Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. CONCLUSION: Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. METHODS: Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. RESULTS: Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p < 0.001 and p = 0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p = 0.04 and p < 0.001, respectively), but only the regression index predicted NACRT efficacy (p = 0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p < 0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p = 0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp 2.086, p = 0.043). CONCLUSION: The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.

Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma.

L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.

Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

Anatomical versus non-anatomical resection for hepatocellular carcinoma.

BACKGROUND: The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis following anatomical versus non-anatomical hepatic resection for hepatocellular carcinoma (HCC). METHODS: Consecutive patients with HCC without macroscopic vascular invasion, treated by curative resection between 1981 and 2012 at Osaka Medical Centre, were included in this retrospective study. The outcomes of patients selected by propensity score matching were compared. RESULTS: Some 1102 patients were included, 577 in the anatomical and 525 in the non-anatomical resection group. By propensity score matching, 329 patients were selected into each group. Demographic, preoperative and tumour variables were similar between the propensity score-matched groups, including tumour size, tumour multiplicity, α-fetoprotein level and 15-min indocyanine green retention rate at 15 min. The incidence of microvascular invasion was higher in the matched anatomical resection group (P = 0·048). Stratified analysis of recurrence-free and overall survival rates revealed no statistically significant differences between the two propensity score-matched groups (P = 0·704 and P = 0·381 respectively). There was also no significant difference in the early recurrence rate within 2 years after resection between these groups (P = 0·726). Subset analysis of the early recurrence-free survival rate in patients with and without microvascular invasion revealed no significant differences between the groups (P = 0·312 and P = 0·479 respectively). CONCLUSION: The resection method had no impact on the risk of HCC recurrence or survival.

Plasmodium berghei infection ameliorates atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Atopic diseases are more prevalent in industrialized countries than in developing countries. In addition, significant differences in the prevalence of allergic diseases are observed between rural and urban areas within the same country. This difference in prevalence has been attributed to what is called the 'hygiene hypothesis'. Although parasitic infections are known to protect against allergic reactions, the mechanism is still unknown. The aim of this study was to investigate whether or not malarial infections can inhibit atopic dermatitis (AD)-like skin lesions in a mouse model of AD. METHODS: We used NC/Nga mice which are a model for AD. The NC/Nga mice were intraperitoneally infected with 1 × 10(5) Plasmoduim berghei (Pb) XAT-infected erythrocytes. RESULTS: Malarial infections ameliorated AD-like skin lesions in the NC/Nga mice. This improvement was blocked by the administration of anti-asialo GM1 antibodies, which are anti-natural killer (NK) cells. Additionally, adoptive transfer of NK cells markedly improved AD-like skin lesions in conventional NC/Nga mice; these suggest that the novel protective mechanism associated with malaria parasitic infections is at least, in part, dependent on NK cells. CONCLUSIONS: We have experimentally demonstrated for the first time that malarial infections ameliorated AD-like skin lesions in a mouse model of AD. Our study could explain in part the mechanism of the 'hygiene hypothesis', which states that parasitic infections can inhibit the development of allergic diseases.

Detection of human papillomavirus (HPV) in patients with squamous cell carcinoma and the clinical characteristics of HPV-positive cases.

BACKGROUND: The association between human papillomavirus (HPV) and squamous cell carcinoma (SCC) has been reported; however, the prevalence of HPV infection varies, and the clinical characteristics of HPV-positive cases remain unknown. OBJECTIVES: To elucidate the frequency of HPV infection in a series of Japanese patients with SCC and to identify the characteristics of HPV-positive cases. METHODS: We evaluated 38 patients with SCC treated at our department. HPV typing was performed using SCC samples from different body sites. Immunohistochemical staining for HPV proteins and p16(INK) (4a) was performed, in addition to polymerase chain reaction and in situ hybridization. The clinical characteristics of the HPV-positive cases were clarified. RESULTS: Two genital lesions were positive for HPV type 16. Both cases showed basaloid features histopathologically, and were considered to have SCC that had arisen from bowenoid papulosis. p16(INK) (4a) expression was observed in 11 cases, including the two HPV-positive cases. CONCLUSIONS: The present study indicates that the prevalence of HPV is not high and that bowenoid papulosis is an HPV-associated precancerous lesion. Further investigation is necessary to assess the relationship between HPV infection and SCC.

Human papillomavirus type 56-associated Bowen disease.

BACKGROUND: Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. OBJECTIVE: To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. METHODS: Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. RESULTS: Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. CONCLUSIONS: This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.

