Dietary salt concentrations influence growth, nutrient utilization, and fatty acid profiles of turbot (Scophthalmus maximus) reared in brackish water.

Expansion of economically viable turbot (Scophthalmus maximus) aquaculture depends on access to brackish-cold ground water sources in various parts of the world. Since brackish water sources can adversely affect the physiology and zoo technical performance of fish due to the burden of osmoregulation, dietary salt inclusion can alleviate the negative impacts of low-saline waters in several aquaculture species. This study investigated the effects of increasing dietary salt levels on the growth, feed utilization, body composition, and tissue fatty acid composition of juvenile turbot (initial live weight 120.3 ± 0.03 g/fish). Fish were fed five experimental diets supplemented with varying levels of sodium chloride (1.8-6.4%) or a control diet without salt. Each diet was tested in triplicate tanks for 9 weeks. Results showed that increasing dietary salt intake negatively impacted turbot performance, with significant reductions in weight gain, specific growth rate, and feed conversion ratio. Dry matter and ash content in the whole body and filet increased quadratically with increasing salt levels, whereas gill moisture and protein content decreased linearly. Furthermore, the nitrogen, lipid, and energy utilization efficiencies decreased with their respective intake and gain levels. Dietary salt significantly influenced the fatty acid profiles of gill, liver, and filet tissues. In the gill, monounsaturated fatty acids (16:1n-7, ΣMUFA) and n-6 PUFA (20:2n-6) increased, whereas EPA and DHA decreased. Liver ΣSFA (16:0, 18:0) increased, and n-3 PUFA (18:3n-3, 20:5n-3) decreased with increasing dietary salt. Filet saturated fatty acids (14:0, 15:0, 17:0) and n-6 PUFA (20:2n-6, 20:4n-6) increased, while n-3 PUFA (18:3n-3, EPA) decreased with dietary salt. DHA levels in filets showed a quadratic increase. Overall, this study shows that increasing dietary salt negatively impacts turbot growth, feed utilization, and tissue fatty acid composition in brackish water, highlighting the need for further studies on salinity management strategies for turbot aquaculture.

Evaluation of totally implantable central venous access devices with the cephalic vein cut-down approach: Usefulness of preoperative ultrasonography.

BACKGROUND: The aims of this retrospective study, were to evaluate totally implantable central venous access device (TICVAD) implantation and to validate the efficacy of preoperative ultrasonography. METHODS: A total of 380 cases implanted with TICVADs were divided into four groups: cut-downs with ultrasonography (group A, n = 112); cut-downs without ultrasonography (group B, n = 37); venous puncture (group C, n = 122); and replacements using the existing catheter (group D, n = 109). Operation time, completion rate, and complications were compared. RESULTS: The average operating time was 41.7, 52.4, and 40.6 min in groups A, B (P < 0.01), and C, respectively. Group A and B experienced no postoperative pneumothorax, arterial puncture, or pinch-off syndrome. Completion rates were 93.7% in group A and 86.5% in group B. Preoperative ultrasonography identified the cephalic vein in 94.1% of subjects with an average diameter of 3.1 mm and depth of 10.2 mm. Identifying convergence of the cephalic vein and the axillary vein improved the completion rate. CONCLUSIONS: This study showed that the cephalic vein cut-down approach for TICVAD implantation reduced complications. Preoperative ultrasonography resulted in a shorter operating time and higher completion rate.

Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid.

