WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial

Objective

The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity.

Methods

A phase II clinical trial was conducted during the period of 2004–2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient’s condition became significantly worse due to the disease progression.

Results

Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04–7.19, p = 0.043).

Conclusion

WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.     

High Expression of Calcitonin Gene-Related Peptide and Substance P in Esophageal Mucosa of Patients with Non-Erosive Reflux Disease

Background

Visceral hypersensitivity is an important etiology of non-erosive reflux disease (NERD). Calcitonin gene-related peptide (CGRP) and substance P (SP) are involved in the sensitization of afferent neuronal pathways.

Aim

The objectives of this study were to evaluate visceral hypersensitivity in NERD patients, investigate the association between visceral hypersensitivity and mucosal expression of SP and CGRP, and assess their involvement in the pathogenesis of NERD.

Methods

Twenty-six NERD patients and 12 healthy volunteers were recruited. Intraesophageal balloon distention was performed, and initial perception threshold (IPT) and threshold of discomfort (ToD) were determined. Immunohistochemical staining was used to measure the optical density (OD) of CGRP and SP-reactive levels in esophageal mucosa, and the numbers of CGRP and SP-reactive neural fibers.

Results

IPT and ToD were 9.6 ± 4.8 and 12.3 ± 3.2 ml, respectively, in NERD patients, significantly lower than for controls (13.2 ± 7.5 and 21.6 ± 5.7 ml, P < 0.05 and P < 0.01, respectively). Mean OD values for CGRP and SP staining were significantly higher in NERD than for controls (both P < 0.05) and, in NERD, were negatively correlated with IPT and ToD (all P < 0.01). Numbers of CGRP and SP-reactive neural fibers in esophageal submucosa of NERD patients were significantly increased (both P < 0.05).

Conclusions

Expression of esophageal epithelial CGRP and SP is increased, and correlates negatively with perception thresholds in NERD. These findings may aid understanding of peripheral visceral hypersensitivity and the development of new therapeutic approaches for management of NERD.     

Salivary Bicarbonate as a Major Factor in the Prevention of Upper Esophageal Mucosal Injury in Gastroesophageal Reflux Disease

Background

It has been previously demonstrated that the exposure of the lower esophageal mucosa to acid and pepsin results in significant increase in salivary protective factors secretion, mediated by the esophago-salivary reflex. The impact of the upper esophageal mucosal exposure to acid and pepsin on salivary secretory response remains unknown.

Aims

To investigate the rate of salivary protective factors secretion during the upper esophageal mucosal exposure to acid and pepsin and to compare with the corresponding results recorded during the lower esophageal mucosal exposure, in the same group of asymptomatic volunteers.

Methods

The study was conducted in 10 asymptomatic volunteers. Salivary samples were collected during the esophageal mucosal exposure to saline, followed by acid/pepsin and the final saline, using the esophageal perfusion catheter. Salivary bicarbonate and non-bicarbonate buffers were analyzed using TitraLab. Salivary mucin and protein were quantified through PAS and Lowry methodologies, respectively, whereas PE₂ using radioimmunoassay. Statistical analysis was performed using Σ-Stat software.

Results

The rate of salivary bicarbonate secretion was significantly higher (3.1-fold) during the upper versus the lower esophageal mucosal exposure to acid and pepsin (87.5 ± 14.4 vs. 28.0 ± 7.70 μEq/min, p < 0.05). The volumes of saliva, pH, salivary protein, mucin and PE₂ were similar in both esophageal perfusions.

Conclusions

Threefold stronger secretion of salivary bicarbonate could be a major factor protecting the upper esophageal mucosa. This phenomenon may represent an ultimate defense mechanism potentially preventing further complications within the upper esophageal mucosa; however, it needs to be confirmed in patients of gastroesophageal reflux disease.     

Effect of Mosapride Combined with Esomeprazole Improves Esophageal Peristaltic Function in Patients with Gastroesophageal Reflux Disease: A Study Using High Resolution Manometry

Background

Whether addition of prokinetics to proton pump inhibitors improves esophageal peristalsis and symptoms in patients with gastroesophageal reflux disease (GERD) remains unknown.

