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Background: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). Methods: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. Results: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. Conclusion: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy. In this retrospective cohort study involving 3154 patients, a strong correlation between recurrence-free and overall survival was established, and this correlation was more pronounced in patients who had a more effective response to neoadjuvant chemotherapy. These findings are beneficial for expediting the development of novel neoadjuvant treatments by shortening the duration of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability.Methods: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists.Results: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5).Conclusions: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN.Trial Registration: The UMIN Clinical Trials Registry Identification Number: 000004218. [ABSTRACT FROM AUTHOR]

Objectives: Photodynamic therapy (PDT) is an effective salvage endoscopic treatment for local failure at the primary site after chemoradiotherapy (CRT) in esophageal cancer patients. However, the contribution of local control by salvage PDT to the prognosis is unclear. We investigated whether complete response at primary site by salvage PDT could improve the prognosis. Methods: Between January 2008 and March 2016, 34 patients received salvage PDT for local failure of esophageal cancer limited to stage T1–2 after definitive CRT or radiotherapy. Local complete response (L‐CR) rate, adverse events, overall survival (OS), and progression‐free survival (PFS) were assessed retrospectively. Results: Local complete response rates after PDT were 68% (23/34; 95% CI, 50–83%) in all patients: 81% (17/21; 95% CI, 58–95%) for stage T1 and 46% (6/13; 95% CI, 19–75%) for stage T2 patients. Grade 3 esophageal stricture occurred in one patient. The median follow‐up was 26.0 months (range, 3.7–93.6 months); 21 patients died. The median survival times were 54.3 months in patients who achieved L‐CR after PDT (L‐CR group) and 19.8 months in those who did not (non‐CR group). The 2‐year OS rates were 79% (95% CI, 54–92%) in the L‐CR group and 40% (95% CI, 11–68%) in the non‐CR group (P = 0.0389; log‐rank test). The median PFS was 21.2 months in the L‐CR group and 1.9 months in the non‐CR group (P < 0.001; log‐rank test). Conclusion: Achieving L‐CR by salvage PDT for local failure after CRT in esophageal cancer was associated with good prognosis. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P  = 0.017 for A vs. C, P  = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P  = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P  < 0.0001 for trend). LVL grade C was a strong predictor of mSPM other than esophagus (RR = 3.41 for A vs. C). LVL grade may be a useful predictor of the risk of mSPM other than esophagus after ER in patients with early esophageal SCC. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles.Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated.Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2-NMRAL2P-NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors.Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC. [ABSTRACT FROM AUTHOR]

Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin’s lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the long-term clinical outcome of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT) for cervical esophageal squamous cell carcinoma (CESCC).Methods: We retrospectively reviewed the medical records of 30 patients with CESCC [clinical stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty-six patients underwent elective nodal irradiation for the neck node levels III, IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy. Twenty-six patients underwent concurrent chemotherapy. Initial disease progression sites, locoregional control (LRC) rate, overall survival (OS) rate, and toxicities were retrospectively evaluated. A univariate analysis was performed to identify prognostic factors.Results: With a median follow-up of 110 months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5- and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant and both area accounted for 83%, 6% and 11% of the initial progression sites. Unresectable status and M1LYM were significantly associated with poor LRC (p < 0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in 13.3% of patients. During the follow-up, patients without any disease progression did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events, including hypothyroidism and cardiovascular disease, were observed; 5- and 10-year cumulative incidence rates of grade 2 hypothyroidism and ≥grade 3 cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively.Conclusions: Definitive radiotherapy yields a cure for patients with CESCC while preserving their laryngopharyngeal function. The poor LRC rate in the advanced stage needs to be overcome for a better prognosis. As the incidence of radiation-induced hypothyroidism and cardiovascular disease was not low, long-term survivors should be followed up for these symptoms. [ABSTRACT FROM AUTHOR]

