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Positive proximal resection margins are strongly associated with anastomotic recurrence in esophageal cancer. However, the prognostic significance of dysplastic proximal resection margins remains unclear. The aim of this study is to investigate whether the dysplastic proximal resection margin can predict anastomotic recurrence and overall survival in patients with esophageal squamous cell carcinoma. Between 2000 and 2014, patients with esophageal squamous cell carcinoma who received a nonpalliative resection and survived the perioperative period were included. Two expert pathologists independently reviewed the proximal resection margin status, which was classified as negative, dysplastic, or positive. The kappa statistic was used to test interobserver reliability. Anastomotic recurrence and overall survival served as the main outcome measures. The study cohort consisted of 469 patients (445 males and 27 females). There was an excellent interobserver agreement for negative (kappa = 0.88), dysplastic (kappa = 0.88), and positive (kappa = 1) proximal resection margins-which were identified in 418 (89.1%), 37 (7.9%), and 14 (3.0%) patients, respectively. After a median follow-up of 21.6 months, 30 (6.4%) patients developed an anastomotic recurrence. Compared with patients with negative proximal resection margins (24/418, 5.7%), the occurrence of anastomotic recurrence was more commonly observed in those with positive proximal resection margins (3/14, 21.4%, P = 0.017) but not in those with dysplastic proximal resection margins (3/37, 8.1%, P = 0.56). Multivariable Cox regression analysis identified positive proximal resection margins (hazard ratio: 5.93, P = 0.010) and advanced clinical stage (hazard ratio: 12.04, P = 0.023) as independent risk factors for anastomotic recurrence. Dysplastic proximal resection margins were not retained in the model as an independent predictor (hazard ratio: 1.38, P = 0.602). The 5-year overall survival rates of patients with negative (38.2%) and dysplastic margins (27.0%) were similar (P = 0.814), and significantly higher than that observed in those with positive proximal resection margins (9.5%, P = 0.015). In conclusion, dysplastic proximal resection margins can be identified in at least 7.9% of patients with esophageal squamous cell carcinoma, but neither they are associated with an increased risk of anastomotic recurrence nor they portend a poor overall survival., (© The Author(s) 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Baculovirus (BV) holds promise as a vector for anticancer gene delivery to combat the most common liver cancer-hepatocellular carcinoma (HCC). However, in vivo BV administration inevitably results in BV entry into non-HCC normal cells, leaky anticancer gene expression and possible toxicity. To improve the safety, we employed synthetic biology to engineer BV for transgene expression regulation. We first uncovered that miR-196a and miR-126 are exclusively expressed in HCC and normal cells, respectively, which allowed us to engineer a sensor based on distinct miRNA expression signature. We next assembled a synthetic switch by coupling the miRNA sensor and RNA binding protein L7Ae for translational repression, and incorporated the entire device into a single BV. The recombinant BV efficiently entered HCC and normal cells and enabled cis-acting transgene expression control, by turning OFF transgene expression in normal cells while switching ON transgene expression in HCC cells. Using pro-apoptotic hBax as the transgene, the switch-based BV selectively killed HCC cells in separate culture and mixed culture of HCC and normal cells. These data demonstrate the potential of synthetic switch-based BV to distinguish HCC and non-HCC normal cells for selective transgene expression control and killing of HCC cells.