Aim

We evaluated the effect of mosapride, a 5-HT₄ agonist, and PPI cotherapy in patients with GERD on esophageal motility using high-resolution manometry (HRM).

Method

This study was designed as a double-blind, randomized, placebo-controlled trial. Patients with GERD were allocated to a group either taking 40 mg esomeprazole plus 30 mg mosapride or taking esomeprazole plus placebo. Symptom assessment and the HRM study were conducted before drug treatment and after 4 weeks.

Results

Of 50 patients enrolled, 24 in the mosapride group (49 years old, 15 males) and 19 in the placebo group (43 years old, nine males) completed the study. Approximately 79 % of the patients had normal peristaltic function. Treatment response was not different between the two groups (79 vs. 68 %). Mosapride cotherapy tended to yield better response in patients with dyspepsia than those without dyspepsia (92 vs. 67 %). Lower esophageal sphincter pressure didn’t change in both groups. Intrabolus pressure decreased in the mosapride group (3.4 ± 3.5 mmHg to 1.4 ± 4.1 mmHg, P < 0.05). Distal esophageal amplitude increased in the mosapride group and not in the placebo group (81 ± 34 to 89 ± 29 mmHg vs. 82 ± 32 to 83 ± 31 mmHg).

Conclusion

Adding mosapride on esomeprazole improved esophageal contractability and lowered intrabolus pressure in patients with GERD. Mosapride and esomeprazole cotherapy tended to yield better response in patients with concomitant dyspepsia.     

Treatment results of laparoscopic surgery in Japanese patients with upside-down stomach

Introduction

Upside-down stomach, an atypical form of esophageal hiatal hernia, is a rare pathology. Due to its anomalous anatomical characteristics, the level of difficulty of laparoscopic surgery is considered to be high. However, as the number of patients is very small in Japan, surgical results have not been fully investigated. We examined the results of surgical treatment for Japanese patients with upside-down stomach.

Materials and methods

The subjects were 11 patients given a diagnosis of upside-down stomach based on upper gastrointestinal tract radiographic imaging and who had undergone laparoscopic surgery at least 6 months prior to this study. Surgical results, postoperative recurrence, and postoperative oral intake of gastric acid-suppressive medications were examined.

Results

The subjects consisted of one man and ten women (91 %). The mean age was 73.0 ± 9.2 years and the mean disease period was 38.7 months. The operation time was 175.5 ± 49.1 min (range 110–280) and the intraoperative blood loss was 122.7 ± 214.9 mL (range 0–550). None of the patients had required conversion to laparotomy. The mean postoperative hospital stay was 8.9 ± 3.4 days (range 7–18) and two patients had persistent dysphagia after surgery, which improved with endoscopic dilatation. While two patients (18 %) had a postoperative recurrence of hiatal hernia, none required reoperation. Two patients (18 %) needed oral gastric acid-suppressive medications postoperatively.

Conclusions

Laparoscopic surgery could be performed in all patients with upside-down stomach. Because of the significant recurrence rate of postoperative esophageal hiatal hernia, the use of a mesh may be required.     

Meat Consumption Is Associated with Esophageal Cancer Risk in a Meat- and Cancer-Histological-Type Dependent Manner

Background

We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer.

Aims

The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer.

Methods

We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case–control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case–control studies were included.

Results

The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98–1.46) for total meat, 1.55 (95 % CI 1.22–1.96) for red meat, 1.33 (95 % CI 1.04–1.69) for processed meat, 0.72 (95 % CI 0.60–0.86) for white meat, 0.83 (95 % CI 0.72–0.96) for poultry, and 0.95 (95 % CI 0.76–1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat.

Conclusions

Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer.     