Oncocytic follicular adenomas (FAs) of the thyroid are neoplasms of follicular cell origin that are predominantly composed of large polygonal cells with eosinophilic and granular cytoplasm. However, the pathological characteristics of these tumors are largely unexplored. Both the initiation and progression of cancer can be caused by an accumulation of genetic mutations that can induce genomic instability. Thus, the aim of this study was to evaluate the extent of genomic instability in oncocytic FA. As the presence of p53-binding protein 1 (53BP1) in nuclear foci has been found to reflect DNA double-strand breaks that are triggered by various stresses, the immunofluorescence expression pattern of 53BP-1 was assessed in oncocytic and conventional FA. The association with the degree of DNA copy number aberration (CNA) was also evaluated using array-based comparative genomic hybridization. Data from this study demonstrated increased 53BP1 expression (i.e., "unstable" expression) in nuclear foci of oncocytic FA and a higher incidence of CNAs compared with conventional FA. There was also a particular focus on the amplification of chromosome 1p36 in oncocytic FA, which includes the locus for Tumor protein 73, a member of the p53 family implicated as a factor in the development of malignancies. Further evaluations revealed that unstable 53BP1 expression had a significant positive correlation with the levels of expression of Tumor protein 73. These data suggest a higher level of genomic instability in oncocytic FA compared with conventional FA, and a possible relationship between oncocytic FA and abnormal amplification of Tumor protein 73.

Germline mutations causing familial lung cancer.

Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic 'candidate' mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method.

We developed an easy, quick and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Validation of the prognosis of patients with ER­positive, HER2­negative and node­negative invasive breast cancer classified as low risk by Curebest™ 95GC Breast in a multi­institutional registry study.

Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.

Protocol for studying the efficiency of ChemoCalc software in helping patients to understand drug treatment costs for breast cancer: A multicenter, open-label, randomized phase 2 study.

Survival of patients with breast cancer can be prolonged by treatment with drugs, particularly new molecular-targeted drugs. However, these agents can be expensive and such treatments can be "an economic burden." In this ongoing trial, we aim to assess the usefulness of ChemoCalc, a software package for calculating drug costs, to help patients understand the financial outlays. In this multicenter, randomized controlled phase 2 trial, 106 patients with advanced breast cancer will be assigned to either the "ChemoCalc" or "Usual Explanation" group. Treatment using ChemoCalc will be discussed with patients in the ChemoCalc group, whereas standard treatments, without using ChemoCalc, will be discussed with patients in the Usual Explanation group. Subsequently, the participants will decide the treatment and complete a five-grade evaluation questionnaire; those in the Usual Explanation group will receive information about ChemoCalc. Investigators will report if patients subsequently decide to change treatments. The primary endpoint will be the scores of two key questions compared between the groups: "Did you understand the cost of treatment in today's discussion?" and "Do you think the cost of treatment is important in choosing a treatment?". The secondary endpoints will be to compare discrepancies between treatments recommended by physicians and those selected by patients, the time required for discussion, other questionnaire factors, and the relationship between Comprehensive Score for Financial Toxicity tool and treatment selection. This will be the first randomized controlled trial to assess the efficacy of software to help patients understand drug cost estimates and whether it subsequently affects treatment choice. This study will be conducted according to the CONSORT statement. All participants will sign a written consent form. The study protocol was reviewed and approved by the Clinical Research Review Board of Nagasaki University (19070801). The protocol (version 1) was designed and will be conducted in accordance with the Declaration of Helsinki (1964) and the Ethical Guidelines for Medical and Health Research Involving Human Subjects (2017). The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000039904. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041968.

The history, present situation, and future directions of neoadjuvant chemotherapy for HER2-negative breast cancer.

Chemotherapy has played a significant role in breast cancer therapy and dramatically improved the outcome of breast cancer patients. Neoadjuvant chemotherapy (NAC) is defined as chemotherapy conducted before surgery. The rationale for NAC in operable breast cancer is that the benefit of systemic chemotherapy on the long-term prognosis does not change, regardless of whether chemotherapy is conducted before or after surgery. NAC is now widely used for early and advanced breast cancer patients since it has two significant advantages over conventional adjuvant chemotherapy after surgery. One is that the rate of the breast-conserving surgery increase resulted from tumor shrinkage during NAC, which can contribute to a minimal invasion from surgical therapy and good quality of life following therapy. Another is that a response to chemotherapy can be observed in in-vivo setting. Patients who achieve the pathological complete response (pCR) show a favorable prognosis. Thus, the response to NAC can be used as an indicator for personalized medicine. To date, novel agents for NAC have been explored in randomized trials, setting the pCR rate as an endpoint. Also, response- and residual disease-guided therapy have been ready for prime time in daily practice. The author describes the history, current situation, and future direction of NAC for HER2-negative breast cancer in the review article.