The significance of abdominal para-aortic lymph node metastasis in patients with lower thoracic esophageal cancer.

Para-aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.

Prevention of gastroduodenal content reflux and delayed gastric emptying after esophagectomy: gastric tube reconstruction with duodenal diversion plus Roux-en-Y anastomosis.

Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial.

Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity.

The identification of molecular markers useful for predicting prognosis in pancreatic cancer patients is crucial for advances in disease management. The epithelial cell adhesion molecule (Ep-CAM) is known to express in most epithelial malignancies and was reported as a tumor marker or a candidate of molecular targeting therapy. However, the clinical significance of Ep-CAM expression in pancreatic cancer is not well-known. We determined the difference of malignant potential between parental and Ep-CAM-transfected pancreatic cancer cell lines by using proliferation, invasion and migration assay. Furthermore, we determined the relationship between tumoral Ep-CAM expression of resected specimens and clinical prognosis in 95 pancreatic cancer patients receiving radical surgery at two different cancer centers. One of the three Ep-CAM-transfected cell lines showed significantly low proliferation rate compared with the parental cell, while there was no difference in the other two cell lines. In invasion and migration assays, Ep-CAM-transfected cells showed significantly lower malignant potential than parental in all of the three cell lines. In 95 pancreatic cancer patients, 47 patients showed high-Ep-CAM expression, while 48 patients showed low, and there was no difference of clinicopathological features between Ep-CAM high and low-expression group. High-Ep-CAM expression group showed significantly good prognosis in overall survival (3-year survival; 56.2 versus 19.2%, P=0.0018) as well as in disease-free survival (3-year survival; 40.3 versus 14.4%, P=0.038) compared with low-expression group. In addition, the impact of Ep-CAM was observed strongly in LN-negative group when the influence of Ep-CAM was examined with dividing patients into LN-positive and negative group. In multivariate analysis, Ep-CAM expression was one of the independent prognostic factors as well as histology and lymph node metastasis. Ep-CAM expression was found to be related to the suppression of pancreatic cancer cell activity and the good prognosis in pancreatic cancer patients receiving the curative resection.

Lupus cystitis: a case report and review of the literature.

Lupus cystitis is a rare complication associated with systemic lupus erythematosus (SLE). This rare disorder has been reported mainly from East Asia, especially from Japan. In this study, we describe a patient with lupus cystitis and review 37 reported cases in Japan. Bowel symptoms preceded urinary symptoms in 13 of 37 (35%) patients, whereas five patients complained of only bowel symptoms. Hydronephrosis was detected in 34 of 37 patients (92%). The possibility of lupus cystitis should be considered when patients complain of bowel or urinary symptoms. Examination for hydronephrosis is critical for diagnosis.

Persistent urticaria characterized by recurrent lasting urticarial erythema with histological features of prominent perivascular eosinophilic infiltration.

We report a 29-year-old woman with a 15-year history of recurrent pruritic urticarial erythemas. The individual lesions lasted for > 24 h, and antihistaminic agents were not effective. Histological examination of a skin biopsy revealed interstitial oedema of the dermis and perivascular infiltration of numerous eosinophils without vasculitis. No internal organ involvement or peripheral blood eosinophilia was present. A diagnosis of persistent urticaria was made and the patient was successfully treated with oral corticosteroid therapy. Persistent urticaria has been described as an unusual reaction that lasts longer than typical urticaria. It is effectively treated with corticosteroids, but not with antihistaminic agents. In order to choose the most effective treatment, persistent urticaria should be recognized as a different clinical condition from typical urticaria.

A possible inhibitory action of diaminodiphenyl sulfone on tumour necrosis factor-alpha production from activated mononuclear cells on cutaneous lupus erythematosus.

BACKGROUND: We have previously reported that diaminodiphenyl sulfone (DDS; dapsone) can bring about significant clinical improvement in patients with cutaneous lupus erythematosus (CLE). However, the pharmacological actions of DDS in the skin lesion of patients with CLE are still unknown. OBJECTIVE: In this study, we aimed to clarify the pharmacological actions of DDS on CLE. METHODS: We conducted an in vitro study to examine the effects of DDS on the mRNA expression and production of cytokines on lipopolysaccharide-stimulated peripheral blood mononuclear cells. Results. DDS suppressed mRNA expression of tumour necrosis factor (TNF)-alpha and significantly decreased the level of TNF-alpha in culture supernatant. CONCLUSIONS: DDS may exert an anti-inflammatory action by suppressing TNF-alpha produced by activated mononuclear cells.