The involvement of axillary reverse mapping nodes in patients with clinically node-negative breast cancer.

BACKGROUND: Axillary reverse mapping (ARM) was developed to preserve the lymphatic drainage from the upper arm during sentinel lymph-node (SLN) biopsy or axillary lymph-node dissection (ALND). However, the oncological safety of ARM has been controversial because of not infrequent involvement of ARM nodes. METHODS: Patients with clinically negative nodes (cN0) underwent SLN biopsy and ARM. SLNs were identified using blue dye and radioisotope, and ARM nodes were traced using the fluorescent method. Patients with positive SLN underwent the standard ALND. After surgery, they were followed up for more than 3 years. RESULTS: A total of 507 patients with cN0 breast cancer were enrolled between May 2009 and November 2017. SLNs were identified in 499 (98%) of 507 patients, and ARM nodes were identified in 159 (31%) patients in the SLN field. The crossover rate of SLN-ARM nodes was 28%. Among 95 patients with positive SLNs, 70 patients underwent conventional ALND. ARM nodes were identified in 65 (93%) of those patients in the ALND field. The mean number of removed ARM nodes was 7.2 (range 0-25) in patients who underwent the standard ALND. Although ARM nodes were involved in 18 of 65 patients, the involved ARM nodes were the same SLNs identified in 14 (78%) patients. Since SLN-ARM nodes should be removed, ARM nodes were involved only in 4 (5.7%) patients after SLN biopsy. CONCLUSIONS: Except for positive SLN-ARM nodes, the involvement of ARM nodes is infrequent in patients with positive SLN.

Feasibility of a Clinical Pathway With Early Oral Intake and Discharge for Laparoscopic Gastrectomy.

BACKGROUND AND AIMS: Although some studies have reported the safety of early oral intake after gastrectomy, it still remains controversial. This study focused on the feasibility of a clinical pathway with early oral intake and discharge setting for exclusively laparoscopic distal gastrectomy. MATERIALS AND METHODS: A clinical pathway was applied to 403 patients until December 2014. In the protocol, patients are allowed to take a sip of water and a soft diet on the first and second days after the operation, respectively, and the discharge day is set as the fifth to seventh day after the operation. Clinicopathological variables were prospectively collected, and risk factors for discharge variances were analyzed. RESULTS: The completion rate of the clinical pathway was 76.9%. There were five re-admissions (1.2%). The overall morbidity rate was 18% ( n = 72), and major complications (Clavien-Dindo IIIa or greater) occurred in 13 patients (3%). Complications were the causes for discharge variances in 68 cases (73%), while the attending surgeons' judgment was the cause in 25 cases (27%). On multivariate analysis, age (odds ratio = 2.23, 95% confidence interval = 1.38-3.60, p = 0.001) and operative time (odds ratio = 2.38, 95% confidence interval = 1.45-3.98, p = 0.001) were independent risk factors for discharge variances. CONCLUSION: A high completion rate of a clinical pathway with early oral intake and discharge setting for laparoscopic distal gastrectomy was achievable with an acceptably low re-admission rate. Laparoscopic distal gastrectomy is recommended as a first step for a clinical pathway with an early oral intake and discharge protocol.

Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer

Purpose: Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer. Methods: Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed. Results: High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis. Conclusions: Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients

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Waist-to-height ratio centiles by age and sex for Japanese children based on the 1978-1981 cross-sectional national survey data.

OBJECTIVES: To construct waist-to-height ratio (WC/Ht) reference values and centile curves for Japanese children and to compare these references with those from other countries. METHODS: The 1978-1981 national survey data were used for reference and the 1992-1994 national survey data were used for validation. The former included 19 233 children, and the latter included 10 446 children, aged 6 to 18 years. Waist circumferences (WC) were measured at the level of maximum waist narrowing in girls, and at the level of the top of the iliac crest in boys. Age- and sex-specific reference curves were fitted with the LMS method. Cut-off points were arbitrarily set at 85th, 90th, 95th and 97th centiles, and compared with WC/Ht 0.50. RESULTS: The proportion of children in whom WC/Ht exceeded 0.50 was 18.7% of boys and 1.9% of girls, whereas the proportion of children exceeding 90th centile was 42.4% for boys and 17.3% for girls. The reference values decreased with age in girls but varied by age without a clear trend in boys. CONCLUSIONS: The first reference values for WC/Ht are provided for Japanese youth based on the 1978-1981 national survey data. These curves are age- and sex-dependent, precluding the use of universal cut-off for WC/Ht of 0.50.

Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer.

PURPOSE: Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer. METHODS: Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed. RESULTS: High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis. CONCLUSIONS: Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients.

Severe veno-occlusive disease/sinusoidal obstruction syndrome after deceased-donor and living-donor liver transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.

Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy: reliable results following long-term follow-up.

BACKGROUND: To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. METHODS: From January 1999 to March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. RESULTS: Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83-1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. CONCLUSIONS: Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.

Lymphotropic hepatitis C virus has an interferon-resistant phenotype.

Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B-cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)-based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non-RVR, sustained viral responder (SVR) vs non-SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non-RVR, non-SVR and NVR groups. Association between the therapy outcome and the positive B-cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B-cell HCV RNA and the minor single-nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN-sensitivity determining region were associated with higher levels of B-cell HCV RNA. B-cell-tropic HCV appears to have an IFN-resistant phenotype. B-cell HCV RNA positivity is a predictive factor for resistance to IFN-based therapy.

Relation between outcomes and localisation of p-mTOR expression in gastric cancer.

The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2-4, P=0.003), involved lymph nodes (P=0.010), and tumour stage (I vs II-IV, P=0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (P<0.001,=0.035, and <0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P=0.037) and overall survival (OS, P=0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P=0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer.

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer.

We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT-PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT-PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT-PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

Sotos syndrome with enamel hypoplasia: a case report.

A rare case of Sotos syndrome with enamel hypoplasia is described. Dental abnormalities include enamel hypoplasia, expansion of the pulp cavity, high arched palate, and absence of the bilateral pre-molar teeth of the mandible.

Expression of cathepsin B and cystatin C in human breast cancer.

Cathepsin B, which was originally found to be a lysosomal cysteine protease, is also an important matrix protease. In this study, we investigated the expression of cathepsin B and cystatin C, the strongest inhibitor of cathepsin B, and measured the relative amounts of each in human breast cancer tissues. Cystatin C expression relative to cathepsin B expression was found to be decreased. This finding could be associated with the looseness of cancerous interstitial tissue, which might play a role in cancer invasion and metastasis. This report documents the first simultaneous investigation of cathepsin B and cystatin C in breast cancer tissues.

Expression of hsp90 and cyclin D1 in human breast cancer.

The integral roles of heat shock proteins (hsps) in the cell cycle and in multistep processes leading to tumorigenesis have been implied. We examined the expression of hsp90alpha, hsp90beta and cyclin D1 in human breast cancer. Levels of mRNAs coding for hsp90alpha and cyclin D1 were significantly higher in cancer tissues than in non-cancer tissues. Moreover, there was a close relationship between the extent of the two mRNA levels, suggesting that increased expression of hsp90alpha, an isoform of the hsp90 family, is associated with the proliferation of human breast cancer. Hsp90beta was expressed in cancer cells, but not associated with cell proliferation.

Genotype configuration in a case of primary gastric lymphoma with T-cell phenotype.

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-beta and -gamma genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

[Anesthesia for funnel chest operation].

The incidence of perioperative complication and days of hospital stay were studied in 56 patients with funnel chest operation under inhalational anesthesia (18 cases), intravenous anesthesia (23 cases) and epidural anesthesia (15 cases). Perioperative complication occurred most frequently in the inhalational group and was followed by intravenous and epidural group. Postoperative hospitalization on an average was 21.4 days in the inhalational group, 21.9 days in the intravenous group and 16.7 days in the epidural group. It is said that postoperative pain leads to splinting of the chest, which can cause atelectasis and/or pneumonia. Severe postoperative pulmonary complication was reduced in the epidural groups. As a result, hospitalization in the epidural group was shorter than in other groups. This study suggests that epidural anesthesia is more advantageous for funnel chest operation because epidural anesthesia has protective action against arrhythmia and postoperative pulmonary complication.

[Interstitial vascular reaction of naturally occurring mammary adenocarcinoma in old C3H/HeJ female mice].

Angiogram by soft-X-ray and giant histo-sections were used to investigate the interstitial vascular architectures and correlation between vascular reaction and histologic types of naturally occurring mammary adenocarcinoma in old C3H/HeJ female mice. The tumors were diagnosed as adenocarcinoma B type (Dunn's classification) composed of three different histologic types: solid, comedo, and papillomatous. From the findings of the angiograms, the interstitial vascular architectures of the tumor were classified into three patterns: sinusoidal, hypovascular, and hypervascular. The vascular patterns was characteristic in each histologic type and showed a close correlation with the intensity of tumor proliferation. The fine intratumoral angiographic investigation also made clear that necrosis of tumor cells and tissues seen in the histologic types showing marked proliferation was caused by hypoxia. Application of these methods to investigation of the fine vascular architecture in tumors may useful in research for adenocarcinoma.

Identification of the interplexiform cell in the dace retina by dye-injection method.

The responses of interplexiform cells in the dace retina were recorded intracellularly and identified morphologically. The response pattern closely resembles the response of bipolar cells and amacrine cells (on- and off-types). Morphologically, the perikaryon of most of these cells lies in the amacrine cell layer, and is usually large in size. Distal and proximal processes arise from the soma directly. The distal process ramifies and extends widely in the outer plexiform layer, but does not make contact with receptor terminals. The proximal process branches and extends widely in the inner plexiform layer. The majority of these cells resembles the dopaminergic interplexiform cells, but a few resemble the glycinergic interplexiform cells in the goldfish retina.