Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics ...remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32,
P
< 0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.
The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors ...amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.
Objective Recognizing that the safety and efficacy of laparoscopic surgery for rectal cancers have not been fully established, we conducted a retrospective study to determine whether the percentage ...of the pelvic cavity occupied by a rectal tumor affects the difficulty of laparoscopic rectal surgery or the occurrence of postoperative complications. Methods Our study involved 100 patients with rectosigmoid (Rs), upper rectal (Ra), or lower rectal (Rb) cancer treated by laparoscopic surgery at our hospital. Pelvic volume (PV), rectal volume (RV), tumor volume (TV), and respective percentages of the pelvic cavity they occupied were determined on the basis of preoperative computed tomography colonography (CTC) reconstruction images. We analyzed the relation between these percentages and the time to resection, blood loss volume, and number of staples used on the rectal stump (as measures of surgical difficulty) and anastomotic leakage (as a postoperative complication). Results Univariate analysis revealed significant differences in age (P = 0.009), PV (P = 0.012), TV (P = 0.042), percentage of the pelvic cavity occupied by the tumor (P = 0.011), and percentage of the pelvic cavity by the tumor and rectum together (P = 0.003) in all patients who developed anastomotic leakage and those who did not. Significant differences were also found in PV (P = 0.029) and in the percentage of the pelvic cavity occupied by the tumor and rectum together (P = 0.041) between the Ra patients in whom anastomotic leakage occurred and those in whom it did not occur. The blood loss volume and number of staples used differed significantly between the high-percentage occupancy group and low-percentage occupancy group (P = 0.050 and P = 0.001, respectively). Further, the number of staples used differed significantly between the high-percentage occupancy Ra group and low-percentage occupancy Ra group (P = 0.019). The data point to increased surgical difficulty and to an increased risk of anastomotic leakage when the percentage of the pelvic cavity occupied by the tumor is high. Conclusion The percentages of the pelvic cavity occupied by the tumor and rectum are factors that influence surgical difficulty and the occurrence of complications and should be taken into consideration during the planning stages to ensure safe laparoscopic rectal cancer surgery.
The Clinical Outcomes Committee of the Japanese Society for Surgery of the Foot (JSSF) has conducted the second Field Survey of the Outcome Instrument for the Foot and Ankle version 2.
The survey of ...the Outcome Instrument version 2, which was composed of 43 items, was performed in 313 patients (154 men and 159 women) who had pathological conditions related to the foot and ankle. Optional sports items in the Outcome Instrument version 2 were analyzed in 123 patients. Internal consistency and construct validity of the Outcome Instrument version 2 were assessed. Correlation of the Outcome Instrument version 2 score with Short Form 36 (SF36) and JSSF scores was analyzed to evaluate criterion validity.
Both the EFA and CFA demonstrated good alignment of questionnaire items with their intended subscales in most cases. Sports items were not clearly classified into subgroups. Therefore, it seemed reasonable to use those as a set of questions in a single subscale. The present subscales, having similar names as the SF36 subscales, were closely correlated with the respective subscales. In those cases, the magnitude of the correlation coefficient was >0.6 (p < 0.001) except the present subscale called General Health and Well-being. Comparison of the present scores with JSSF evaluation scores showed satisfactory results except in patients with rheumatoid arthritis.
The Outcome Instrument version 2 demonstrated acceptable psychometric performances as outcome measures for patients with pathological conditions related to the foot and ankle. This outcome instrument would be helpful to evaluate patients with foot and/or ankle impairment. However, the analyses of the test-retest reliability and the influence of background factors such as age and gender, etc., on Outcome Instrument version 2 are needed in the third field survey.
The Clinical Outcomes Committee of the Japanese Society for Surgery of the Foot conducted a field survey using a novel foot and ankle outcome instrument. We report the development and evaluation of ...the Outcome Instrument version 1.
A total of 108 potential questions were extracted from literature published in the interval between 1990 and 2006. Tentative subscales proposed were "Degree of Foot Pain," "Foot Pain-related," "Physical Functioning and Daily Living," "Social Functioning" and "General Health and Well-being." After pre-testing in two different groups of patients, the Outcome Instrument version 1, which was composed of 46 items selected from the 108 questions, was administered to 256 patients (111 men and 145 women) with foot-and-ankle-related pathologic conditions and 243 healthy volunteers (125 men and 118 women). Cronbach's alpha coefficients were used for assessment of internal consistency of the instrument. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were utilized for evaluation of construct validity.
Neither a ceiling nor floor effect was observed in the responses from the patients. Significant differences were found in the responses to all of the questions between the patients and volunteers (P < 0.01 each). The Cronbach's alpha coefficients for each of the expected subscales indicated high reliability for most of the items and subscales. However, EFA extracted an additional subscale that should be interpreted as something related to shoe or shoe-fit. Further, both EFA and CFA indicated that "Degree of Foot Pain" and "Foot Pain-related" subscales were barely discernable with a factor correlation coefficient of 0.927.
The Committee partly revised the instrument, and the new subscales are as follows: "Foot Pain and Pain-related," "Physical Functioning and Daily Living," "Social Functioning," "General Health and Well-being" and "Shoe-related." Evaluation of the Outcome Instrument version 2 will be reported in the following paper.