Endoscopic Management of Esophageal Cancer After Definitive Chemoradiotherapy

Background

Concurrent chemoradiotherapy (CRT) is a potentially curative non-surgical option for locally advanced esophageal cancer, with pathological complete response (CR) ranging from 13 to 49 %. The rate of persistent and recurrent disease within the esophagus remains high at 40–60 %, and treatment of these tumors may improve disease-free survival. The aim of this review is to assess the efficacy of salvage endoscopic therapies for recurrent esophageal cancer.

Methods

Medline and Embase were searched for relevant studies published in the English-language literature that reported use of endoscopic modalities, including photodynamic therapy (PDT), endoscopic mucosal resection (EMR), and spray cryotherapy, as salvage therapies for esophageal cancer.

Results

A total of 12 studies were identified. In small case series of PDT, CR varied from 20 to 100 %, with 1-, 3-, and 5-year overall survival rates of 65–80, 34–47, and 36 %, respectively. Data from three studies of EMR in squamous cell cancer show CR in 50 % of cases, with 3- and 5-year overall survival of 56–81 and 49 %, respectively. Endoscopic spray cryotherapy has recently been used in this setting with an observed CR of 37.5 %.

Conclusions

Endoscopic salvage therapies are options for those patients with disease limited to the superficial esophageal wall and those who are unfit to undergo salvage esophagectomy. Widespread application of endoscopic salvage therapies is limited by the lack of awareness and guidelines for endoscopic surveillance post-CRT and limited data on the effectiveness of endoscopic therapies.     

Complete mesocolic excision with D3 lymph node dissection in laparoscopic colectomy for stages II and III colon cancer: long-term oncologic outcomes in 168 patients

Background

There is emerging evidence that complete mesocolic excision (CME) for colon cancer produces favorable oncologic outcomes. The applicability of CME technique in laparoscopic colectomy has not been fully explored. The aim of our retrospective study was to evaluate the feasibility of the CME technique with D3 lymphadenectomy in laparoscopic colectomy and its short- and long-term outcomes.

Methods

Between September 2006 and December 2009, 168 laparoscopic colectomies were performed for stages II and III colon cancer. Prospectively, collected data on demographics, tumor characteristics, complications, and outcomes were analyzed retrospectively.

Results

Eighty-seven patients (51.8 %) had stage II colon cancer, and 81 patients had stage III cancer. The mean operative time was 196.0 ± 61.2 min. The overall morbidity rate was 17.8 %, which included anastomotic leak in 10 patients (5.9 %). There was no operative mortality. The number of lymph nodes harvested was 27.8 ± 13.6. With a median follow-up of 57.3 months, locoregional recurrence and systemic metastasis developed in 6 (3.6 %) and 14 patients (8.3 %), respectively. Seven patients died of causes related to cancer, and all had stage III cancer. Disease-free survival at 5-years was 95.2 % for patients with stage II and 80.9 % for patients with stage III.

Conclusions

Standardization of laparoscopic CME and D3 lymphadenectomy is expedient. The technique is associated with acceptable morbidity and provides excellent oncologic outcomes for stage II and stage III colon cancer. A longer follow-up is needed to validate the enhancement of oncological outcome related to this surgical concept.     

Evaluation of esophageal and airway stent placement for patients with advanced and recurrent esophageal cancer

Background

Patients with advanced esophageal cancer frequently experience dysphagia and dyspnea, and relief of such symptoms is important. We wished to clarify the efficacy of endoscopic stent placement in patients with dysphagia or dyspnea caused by advanced esophageal cancer.

Methods

A database of patients with esophageal cancer who underwent esophageal and airway stent insertion between 2005 and 2012 was analyzed retrospectively. Effects and complications of stent insertion, and survival after stent insertion, were investigated.