Objectives: Recent advances in neoadjuvant chemoradiotherapy (nCRT) have significantly increased the rates of pathological complete response achieved by patients with oesophageal cancer. Consequently, a watchful waiting strategy based on 'active endoscopic surveillance and surgery as needed' has been proposed for cases without clinical evidence of disease after neoadjuvant chemoradiotherapy. Here, we investigated whether endoscopic surveillance is a reliable tool for the detection of the initially unidentified residual cancer in this patient group., Methods: We performed a careful pathological re-review of all cases with oesophageal squamous cell carcinoma, who attained a clinical complete response, despite showing a pathological non-complete response. The detailed anatomical locations of such unidentified malignancies were investigated in each patient to determine the prevalence of cancer involvement for each oesophageal layer., Results: Among the 73 patients with clinical complete response, 46 (63%) patients were found to have pathological non-complete response. The majority (89.1%; n = 41) of patients had evidence of residual cancer in the oesophagus, whereas only 5 (10.9%) patients had T0N+ disease. However, a high percentage (39.1%; n = 16) of patients had no detectable cancer in the mucosa and 9 of them also had no detectable cancer in sub-mucosal layer, ultimately hampering their detection via endoscopic biopsy., Conclusions: Nearly 40% of patients with oesophageal squamous cell carcinoma who attained clinical complete response but showed a pathological non-complete response had residual cancer hidden underneath a cancer-free mucosa layer., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: A 'surgery as needed' strategy has been proposed for patients with oesophageal cancer who truly achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT). However, the ability to detect residual disease remains problematic. This study investigated the anatomical locations and pathological characteristics of residual cancer in patients with oesophageal squamous cell carcinoma (SCC) who achieved a near pCR following nCRT., Methods: Patients with oesophageal SCC who achieved a near pCR after nCRT were eligible. Near pCR was defined as residual cancer in the resection specimen representing less than 10 per cent of the apparent original tumour area., Results: Detailed histopathological reassessment of 76 consecutive patients (mean age 54·4 years) with a near pCR was undertaken. Some 32 patients (42 per cent) with a near pCR had no detectable mucosal lesions. Residual tumour was identified most frequently in the submucosal layer (54, 71 per cent), followed by the mucosa (44, 58 per cent), muscle layer (36, 47 per cent) and adventitia (22, 29 per cent) (P < 0·001). Among patients without ypT1a disease, increasing depth of tumour invasion correlated negatively with the likelihood of mucosal involvement. Of patients with ypT3 disease, 16 of 22 had no detectable cancer located in the mucosa, compared with six of 29 with ypT1b disease (P < 0·001)., Conclusion: Better tools for predicting pCR are required before considering a 'surgery as needed' approach in the management of oesophageal cancer., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients., (© 2015 International Society for Diseases of the Esophagus.)

Fresh frozen plasma (FFP) transfusion remains a significant issue for blood banks because of a lack of consensus regarding its appropriate use. To study the factors influencing physician compliance, we evaluated FFP transfusion episodes in the year 2008, using a computerized transfusion decision support system. A total of 10,926 episodes were reviewed. The demographic data, physician compliance, and therapeutic efficacy were investigated. The physician noncompliance rate was 46.5%. The highest number was ordered by the hepatobiliary division, which might be due to the high incidence of liver cirrhosis and hepatoma in Taiwan. Excluding the cases for plasma exchange and emergency surgery, 31.2% of episodes had abnormal coagulation results before transfusions. The therapeutic efficacy is statistically significant in patients with abnormal pretransfusion coagulation tests (P < .001). Computerization may be a favorable trend in medical management systems, but it should be more functional to improve medical quality.

AA3 is a novel antibody raised against human amnion, which reacts with the basement membrane of various epithelia of ectodermal origin. We used AA3 to examine the epidermal basement membrane zone in normal skin and different genetically determined types of epidermolysis bullosa (EB), by indirect immunofluorescence. AA3 staining was normal in dystrophic and simplex EB, but was markedly reduced in lesional and non-blistered skin in severe forms of junctional EB. In non-lethal junctional EB, the intensity of staining was variable and appeared to be inversely associated with disease severity, but did not correlate with demonstrable abnormalities of hemidesmosomes. AA3 binding was not reduced in pemphigoid lesions or normal suction blisters. It appeared to localize to the lamina lucida, but with different characteristics compared with antibodies to laminin and bullous pemphigoid antigen. These finding suggest that AA3 recognizes an antigen (or antigens) which may be involved in a primary biochemical defect in junctional EB. Moreover, this antibody may act as a new probe for this potentially lethal mechano-bullous disease.

Sera from five patients with clinically and immunopathologically proven herpes gestationis were studied by complement fixing immunofluorescence and complement fixing immuno-electron microscopy using specimens of skin, amniochorion and placenta. The results demonstrated that the complement fixation antibody (herpes gestationis factor) could bind to the basement membrane zone of skin, amnion and chorion laeve but not to that of the placental syncytiotrophoblast. These data suggest that the herpes gestationis factor may be induced by the basement membrane zone antigens of extra-villous cytotrophoblasts.