Vascular transection using endovascular stapling in hepatic resection.

In anatomical resection of the liver, transection of the hepatic vein or Glisson's pedicle is necessary. We examined the surgical records and outcome of 25 patients who underwent hepatectomy. An endovascular stapler with 35 and 60 mm staples was used for transection of the hepatic vein or Glisson's pedicle, and hepatic parenchyma including vessels. Surgery included also left lateral sectorectomy in 6 patients, right lateral sectorectomy in one, right hepatectomy in 12, left hepatectomy in two and trisegmentectomy in 4. Endovascular stapling was used for transection of hepatic veins (n=25) in all patients and Glisson's pedicle (n=8). No failure of firing occurred during cutting. Injury of an aberrant bile duct occurred in one patient, but none suffered bleeding or bile leakage from the transected parts. Vascular transection using vascular stapler could be performed safely and rapidly during anatomical hepatic resection.

Usefulness and limitation of laparoscopic assisted hepatic resections: a preliminary report.

BACKGROUND/AIMS: We preliminarily examined the characteristics of patients who underwent laparoscopic assisted hepatic resection (LAPH) to clarify its advantages and limitations of this procedure. METHODOLOGY: We examined the demographics, surgical records and outcome in 9 patients undergoing LAPH between 2001 and 2007 by comparing results in 15 patients (control group) who did not undergo laparoscopy before 2000. RESULTS: By comparing the control group, patient demographics were not different. Four patients underwent left lateral sectionectomy and others underwent partial hepatectomy. One patient needed combined resection of abdominal wall and left lateral sector because of direct invasion from a liver tumor. There was no remarkable morbidity or mortality in all patients. Mean operation time in the LAPH group was significantly longer than that in the control group (356 +/- 68 vs. 276 +/- 59 minutes) (p = 0.015), particularly in patients undergoing partial resection. Blood loss was not different between groups. Days of use of pain reliever and hospital stay in the LAPH group was significantly shorter than that in the control group (p < 0.001). These tendencies were similar in each operative procedure. CONCLUSIONS: LAPH can be safely performed even in patients with chronic liver injury and recovery of patients from operation was faster than that by conventional hepatectomy.

A Novel Diagnostic Method for Thyroid Follicular Tumors Based on Immunofluorescence Analysis of p53-Binding Protein 1 Expression: Detection of Genomic Instability.

Background: The preoperative diagnosis of thyroid follicular carcinomas (FCs) by fine-needle aspiration cytology is almost impossible. It was previously demonstrated that p53-binding protein 1 (53BP1) expression, based on immunofluorescence (IF), can serve as a valuable biomarker to estimate the malignant potential of various cancers. 53BP1 belongs to a class of DNA damage response molecules that rapidly localize to the site of DNA double-strand breaks, forming nuclear foci (NF). This study aimed to elucidate the utility of 53BP1 NF expression as a biomarker to differentiate follicular tumors (FTs). Methods: Associations between 53BP1 expression based on IF and histological types of FTs were analyzed using 27 follicular adenomas (FAs), 28 minimally invasive FCs, and 14 widely invasive FCs. Furthermore, the study clarified the relationship between 53BP1 NF and copy number aberrations (CNAs) based on array comparative genomic hybridization, a hallmark of genomic instability (GIN). Results: This study demonstrates differences in 53BP1 NF expression between FA and FC. The incidence of 53BP1 at NF significantly increased with FT progression in the following order: normal follicle < FA < minimally invasive FCs < widely invasive FCs. In contrast, no significant differences were observed in CNAs among the FT samples. Furthermore, there was no significant correlation between CNAs and 53BP1 at NF in FTs. Thus, based on a comparison of these two indicators of GIN, 53BP1 NF (by IF) was better able to estimate the malignancy of FTs compared to CNA (by array comparative genomic hybridization). Interestingly, IF revealed a heterogenous distribution of 53BP1 NF, which occurred more frequently in the invasive or subcapsular area than in the center of the tumor, suggesting intratumoral heterogeneity of GIN in FTs. Conclusions: It is proposed that IF analysis of 53BP1 expression could be a novel diagnostic method to estimate the malignant potential of FTs. Because 53BP1 NF reflect DNA double-strand breaks, it is hypothesized that the incidence of 53BP1 at NF can represent the level of GIN in tumor cells. IF analysis of 53BP1 expression will not only be an auxiliary histologic technique to diagnose FTs accurately, but also a novel technique for preoperative diagnosis using fine-needle aspiration cytology.