Endocrine ductal carcinoma in situ (E‐DCIS) is an intraductal carcinoma characterized by endocrine features and expression of neuroendocrine markers. E‐DCIS and intraductal papilloma (IDP) resemble ...in their clinical features. However, the former is an intraductal carcinoma, and the latter is an intraductal benign lesion. It is sometimes difficult to distinguish E‐DCIS from IDP because both can show near solid intraductal cellular proliferation. Discrimination between lesions is important not only histopathologically, but also clinically. This study aimed to evaluate the applicability of CD56 and CD57 for the discrimination between E‐DCIS and IDP. Specimens were obtained from 17 E‐DCIS patients as the subject group, and 27 IDP patients as the control group, diagnosed in St Marianna University Hospital. E‐DCIS was diagnosed using Chromogranin A, Synaptophysin, and Grimelius stainings by the premise of histopathological features. These specimens were subjected to CD56, CD57 immunostainings. Staining results were compared between E‐DCIS and IDP. In our study, CD56 revealed significant differences for distinguishing E‐DCIS from IDP as determined by Fisher's test (cutoff: not less than 33–67%< immunopositivity, P < 0.05). We found that not only E‐DCIS but also IDP revealed immunopositivity for CD56. However, it is considered that E‐DCIS diagnosis is possible by diffuse immunopositivity of CD56 after having been based on histopathology.
Unfractionated heparin (UFH) is widely used in the treatment and prophylaxis of thrombosis. The anticoagulant effect of UFH is monitored according to activated partial thromboplastin time (APTT). ...However, there are reports of cases in which hemorrhagic complications develop despite APTT being maintained within the therapeutic range. This indicates there are problems with the monitoring method using APTT during UFH treatment. To assess the actual anticoagulant effect in UFH therapy using APTT as a monitoring method, we investigated changes in APTT and thrombin generation (TG) potential in vitro with the addition of UFH to samples from 10 healthy adults. There were large individual differences in the degree of APTT prolongation with the addition of UFH to samples from healthy adults. Furthermore, individual differences in the degree of TG change exceeded those in APTT in 7 subjects with comparable APTT changes caused by UFH (coefficients of variation: 2–5% for APTT, 10–50% for TG potential). Thus, with UFH treatment, there are large individual differences in the degree of TG inhibition even when APTT is within the appropriate range for coagulation control. These findings provide invaluable information for resolving the problem of hemorrhagic complications during UFH treatment based on the current APTT method.
Objective: An important cause of liver re-metastasis from colon cancer is remnant micrometastasis (MiM). MiM is a miniscule metastatic lesion that results from hematogenous spread of tumor cells ...along with or after the original metastasis from colon to liver. Thus, an adequate surgical margin is necessary to lower a patient’s risk of relapse. Questions have arisen whether the guideline 1-cm surgical margin can be reduced in cases in which neoadjuvant chemotherapy (NAC) has been performed. We conducted a histopathologic study to determine the appropriate hepatectomy margin in such cases. Methods: We studied 76 cases of colorectal liver metastasis treated between January 2005 and December 2013 at St. Marianna University School of Medicine Hospital. NAC had been performed in 35 of these cases. We evaluated patients’ sex; age; site, clinical stage, and histologic type of the primary tumor, clinical and histologic effects of the NAC, histologic characteristics and size of the hepatic macrometastasis, number of cases in which MiM was found and the number of MiMs per case, histologic characteristics and size of the MiM(s), distance from the macrometastasis to the MiM, and exact location of the MiM(s) and tested between-group differences in these variables statistically. We also tested correlation between size of the macrometastasis and both distance between the macrometastasis and MiM and the number of MiMs per case. Results: Positive, but non-significant, correlation was found between size of the macrometastasis and both distance between the macrometastasis and MiM and the number of MiMs per case. Regardless of whether NAC was performed, most MiMs we examined were within 5 mm of the macrometastasis, but some were within 9 mm. Conclusion: Our data indicate that, regardless of whether NAC is performed before hepatectomy for liver metastasis from colorectal cancer, a minimum 1-cm surgical margin is necessary to ensure inclusion of micrometastases.
We herein report on the current status of Japanese HIV-positive patients with coagulation disorders, primarily hemophilia, based on the national survey of 31 May 2006. The total number of registered ...patients was 1,431 (Hemophilia A 1,086; Hemophilia B 325; von Willebrand disease 8; others 12), and 604 of these patients were deceased by 31 May 2006. The survival rate after the beginning of 1983 was evaluated by the Kaplan–Meier method. The total number of surviving patients was 827, and the survival rate on 31 May 2006 was 55.7 ± 1.4%. Among the 827 surviving patients, HCV antibody was observed in 740, was negative in 16, and was not reported in 71 patients. Thus, the prevalence of HCV infection was 98% in the surviving patients based on the presence of HCV antibody. Among the 604 deceased patients, liver disease was reported as a cause of death in 149 cases (25%), and infection with HCV was reported as the possible cause of liver disease in 120 cases (20%). After 1997, 63 cases among the subtotal of 148 deaths had critical hepatic disease that originated from HCV infection, which accounted for 43% of the subtotal. The cumulative rate of patients who received interferon therapy was 32%. Interferon therapy should be prescribed more frequently to HIV-positive patients with coagulation disorders in order to realize the survival benefits, although clinicians should be aware of side effects and toxicities.
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