Results

Eighteen patients were treated by esophageal (n = 10) and/or airway (n = 9) stent placement. Marked improvements in food intake were recognized in eight patients after esophageal stenting. Marked improvements in breathing were observed in all patients after airway stenting. Dysphagia scores in the esophageal stent group as well as dyspnea grades in Common Terminology Criteria for Adverse Events v4.0 (CTCAE 4.0) in the airway stent group were significantly improved (p = 0.0078). In the esophageal stent group, major complications (CTCAE grade ≥3) occurred in seven of ten patients (70 %). In the airway stent group, major complications occurred in three of nine patients (33 %). Median survival of all 18 patients was 87.5 (range 13–1952) days after esophageal and/or airway stent placement.

Conclusions

Stent placement is effective for the improvement of malignant dysphasia and dyspnea caused by advanced esophageal cancer.

     

Esophageal Intraepithelial Eosinophils in Dysphagic Patients with Gastroesophageal Reflux Disease

Background

Patients with gastroesophageal reflux disease (GERD) often complain of dysphagia and are frequently found to have intraepithelial eosinophils on esophageal biopsy.

Aim

The aim of this study was to investigate the relationship between dysphagia and the number of intraepithelial eosinophils in patients with GERD.

Methods

Review of all patients studied in our esophageal function laboratory from 1999 to 2007 identified 1,533 patients with increased esophageal acid exposure. Patients who complained of dysphagia without mechanical or motor causes were identified and divided into three groups based on whether dysphagia was their primary, secondary or tertiary symptom. A control group consisted of randomly selected GERD patients with no dysphagia. The highest number of intraepithelial eosinophils per high-power field (HPF) in biopsies from the squamocolumnar junction (SCJ) and esophageal body was compared across groups.

Results

There were 71 patients with unexplained dysphagia. Dysphagia was the primary symptom in 13 (18%), secondary symptom in 34 (48%), and tertiary symptom in 24 (34%) patients. The number of eosinophils differed between the four groups, with the highest number in those with dysphagia as the primary symptom (P = 0.0007). This relationship persisted whether biopsies were from the SCJ (P = 0.0057) or esophageal body (P = 0.0096).

Conclusion

An association exists between the number of intraepithelial eosinophils and dysphagia in GERD patients, with the highest number of eosinophils in those with the primary symptom of dysphagia.     

Is Intercellular Space Different Among Layers in Normal Esophageal Mucosa? An Electron Microscopic Study

Background/Introduction

Dilatation of intercellular space (IS) of esophageal epithelial cells is described as a sensitive early marker for epithelial damage by refluxate. Esophageal epithelia are morphologically subdivided into three layers according to the shape of the cells and nuclei. Meanwhile, ten transmission electron microscopy (TEM) photographs and ten randomly selected measurements per photo from gastroesophageal reflux disease (GERD) patients have been widely accepted without any theoretical criticism. We assumed that the IS differs among each layer and thus studied IS according to subdivided layers of normal esophageal epithelium. We also evaluated an optimal number of IS measurements per photograph.

Materials and Methods

Esophagogastroduodenoscopy was performed in 15 healthy adults without any symptom of GERD, taking biopsies from mucosa above 5 cm from the squamo-columnar junction. Tissues were handled and prepared for TEM, verifying three layers of esophageal mucosa, i.e., squamous cell layer, prickle cell layer, and basal layer. Ten digital photomicrographs were taken from each three layers by TEM, and ISs were measured with a computerized image analysis program. For the method of measuring IS, 5, 10, 20, 30, and 40 measurements per photomicrograph were respectively performed by four different examiners. Mean value and intraclass correlation coefficient (ICC) was also yielded.

Results

Mean IS of lower esophagus irrelevant to three epithelial layers were 0.39 ± 0.30 ??m. When subdivided into three layers, however, mean IS of squamous cell layer was 0.62 ± 0.23 ??m, prickle cell layer 0.23 ± 0.19 ??m, and basal layer 0.55 ± 0.36 ??m, with their difference statistically significant (p < 0.05). On the other hand, ICC of 5, 10, 20, 30, and 40 measurements were 0.688, 0.917, 0.837, 0.790, and 0.765, respectively.

Conclusions

Mean IS values of each three layers of esophageal epithelium in normal subjects were significantly different, and reconsideration of the standard measurement method is needed. Ten measurements per photo had an adequate inter-observer agreement.     