Surgical experiences of intraductal papillary mucinous neoplasms of the pancreas at a single Japanese institute: characteristics of malignant histology.

BACKGROUND/AIMS: Characteristics of intraductal papillary mucinous neoplasms of pancreas (IPMN) have been clarified by a worldwide survey and meeting. However, the malignant behavior or prognosis of the disease is not always uniform. METHODOLOGY: We examined the clinicopathologic demographics, surgical records and outcome according to degree of histologic malignancy in 18 IPMN patients between 1994 and 2006. RESULTS: Main duct type was observed in 3 patients, branch duct type in 6, and mixed type in 9. Eight of 18 patients (44.4%) had other malignancies, and other synchronous tumors were observed in the adenoma group. CA 19-9 was increased in invasive carcinomas. The size of the main pancreatic duct and cysts were not correlated with degree of malignancy. Mural nodules were more frequently observed in minimally invasive and invasive carcinomas. Segmental resection or observation was selected in the adenoma group; however, combined resection of main vessels was performed in invasive carcinoma groups. Although 3 of 5 patients with invasive carcinomas had a recurrence and poor patient prognosis, recurrence was not observed in other groups. CONCLUSIONS: Surgical results for IPMN were satisfactory; however, it is necessary to determine the operative indication before the carcinoma becomes invasive as such lesions have a poor prognosis.

Validation of a Novel Diagnostic Kit Using the Semidry Dot-Blot Method to Detect Metastatic Lymph Nodes in Breast Cancer: Distinguishing Macrometastases From Nonmacrometastases.

BACKGROUND: The semidry dot-blot method is a diagnostic procedure for detecting lymph node (LN) metastases using the presence of cytokeratin (CK) in lavage fluid from sectioned LNs. We evaluated 2 novel kits that use newly developed anti-CK-19 antibodies to diagnose LN metastases in breast cancer. PATIENTS AND METHODS: We examined 159 LNs dissected that we sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. Diagnoses on the basis of the kits were compared with pathological diagnoses. RESULTS: Of the 159 LNs, 68 were assessed as positive and 91 as negative in permanent section examination. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. Those of the high-power kit were 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, those for distinguishing macrometastases were 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 minutes, at a cost of less than $30 USD. CONCLUSION: The kits were accurate, fast, and cost-effective in diagnosing LN metastases without the loss of LN tissue.

Cytogenetic analysis of metaplastic squamous cell carcinoma of the breast inter- and intratumoral heterogeneity.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare and generally aggressive disease that accounts for less than 0.1% of all breast carcinomas. Although SCCs have distinct morphological features, their origin and cytogenetic profile are not well understood. METHODS: Five patients with SCC were studied. The tumor area that was predominantly composed of SCC components was macrodissected and DNA was extracted. In three cases, an invasive or noninvasive ductal carcinoma of no special type (NST) component was also present. NST-component DNA was also extracted. The tumor DNA was used for array comparative genomic hybridization analysis using a high-density oligonucleotide microarray. The cytogenetic profile of the SCC components was compared with each other and with the paired NST component in three of the five cases. RESULTS: The cytogenetic profile of the SCC components indicated large intertumoral heterogeneity. There were between 2 and 160 copy number alterations per case, and no common copy number alterations were identified. The cytogenetic profiles of the paired SCC and NST components were similar but not identical. Although, in one case, a larger number of copy number aberrant regions were detected in the SCC component than the NST component. In this case, all the NST component aberrations were present in the SCC component. This implies that the SCC component originated from the NST component. There were no common SCC component-specific aberrations in the three NST-component cases. CONCLUSION: Our results demonstrate the cytogenetic inter- and intratumoral heterogeneity of SCC of the breast. Our comparison of cytogenetic profiles indicated that the SCC component originated from the NST component in one case.

Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.

The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

Intraoperative diagnosis of lymph node metastasis in non-small-cell lung cancer by a semi-dry dot-blot method.

OBJECTIVES: Sublobar resection procedures, such as segmentectomy and wedge resection, can be used for resectable lung cancer when the cancer is small or the condition of the patient is poor. In such cases, intraoperative lymph node (LN) exploration is necessary to avoid incomplete resection of potential N1 or N2 disease. The semi-dry dot-blotting (SDB) method was developed to detect intraoperative LN metastasis as a quick, cost-effective procedure that does not require special technical expertise. This study examined whether SDB can sufficiently identify LN metastasis in lung cancer patients. METHODS: This study prospectively examined 147 LNs from 50 lung cancer patients who underwent surgery at Nagasaki University Hospital between April 2011 and June 2013. The SDB method uses antigen-antibody reactions with anti-pancytokeratin as the primary antibody and detects cancer cells using chromogen. To identify LN metastases, each LN was examined by the SDB method during surgery along with intraoperative pathological diagnosis (ope-Dx) and permanent pathological diagnosis (permanent-Dx). RESULTS: Compared with permanent-Dx, SDB offered 94.7% sensitivity, 97.7% specificity and 97.2% accuracy, while ope-Dx exhibited 84.2% sensitivity, 100% specificity and 98.0% accuracy. For 3 cases, micrometastases were detected by the SDB method but not by ope-Dx. Three LNs from lobar stations showed pseudo-positive results by the SDB method because of the presence of alveolar epithelium. CONCLUSIONS: The SDB method offers acceptably high accuracy in detecting LN metastasis, especially for mediastinal LNs, and represents a potential alternative for the intraoperative diagnosis of LN metastasis, even in the absence of a pathologist.

A novel diagnostic method targeting genomic instability in intracystic tumors of the breast.

BACKGROUND: Even after needle biopsy, the preoperative differential diagnoses of intracystic tumors of the breast are challenging because of their nonspecific radiological characteristics and subtle cytological and histological appearance. The aim of this study is to investigate a novel diagnostic method, targeting genomic instability (GIN) in intracystic tumors of the breast, using tumor DNA from samples obtained by fine-needle aspiration biopsy (FNAB). METHODS: Thirteen consecutive intracystic tumors of the breast, including five cancers and eight benign tumors, were studied. Three FNAB passages per tumor were used for array comparative genomic hybridization (aCGH) analysis to quantify GIN in each tumor. Tumor DNA from the main tumor, taken from formalin-fixed, paraffin-embedded (FFPE) blocks corresponding to FNAB samples, was also analyzed to compare cytogenetic profiles between these sample types. RESULTS: After three FNAB passages, an average of 7.09 µg (0.24-25.0 µg) of DNA was obtained. The quality of the DNA and the aCGH data was excellent, as judged by the mean derivative log ratio spread (DLRSpread) of 0.22 (0.15-0.29). The cytogenetic profiles of paired FNAB and main tumor FFPE samples were highly similar, with an average concordance rate of 97.7 % (81.2-100 %). aCGH analysis from FNAB samples showed significantly more GIN in cancers than in benign tumors, with mean frequencies of aberrant chromosomal regions of 17.5 and 0.34 %, respectively (Wilcoxon's rank sum test, P = 0.0016). CONCLUSIONS: Our novel diagnostic method, which targets GIN, can clearly distinguish cancers from benign tumors of breast intracystic lesions with minimal invasion, thereby avoiding the need for surgical excisional biopsy.

Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection.

An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day.