Objectives. Superficial-type pharyngeal squamous cell carcinoma (STPSCC) is defined as carcinoma in situ or microinvasive squamous cell carcinoma without invasion to the muscular layer. An exploration of the biological characteristics of STPSCC could uncover the invasion mechanism of this carcinoma. Phosphatidylcholine (PC) in combination with fatty acids is considered to play an important role in cell motility. Imaging mass spectrometry (IMS) is especially suitable for phospholipid analysis because this technique can distinguish even fatty acid compositions. Study Design. IMS analysis of frozen human specimens. Methods. IMS analysis was conducted to elucidate the distribution of PC species in STPSCC tissues. STPSCC tissue sections from five patients were analyzed, and we identified the signals that showed significant increases in the subepithelial invasive region relative to the superficial region. Results. Three kinds of PC species containing arachidonic acid, that is, PC (16:0/20:4), PC (18:1/20:4), and PC (18:0/20:4), were increased in the subepithelial invasive region. Conclusion. These results may be associated with the invasion mechanism of hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The survival benefit of chemotherapy (CTx) compared with best supportive care (BSC) is unclear in patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M-ESCC) previously treated with fluorouracil (FU), platinum (PT), and taxane (TAX).Patients and Methods: The data of 283 consecutive patients with R/M-ESCC, who could not tolerate or whose tumor was refractory to all three agents (FU, PT, and TAX) between March 2003 and November 2014, were retrospectively reviewed. Patient selection criteria were as follows: age 20-75 years, performance status 0-2, and preserved organ function. Prognostic factors for overall survival (OS), defined as survival time from the last administration of all three agents, were analyzed using the Kaplan-Meier method and Cox proportional hazards model.Results: Of the 283 patients, 147 received BSC and 136 received CTx (PT-containing regimen 37, investigative new drugs 28, irinotecan-containing regimen 29, TAX alone 25, FU alone 16, others 4). Most patients' tumors were refractory to all three agents. The median OS of BSC and CTx patients was 4.2 and 7.8 months (hazard ratio 0.41; 95% confidence interval 0.31-0.54), respectively. Multivariate analysis with or without propensity score matching indicated that BSC, metastatic sites other than lung, liver, or bone, and hemoglobin <10 g/dL were associated with poor prognosis.Conclusion: CTx might provide a survival benefit over BSC even for patients with R/M-ESCC who cannot tolerate or whose tumor is refractory to all three agents. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Narrow band imaging (NBI) combined with magnifying endoscopy enables us to detect superficial laryngo-pharyngeal cancers, which are difficult to detect by standard endoscopy. Endoscopic laryngo-pharyngeal surgery (ELPS) is a technique developed to treat such lesions and the purpose of this study is to evaluate the usefulness of ELPS for superficial laryngo-pharyngeal cancer.Patients and Methods: Seventy five consecutive patients with 104 fresh superficial laryngo-pharyngeal cancers are included in this study. Under general anesthesia, a specially-designed curved laryngoscope was inserted to create a working space in the pharyngeal lumen. A magnifying endoscope was inserted transorally to visualize the field and a head & neck surgeon dissected the lesion using the combination of the orally-inserted curved grasping forceps and electrosurgical needle knife in both hands. The safely, functional outcomes, and oncologic outcomes of ELPS were evaluated retrospectively.Results: Median operation time per lesion was 35 min. Post-operative bleeding occurred in 3 cases and temporal subcutaneous emphysema occurred in 10 cases. No vocal fold impairment occurred after surgery. The median fasting period was 2 days and all patients except one have a normal diet with no limitations. Local recurrence occurred in 1 case, and the 3-year overall survival rate and the 3-year disease specific survival rate was 90% and 100%, respectively.Conclusions: ELPS is a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, and enjoys the merit of both procedures. ELPS makes it possible to perform minimally-invasive surgery, preserving both the swallowing and phonation functions. [ABSTRACT FROM AUTHOR]

Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre- and post-treatment biopsy specimens of 30 ESCC patients and 121 pre-treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-activation associated genes such as IFNG, PRF1, and GZMB, were found in post-treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-activated cases, designating them as I-type, from other cases. However, despite the better CR rate in the I-type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-type was significantly better than that of the CDH2-positive cases in the I-type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested to cooperatively enhance the effect of CRT in the CDH2-negative I-type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC. [ABSTRACT FROM AUTHOR]

In esophageal squamous cell carcinoma, the depth of invasion into the wall is closely associated with metastasis to lymph nodes. Esophageal cancer invading the muscularis mucosae could be curably treated by endoscopic submucosal dissection but cancer with submucosal invasion necessitates surgical resection and/or chemoradiotherapy. Therefore, pretreatment diagnosis of invasion depth is crucially important for selecting appropriate treatment strategies for each individual patient. To estimate the depth of cancer invasion for early squamous cell carcinoma of the esophagus, standard endoscopy with image enhancement and endoscopic ultrasound are currently considered the best methods. [ABSTRACT FROM AUTHOR]