Aberrant methylation of the MSH3 promoter and distal enhancer in esophageal cancer patients exposed to first-hand tobacco smoke

Purpose

Polymorphisms in MSH3 gene confer risk of esophageal cancer when in combination with tobacco smoke exposure. The purpose of this study was to investigate the methylation status of MSH3 gene in esophageal cancer patients in order to further elucidate possible role of MSH3 in esophageal tumorigenesis.

Methods

We applied nested methylation-specific polymerase chain reaction to investigate the methylation status of the MSH3 promoter in tumors and matching adjacent normal-looking tissues of 84 esophageal cancer patients from a high-risk South African population. The Cancer Genome Atlas data were used to examine DNA methylation profiles at 17 CpG sites located in the MSH3 locus.

Results

Overall, promoter methylation was detected in 91.9 % of tumors, which was significantly higher compared to 76.0 % in adjacent normal-looking esophageal tissues (P = 0.008). When samples were grouped according to different demographics (including age, gender and ethnicity) and smoking status of patients, methylation frequencies were found to be significantly higher in tumor tissues of Black subjects (P = 0.024), patients of 55–65 years of age (P = 0.032), males (P = 0.037) and tobacco smokers (P = 0.015). Furthermore, methylation of the MSH3 promoter was significantly more frequent in tumor samples from smokers compared to tumor samples from non-smokers [odds ratio (OR) = 31.9, P = 0.031]. The TCGA data confirmed significantly higher DNA methylation level at the MSH3 promoter region in tumors (P = 0.0024). In addition, we found evidence of an aberrantly methylated putative MSH3-associated distal enhancer element.

Conclusion

Our results suggest that methylation of MSH3 together with exposure to tobacco smoke is involved in esophageal carcinogenesis. Due to the active role of the MSH3 protein in modulating chemosensitivity of cells, methylation of MSH3 should further be examined in association with the outcome of esophageal cancer treatment using anticancer drugs.     

Totally laparoscopic resection with natural orifice specimen extraction (NOSE) has more advantages comparing with laparoscopic-assisted resection for selected patients with sigmoid colon or rectal cancer

Purpose

The purposes of this study were to compare the short-term outcomes of natural orifice specimen extraction (NOSE) and laparoscopic-assisted resection for sigmoid colon cancer or rectal cancer and to appraise whether totally laparoscopic resection with NOSE had more advantages compared with conventional laparoscopic-assisted resection.

Methods

Sixty-five patients who underwent totally laparoscopic resection with NOSE were assigned to NOSE group, and 132 patients who underwent laparoscopic-assisted resection were assigned to laparoscopic-assisted (LA) group. Data of all 197 cases were reviewed. Short-term outcomes (including operative outcomes, gastrointestinal recovery, hospital stay, and complication) of the two groups were compared.

Results

Mean numbers of lymph nodes harvested were 17.0?±?8.3 and 18.9?±?11.6 in NOSE group and LA group, respectively, (P?=?0.248); mean operative times were 111.6?±?25.4 min and 115.3?±?23.0 min in the two groups (P?=?0.384); and the mean blood losses in these two groups were 70.2?±?66.1 ml and 126.3?±?58.6 ml, respectively, (P?P?P?=?0.002) in NOSE group and LA group, respectively. Hospital stay in NOSE group were 9.0?±?1.9 and 9.9?±?2.0 days in LA group. Incidences of peri-operative complications were 6.2 and 17.2 % in the two groups, respectively (P?=?0.031).

Conclusions

Without compromising oncologic outcome, totally laparoscopic resection with NOSE had more advantages including less blood loss, less pain, faster recovery of intestinal function and shorter hospital stay compared with laparoscopic-assisted resection for selected patients with sigmoid colon cancer or rectal cancer.     

