable prognosis.
Surgery Today 03/2011; 41(3):328-32. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An autoimmune pancreatitis (AIP) patient with metachronous and multiple extrapancreatic lesions is reported. Initial symptoms were proptosis, oculomotor deficits, and a visual field deficit of the left eye, and swelling of bilateral lacrimal glands. Swelling of the right salivary gland and elevated serum levels of hepatobiliary enzymes were detected. AIP associated with IgG4-related orbital pseudotumor, IgG4-related sclerosing dacryoadenitis and sialadenitis, and IgG4-related sclerosing cholangitis was diagnosed. All symptoms and lesions improved with steroid therapy. Although an orbital pseudotumor is a rare extrapancreatic lesion of AIP, we should know that AIP patients may describe unusual symptoms such as abnormal visual field.
Internal Medicine 01/2011; 50(8):887-91. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because the prevalence of carcinoma is high in main-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, surgical resection is recommended for all main-duct type IPMNs. This study aimed to investigate the clinical predictors of malignancy and natural history of main-duct IPMNs.
Preoperative clinical characteristics reliably correlated with malignancy in 26 surgically resected patients with main-duct IPMN, and long-term outcome in 20 conservatively followed patients with main-duct IPMN was examined.
Age at diagnosis was significantly older in conservatively followed IPMN patients than in surgically resected IPMN patients. Main pancreatic duct (MPD) dilatation 10 mm or greater and mural nodules were significantly more frequent in malignant IPMNs. Obvious progression of dilatation of the MPD was detected in all 4 conservatively followed patients who developed invasive pancreatic carcinoma. The histology of IPMN at autopsy of 4 conservatively followed patients who died of other causes 21 to 120 months later was adenoma. Seven conservatively followed without malignant findings did not show obvious progression of MPD dilatation.
Although surgical resection is indicated for many main-duct IPMNs, conservative follow-up may be an option for elderly asymptomatic patients with main-duct IPMNs with the MPD less than 10 mm, no obvious mural nodule, and negative cytology.
[Show abstract][Hide abstract] ABSTRACT: Acinar cell carcinoma of the pancreas is a rare neoplasm exhibiting pancreatic enzyme production by the neoplastic cells. It has a highly characteristic cellular arrangement reflecting its acinar derivation, and a definite diagnosis is made based on immunohistochemical and ultrastructural results. Such tumors are often large but rather well circumscribed. Some cases have a cystic appearance due to hemorrhage or necrosis, but a large cystic mass appearing as a pseudocyst is quite rare. We present a large cystic acinar cell carcinoma of the pancreas.
Journal of hepato-biliary-pancreatic sciences. 10/2010; 18(2):292-4.
[Show abstract][Hide abstract] ABSTRACT: We previously identified INT6/eIF3e as a novel regulator of hypoxia-inducible factor 2alpha (HIF2alpha) activity. Small interfering RNA (siRNA)-Int6 adequately stabilized HIF2alpha, even under normoxic conditions, and thereby enhanced the expression of several angiogenic factors in vitro, suggesting that siRNA-Int6 may induce angiogenesis in vivo.
We demonstrated a 6- to 8-fold enhanced formation of normal arteries and veins in the subcutaneous regions of adult mice 5 days after a single siRNA-Int6 application. Subcutaneous fibroblasts were identified as the major source of secreted angiogenic factors that led to the formation of functional vessels during Int6 silencing. Fibroblasts transfected ex vivo with siRNA-Int6 induced potent neoangiogenesis when transplanted into a subcutaneous region of nude mice. Application of siRNA-Int6 promoted neoangiogenesis in the area surrounding the injury in wound healing models, including genetically diabetic mice, thereby accelerating the closure of the injury. HIF2alpha accumulation caused by siRNA-Int6 was confirmed as the unequivocal cause of the angiogenesis by an in vivo angiogenesis assay. Further analysis of the Int6 silencing-induced neoangiogenesis revealed that a negative feedback regulation of HIF2alpha stability was caused by HIF2alpha-induced transcription of Int6 via hypoxia-response elements in its promoter. Thus, siRNA-Int6 temporarily facilitates an accumulation of HIF2alpha protein, leading to hypoxia-independent transcription of angiogenic factors and concomitant neoangiogenesis.
We suggest that the pathway involving INT6/HIF2alpha acts as a hypoxia-independent master switch of functional angiogenesis; therefore, siRNA-Int6 application might be of clinical value in treating ischemic diseases such as heart and brain ischemia, skin injury, and diseases involving obstructed vessels.