Fujii S, Yamazaki M, Muto M & Ochiai A (2010) Histopathology 56, 510–522 Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinoma Aims: Superficial squamous epithelial lesions of the pharynx are increasingly recognized by architectural changes in the intraepithelial papillary capillary loop (IPCL) assessed by narrow-band imaging (NBI). The aim was to explore the histology of squamous epithelial precursor lesions and superficial-type pharyngeal squamous cell carcinoma (STPSCC), including squamous cell carcinoma (SCC) in situ and early invasive SCC, by focusing on microvascular irregularities to investigate the composition of those lesions and to explore the pathological characteristics of STPSCCs. Methods and results: Several pathological factors including thickness of intraepithelial squamous cell carcinoma (IESCC) and tumour thickness and microvascular density (MVD) were examined in 104 STPSCCs from 69 patients. The results show that architectural change of IPCL was recognized in precursor lesions in parallel with architectural disturbance and cytological atypia for criteria of diagnosing dysplasia. In 104 STPSCCs, the MVD of IESCC was correlated with the thickness of IESCC ( P = 0.0115). Moreover, invasive SCC showed significantly higher MVD of IESCC ( P = 0.0078) and there was significant correlation between the thickness of IESCC and subepithelial invasion ( P < 0.0001). Conclusions: Microvascular irregularities are an important pathological factor in carcinogenesis and early invasiveness of SCC of the pharynx. [ABSTRACT FROM AUTHOR]

Background The newly developed narrowband imaging (NBI) gastrointestinal endoscope makes possible the detection of superficial carcinoma in the oropharynx and hypopharynx, which is difficult with the conventional laryngoscope. Here, we investigated whether the combined use of laryngoscope with NBI allows the detection of superficial carcinoma in this region. Methods A total of 51 superficial, histologically confirmed lesions in 29 patients were studied. The quality of visualization of superficial carcinoma in the oropharynx and hypopharynx using the NBI-equipped laryngoscope was evaluated in comparison with the results by conventional laryngoscopy. Results The NBI laryngoscope provided better detection of the irregular microvascular pattern of carcinoma than the conventional laryngoscope (p <.05) and better visualization of the demarcation line (p <.05), and thus significantly better visualization of the lesions. Conclusion The NBI laryngoscope may play an important role in the diagnosis and treatment of superficial carcinoma in the oropharynx and hypopharynx. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Background The 7th edition of the Union for International Cancer Control (UICC) TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. In the 8th edition of UICC-TNM staging system, there is no information available for treatment modality (surgery alone or neoadjuvant therapy [NAC] followed by surgery [NAC-S]), although clinical stage, neoadjuvant pathologic stage, and pathologic stage were analyzed and identified. The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal squamous cell cancer (ESCC) patients treated by NAC-S. Methods Database of 140 consecutive ESCC patients in our hospital was retrospectively restaged in 7th and 8th UICC-TNM system. The prognostic impacts of pathologic stage after NAC according to the both staging systems were compared. Results The median follow-up period was 4.8 years (range 0.2–9.7), with 49 patients dead at the time of analysis. In 7th edition, the 3-year overall survival rates (3y-OS) of ypStages 0, I, II, III, and IV were 100%, 93.5%, 93.5%, 43.9%, and 0.0%, respectively. In 8th edition, the 3y-OS of ypStages 0, I, II, III, and IV were 100%, 96.5%, 90.2%, 51.7%, and 29.6%, respectively. There were no marked differences between 7th and 8th edition in the prognoses. The both editions poorly distinguish the prognoses of ypStages 0, I, and II. For pathological prognostic group in 7th edition, the 3y-OS of Groups 0, I, II, III, and IV were 100%, 97.0%, 90.6%, 43.9%, and 0.0%, respectively. For pathological prognostic group in 8th edition, the 3y-OS of Groups 0, I, II, III, and IV were 100%, 96.7%, 89.8%, 51.7%, and 29.6%, respectively. For patients with ypStages 0-II, pretreatment higher CEA was poor prognostic factor (HR 7.1, 95% confidence interval 1.9–25.9). Conclusion Our study indicates the problem that the ypStage in the 8th TNM staging system poorly distinguish the prognoses of ypStages 0, I, and II in patients undergoing NAC-S. Additional study is needed to evaluate the role of ypStage 0-II incorporation of new prognostic factors. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) is an effective salvage treatment for local failure after chemoradiotherapy in patients with esophageal cancers. However, the treatment strategy for local failure after initial PDT has not been established, and the safety and efficacy of repetitive PDT for such lesions are also unknown. Methods We retrospectively investigated 33 esophageal cancer patients who received initial salvage PDT at Kyoto University Hospital between May 2012 and November 2017. Additionally, we examined the treatment outcomes of those patients who received repetitive PDT. Results Twenty-one patients (64%) achieved local complete response (CR) by initial PDT, and local recurrence did not occur in those patients. Eleven patients (33%) had residual lesions after initial PDT. Among these, 7 patients were treated with repetitive PDT, 2 patients selected best supportive care, 1 patient was treated with surgery, and 1 patient was treated with chemotherapy. Five of the 7 patients who received repetitive PDT were treated with talaporfin sodium, and 2 patients were treated with porfimer sodium. The median age of the patients who received repetitive PDT was 70 years old, and all patients were men. Regarding histology, 6 patients were squamous cell carcinoma and 1 patient was adenocarcinoma. The median period from initial PDT to repetitive PDT was 3 months (range 1–4). Lesion depth before initial PDT was T1 in 3 patients and T2 in 4 patients. Lesion depth before repetitive PDT was T1 in 5 patients, and T2 in 2 patients. Local CR rate in 7 patients treated with repetitive PDT was 42.9% (3/7). Additionally, local CR rate in T1 cases was 60% and 0% in T2 cases. Adverse events of grade 3 or higher were not observed in any patient. Conclusion Repetitive salvage PDT was considered to be an effective and safe treatment option in residual T1 lesions after initial PDT for local failure of esophageal cancer treated with chemoradiotherapy. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N2-ethylidene-2′-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N2-ethylidene-2′-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N2-ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. [ABSTRACT FROM AUTHOR]