Endoscopic Minor Papilla Sphincterotomy in Patients with Santoriniceles Reduces Pain and Improves Quality of Life

Background

Pancreas divisum patients with focal obstruction of the minor papilla and resulting dilation of the dorsal pancreatic duct [a santorinicele (SC)] have been reported to improve with endoscopic sphincterotomy of the minor papilla (ESMP). In this study, we assess the long-term efficacy of ESMP in SC patients.

Methods

A retrospective review of the endoscopic database was performed. Fifteen patients with SCs were identified. A follow-up questionnaire was mailed to patients to assess for changes in quality of life (QOL), narcotic use, hospital admissions, and pain after ESMP.

Results

Fifteen patients were mailed questionnaires and 11 responses were obtained. The average pain score prior to ESMP was 8.6/10 (SD ± 1.7) and significantly decreased to 2.7/10 (SD ± 2.0) (p < 0.05) after treatment. Six patients required narcotics before ESMP and none used narcotics for recurrent pancreatic type pain after. Nine patients had recurring admissions for pancreatitis prior to ESMP while only two were admitted after treatment. Mean QOL score prior to ESMP was 4.5/10 (SD ± 2.7) and increased significantly to 8.4/10 (SD ± 1.3) (p < 0.05) with two patients rating their QOL at 10/10.

Conclusions

QOL, narcotic use, hospital admissions, and pain scores all improved with ESMP. Endoscopic therapy for this uncommon condition appears both justified and potentially curative.     

Esophageal Squamous Cell Carcinoma: Assessing Tumor Angiogenesis Using Multi-Slice CT Perfusion Imaging

Objectives

The purpose of this study was to investigate the correlation between multi-slice computed tomographic perfusion imaging (CTPI) parameters and immunohistologic markers of angiogenesis in esophageal squamous cell carcinoma (ESCC).

Methods

Fifty patients with histologically proven esophageal squamous cell carcinoma were enrolled in this study. All subjects underwent multi-slice CT perfusion scan. The hemodynamic parameters of vascular tumor, including blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were generated. All the ESCC specimens were stained immunohistochemically to identify CD31 for quantification of microvessel density (MVD). CTPI parameters were correlated with MVD by using Pearson correlation analysis.

Results

The value of CT perfusion parameters of ESCC were as follows: BF 116.71 ± 47.59 ml/100 g/min, BV 6.74 ± 2.70 ml/100 g, MTT 6.42 ± 2.84 s, PS 13.82 ± 6.25 ml/100 g/min. The mean MVD of all 50 tumor specimens was 34.44 ± 19.75. The PS values were significantly higher in ESCC patients with involvement of lymph node than those without involvement of lymph node (p < 0.01). Blood volume and permeability surface were positively correlated with MVD (p < 0.01), whereas no significant correlation was observed between MVD and BF or between MVD and MTT.

Conclusions

Blood volume and permeability surface were positively correlated with MVD. CTPI could reflect the angiogenesis in ESCC.     

Clathrin heavy chain is a useful immunohistochemical marker for esophageal squamous intraepithelial neoplasia

Background

Recent advances in the endoscopic diagnosis and treatment of esophageal cancer have facilitated the detection and treatment of minute tumors, necessitating the accurate histopathological diagnosis of early esophageal cancer or precancerous lesions. This study evaluated the usefulness of immunohistochemical analysis (IHC) of clathrin heavy chain (CHC) as a marker for early esophageal cancer.

Methods

The immunoreactivity of CHC was analyzed in 409 esophageal specimens using a tissue array. Immunoreactivities of CHC, p53, and Ki67 were then compared in 44 endoscopically resected specimens.

Results

CHC expression was significantly stronger in the cytoplasm of esophageal squamous cell carcinomas compared with non-tumor specimens in the tissue array. CHC expression in endoscopic specimens was significantly stronger in the cytoplasm of high-grade intraepithelial neoplasias and superficial carcinomas than in benign squamous epithelium and low-grade intraepithelial neoplasias. The sensitivity and specificity of CHC for the diagnosis of esophageal lesions were 75 and 96 %, respectively. These accuracies were comparable with those of p53 (43 and 98 %) and Ki67 (68 and 100 %). In addition, the sensitivity was increased by using a combination of markers as follows: 80 %, CHC + p53; 78 %, CHC + Ki67; 90 %, CHC + p53 + Ki67.