[Show abstract][Hide abstract] ABSTRACT: HER2 oncoprotein plays an essential role in breast cancer growth and differentiation. Determination of HER2 status contributes not only to predicting survival but also to selecting the patients for anti-HER2 therapy. HER2 protein expressed in human cancer cells often contains variant forms as well as the full-length wild-type form. In the present study, we investigated the subcellular localization of HER2 protein in 1053 primary breast cancer tissues. HER2 protein was stained by various immunohistochemical methods and studied by immunoelectron microscopy to confirm the intracellular localization. Thirty-four of 1053 specimens showed cytoplasmic staining of the intracellular domain of HER2 protein by the HercepTest and CB-11. In contrast, no immunoreactivity to the antibodies against the extracellular domain was observed. None of the 34 specimens showed amplification of the HER2 protein by fluorescence in situ hybridization. Subsequently, we studied the association of the cytoplasmic expression of HER2 with neuroendocrine differentiation. Interestingly, all 34 specimens had some positive signals of neuroendocrine markers such as synaptophysin, chromogranin A, neuron-specific enolase, and CD56. Although the result is preliminary, it warrants further study on the role of the cytoplasmic variant form of HER2 in breast cancer growth, particularly in the aspect of neuroendocrine differentiation.
Journal of medical and dental sciences 06/2010; 57(2):155-63.
[Show abstract][Hide abstract] ABSTRACT: We investigated the significance of CD24 and CD44 expression for predicting responses to chemotherapy and prognosis in primary breast cancer patients.
Diagnosis of breast cancer was confirmed by core needle biopsy, and immunohistochemical studies were performed. Preoperatively, patients received anthracycline-containing chemotherapy. Expression of CD44 and CD24 was assessed immunohistochemically and the relationship with chemotherapy response and with prognosis was analyzed.
Between 2001 and 2004, 139 women were enrolled in this study. In the correlation analysis, CD24 expression was negatively associated with pathological response to chemotherapy (p = 0.0003). A machine learning technique with an alternating decision tree (ADTree) showed that four logical rules are involved in predicting the response depending on the combination of CD24, HER2, tumor stage, CD44, progesterone receptor, and patient age. In the survival analysis, patients having CD44 (++) showed a significantly favorable prognosis as compared with others (p = 0.0002). A multivariate analysis showed that CD44 expression had an independent prognostic value (p < .0001).
We found a significant correlation between CD44 expression and prognosis and between CD24 expression and response to chemotherapy. CD24 and CD44 expressions would be useful predictive markers, although further studies are needed.
Journal of medical and dental sciences 06/2010; 57(2):165-75.
[Show abstract][Hide abstract] ABSTRACT: Introduction: During laparoscopic cholecystectomy, an enlarged field of vision increases safety and precision, but surgeons often encounter bleeding that can cause difficulties. It is important to prevent and control arterial bleeding from Calot's triangle and the liver bed that results from injury to the deep branch of the cystic artery (DBCA). However, no previous reports have mentioned the layer between the gallbladder and liver through which the DBCA runs. Materials and Surgical Technique: To determine this layer, we investigated the histological findings from consecutive thin-slice (3 mm) blocks in six cases (three cadavers and three patients who underwent extended cholecystectomy). Results: The subserosal layer of the gallbladder wall can be divided into an inner (ss-i) layer, which consists of abundant vasculature and some fibrous tissue, and an outer (ss-o) layer, which consists of abundant fat tissue. DBCA runs through the ss-o layer, far from the ss-i layer in Calot's triangle, and runs toward the gallbladder body and ramifies into several branches that flow into the ss-i layer. Discussion: If the gallbladder is dissected in the layer close to the ss-i layer, as in our standardized procedure, the subbranches of DBCA are transected at the border of the ss-i layer, and most of the DBCA is left within the ss-o layer in Calot's triangle and the liver bed. Knowledge of the anatomy of DBCA is useful to avoid and stop bleeding from the deep part of Calot's triangle and the liver bed.
[Show abstract][Hide abstract] ABSTRACT: The major duodenal papilla (papilla of Vater) is the point where the dilated junction of the bile and pancreatic ducts (ampulla of Vater) enter the duodenum. The ampulla is surrounded by the sphincter of Oddi, which not only controls the flow of bile and pancreatic juice into the duodenum, but also prevents the reflux of duodenal contents, bile and pancreatic juice into the bile and pancreatic ducts.
Digestive surgery 01/2010; 27(2):90-3. · 1.37 Impact Factor