Optical technological innovations enable us to visualize cellular nuclei endoscopically. Herein is described a protocol design for a multicenter study for the ex vivo evaluation of endocytoscopy. The present study was performed by the Endoscopy Forum Japan study group. [ABSTRACT FROM AUTHOR]

In the multistep process of squamous epithelial carcinogenesis, squamous epithelial dysplasia has been considered to be a preinvasive stage of squamous cell carcinoma. If we could distinguish a dysplasia at high risk, such lesions could be targets for local treatment such as endoscopic mucosal resection to avoid the transformation to invasive carcinoma. Narrow-band imaging, a new optical technology, is useful to identify the cancerous lesion compared to conventional white light image. In addition, narrow-band imaging combined with magnifying endoscopy makes it possible to visualize the changes of microvascular architecture occurring in the epithelium. To evaluate whether these endoscopic findings are reliable to diagnose a dysplasia at high risk, a prospective study on the basis of the standards for reporting diagnostic accuracy initiative is needed. If endoscopic assessment of intraepithelial squamous neoplasia is reliable, it would be of benefit to the patients’ outcome and improve cost effectiveness of care because of the avoidance of developing invasive carcinoma and the reduction of unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cervical nodal metastasis from clinically undetectable primary squamous cell carcinoma (SCC) accounts for 1–2% of head and neck malignancies. We retrospectively evaluate the ability of Narrow band imaging combined with magnifying endoscopy (NBI-ME) to detect the primary sites of superficial SCC in the head and neck region. Methods: This was a report of 11 patients. We performed with NBI-ME to detect unknown primary sites in the head and neck. Results: Among 11 patients, primary sites were detected in eight. Primary sites were detected in the head and neck in 6 (54.5%) of 11 patients on NBI-ME, all 6 primary lesions were a flat lesion. Two patients in whom primary lesions could not be detected on NBI-ME, one had submucosal tumor like lesion, the other featured by a detectable primary lesion 19months after neck dissection. Conclusion: NBI-ME can be recommended as an essential procedure for the detection of primary lesions in patients with primary unknown cervical lymph node metastasis. [Copyright &y& Elsevier]

Abstract: Background and purpose: There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Materials and methods: Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60Gy in 30 fractions. Up to 40Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. Results: One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0–5.3%) patient experienced elective nodal failure without any other site of recurrence. Conclusion: In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed. [Copyright &y& Elsevier]

: PurposeTo compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus and to identify useful clinicopathologic and biologic markers to select better treatment.: Methods and materialsBetween August 1992 and April 1999, 98 consecutive patients were selected for this study; 53 were treated with chemoradiotherapy and 45 with surgery. The patients in the chemoradiotherapy group received 5-fluorouracil combined with cisplatin plus 60 Gy of radiation, and those in the surgery group received an esophagectomy with radical node dissection. Biologic markers were investigated immunohistochemically using pretreatment biopsy specimens.: ResultsThe baseline clinical TNM stage was more advanced in the chemoradiotherapy group than in the surgery group. With a median follow-up period of 43 months, the 5-year survival rate was 46% in the chemoradiotherapy and 51% in the surgery group, without statistical significance (p = 0.47, log–rank test). Cox regression analysis for prognosis revealed that epidermal growth factor receptor positivity, high microvessel density, and cyclin D1 positivity yielded a low value for relative risk (0.66, 0.54, and 0.62, respectively), which favored chemoradiotherapy over surgery, without statistical significance.: ConclusionThis nonrandomized study showed a trend for the chemoradiotherapy in the treatment of esophageal carcinoma, but the results need to be confirmed by additional study. [Copyright &y& Elsevier]