Conclusions

CHC detected by IHC may be a useful marker for the pathological diagnosis of esophageal squamous intraepithelial neoplasia.     

XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms in Esophageal Cancer Risk: A Meta-Analysis

Background

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair.

Aim

To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis.

Methods

Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012.

Results

According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053–1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093–1.624, P = 0.005).

Conclusions

Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.     

Intravenous 64-multi-detector row CT-cholangiography of porcine livers: a feasibility study with definition of the temporal window for optimal bile duct delineation

Background/purpose

To assess the feasibility of intravenous 64-multi-detector row computed tomography (CT)-cholangiography of porcine livers with definition of the temporal window for optimal bile duct delineation.

Methods

Six healthy Landrace pigs, each weighing 28.97 ± 2.99 kg, underwent 64-multi-detector row CT-cholangiography. Each pig was infused with 50 ml of meglumine iotroxate continuously over a period of 20 min and, starting with the initiation of the infusion, 18 consecutive CT scans of the abdomen at 2-min intervals were acquired. All series were evaluated for bile duct visualization scores and maximum bile duct diameters as primary study goals and bile duct attenuation and liver enhancement as secondary study goals.

Results

Of the 16 analyzed biliary tract segments, maximum bile duct visualization scores ranged between 4.00 ± 0.00 and 2.83 ± 1.47. Time to maximum bile duct visualization scores ranged between 10 and 34 min. Average bile duct visualization scores for the 10- to 34-min interval ranged between 3.99 ± 0.05 and 2.78 ± 0.10. Maximum bile duct diameters ranged between 6.47 ± 1.05 and 2.65 ± 2.23 mm. Time to maximum bile duct diameters ranged between 24 and 34 min. Average bile duct diameters for the 10- to 34-min interval ranged between 6.00 ± 0.38 and 2.40 ± 0.13 mm.

Conclusions

Intravenous 64-multi-detector row CT-cholangiography of non-diseased porcine liver is feasible, with the best bile duct delineation acquired between 10 and 34 min after initiation of the contrast agent infusion.     

Neoadjuvant chemotherapy can improve outcome of colorectal cancer patients with unresectable metastasis

Background

The prognosis for colorectal cancer (CRC) patients with unresectable metastases is dismal. This study compared outcomes of different metastatic treatments.

Patients and methods

We collected 653 CRC cases with unresectable metastases including 490 cases receiving primary tumor resection then chemotherapy (surgery group) and 163 patients receiving neoadjuvant chemotherapy then did or did not receive operations (chemotherapy (C/T) group) from 2004 to 2010. The statistical endpoint was overall survival from the date of diagnosis.

Results

In the C/T group, 124 (76 %) patients received an operation after 9.0?±?6.2 months of chemotherapy, including 57 (34.9 %) patients with curative surgery. The C/T group had a higher proportion of T4 lesions (37.4 %) than the surgery group (26.9 %). Survival of the C/T group was longer than that of the surgery group (28.8?±?8.8 vs. 24.3?±?7.5 months; p?=?0.043). Survival of 57 patients receiving curative surgery was 36.0?±?6.3 months, which was significantly better than that of the 67 patients receiving palliative resection (25.2?±?5.6, p?<?0.001). In the surgery group, 42 (8.6 %) patients received curative metastasectomy after 8.5?±?7.1 months of postoperative chemotherapy; survival was 30.8?±?7.8 months, which was significantly better than that of patients who did not receive metastasectomy (22.4?±?6.3 months). In multivariate analysis, poor differentiation, lymphovascular invasion, isolated cancer nodules, clinical risk score, and curative surgery were independent prognostic factors of overall patient survival.

Conclusions

Neoadjuvant chemotherapy can improve outcome of CRC patients with unresectable metastases.