Randomized controlled trial of intravenous sedation vs general anesthesia for esophageal dilation with percutaneous endoscopic gastrostomy in esophageal cancer patients.

BACKGROUND: Esophageal squamous cell cancer (ESCC) is mostly diagnosed in its later stages, when patients present with dysphagia and weight loss. Esophageal dilation with percutaneous endoscopic gastrostomy (PEG) is a common surgical procedure in patients with locally advanced ESCC because of tumor obstruction and enteral nutrition support during neoadjuvant or definitive concurrent chemoradiotherapy (CCRT). Esophageal dilation with PEG is widely performed under general anesthesia (GA) with endotracheal intubation. AIM OF THE STUDY: To determine the overall success rate of completing this procedure using intravenous (IV) sedation with dexmedetomidine (DEX) relative to GA and to compare its perioperative conditions, including procedure times, pain scores (visual analog scale), adverse events, and costs. SETTINGS: Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Thailand. PATIENTS AND METHODS: Prospective randomized controlled trial (RCT) of locally advanced ESCC patients who had dysphagia and needed esophageal dilation with PEG between January 2020 and December 2021. Esophageal dilation (using a Savary-Gilliard dilator) and PEG were performed using the pull technique. RESULTS: Seventy patients were randomly assigned to either the DEX group (n = 34) or the GA group (n = 36). All patients in both groups underwent successful surgery. The DEX group had a significantly shorter procedure time, lower procedure cost, and lower total hospital cost than the GA group. However, there were no significant between-group differences in pain scores or length of hospital stay. There were no serious adverse events in either group; however, the GA group had some incidences of sore throat, transient hoarseness, and atelectasis. CONCLUSION: This study found that IV sedation with DEX during esophageal dilation with PEG was as effective and safe as using GA.

Achievement of benchmark outcomes by a young surgical attendant performing pancreatoduodenectomies.

PURPOSE: Pancreatoduodenectomy is a challenging procedure for young general surgeons, and no benchmark outcomes are currently available for young surgeons who have independently performed pancreatoduodenectomies after completing resident training. This study aimed to identify the competency of a young surgeon in performing pancreatoduodenectomies, while ensuring patient safety, from the first case following certification by a General Surgical Board. METHODS: A retrospective review of data from the university hospital was performed to assess quality outcomes of a young surgical attendant who performed 150 open pancreatoduodenectomies between July 13, 2006, and July 13, 2020. Primary benchmark outcomes were hospital morbidity, mortality, postoperative pancreatic fistula, postoperative hospital stay, and disease-free survival. RESULTS: All benchmark outcomes were achieved by the young surgeon. The 90-day mortality rate was 2.7%, and one patient expired in the hospital (0.7% in-hospital mortality). The overall morbidity rate was 34.7%. Postoperative pancreatic fistula grades B and C were observed in 5.3% and 0% of patients, respectively. The median postoperative hospital stay was 14 days. The 1- and 3-year disease-free survival were 71.3% and 51.4%, respectively. CONCLUSION: Pancreatoduodenectomy requires good standards of care as it is associated with high morbidity and mortality. As only one surgeon could be included in this study, our benchmark outcomes must be compared with those of other institutions. CLINICAL TRIAL REGISTRATION: The study was registered at Thai Clinical Trials Registry and approved by the United Nations (registration identification TCTR20220714002).

Oncoproteomic and gene expression analyses identify prognostic biomarkers for second primary malignancy in patients with head and neck squamous cell carcinoma.

Patients with head and neck squamous cell carcinoma are at increased risk of developing a second primary malignancy, which is associated with poor prognosis and early death. To help improve clinical outcome, we aimed to identify biomarkers for second primary malignancy risk prediction using the routinely obtained formalin-fixed paraffin-embedded tissues of the index head and neck cancer. Liquid chromatography-tandem mass spectrometry was initially performed for candidate biomarker discovery in 16 pairs of primary cancer tissues and their matched normal mucosal epithelia from head and neck squamous cell carcinoma patients with or without second primary malignancy. The 32 candidate proteins differentially expressed between head and neck cancers with and without second primary malignancy were identified. Among these, 30 selected candidates and seven more from literature review were further studied using NanoString nCounter gene expression assay in an independent cohort of 49 head and neck cancer patients. Focusing on the p16-negative cases, we showed that a multivariate logistic regression model comprising the expression levels of ITPR3, KMT2D, EMILIN1, and the patient's age can accurately predict second primary malignancy occurrence with 88% sensitivity and 75% specificity. Furthermore, using Cox proportional hazards regression analysis and survival analysis, high expression levels of ITPR3 and DSG3 were found to be significantly associated with shorter time to second primary malignancy development (log-rank test P = 0.017). In summary, we identified a set of genes whose expressions may serve as the prognostic biomarkers for second primary malignancy occurrence in head and neck squamous cell carcinomas. In combination with the histopathologic examination of index tumor, these biomarkers can be used to guide the optimum frequency of second primary malignancy surveillance, which may lead to early diagnosis and better survival outcome.

Clonal relationship of synchronous head and neck cancer and esophageal cancer assessed by single nucleotide polymorphism-based loss of heterozygosity analysis.

BACKGROUND: The prognoses of head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC) are poor, especially when both tumors occur at the same time. We examined the clonal relatedness of HNSCCs with synchronous ESCCs to confirm whether the second tumors were metastasis or separate second primary malignancies (SPMs) using loss of heterozygosity (LOH) analysis. METHODS: Twenty-one pairs of formalin-fixed paraffin-embedded tissue from HNSCC patients with synchronous esophageal cancer were analyzed by single nucleotide polymorphism (SNP) array using the Illumina HumanCytoSNP FFPE-12 BeadChip (San Diego, CA), which contains approximately 300,000 probes. LOH was identified using Nexus Copy Number software (El Segundo, CA). RESULTS: Comparing the LOH pattern between HNSCC and paired ESCC, we found that 20 out of 21 paired tissues had a high number of discordant LOHs (LOH identified solely in the primary HNSCC but not in synchronous ESCC at the same genomic location) and a low number of concordant LOHs (LOH at the same genomic location in both HNSCC and ESCC). Only one case fell into the undetermined category. Therefore, these 20 ESCCs were classified as SPMs or second field tumors (SFTs). Moreover, the HNSCC patients with molecularly confirmed esophageal SPM had significantly poorer survival than the other patients. CONCLUSIONS: We propose the use of a genome-wide SNP array as a tool to differentiate metastatic tumors from SPM/SFT. The SNP array offers genome-wide LOH information that earlier microsatellite analysis studies lack. The ability to accurately identify SPM should contribute to a better treatment plan and follow-up care of these patients.

Thermally Induced Denaturing Energetics of Human Blood Plasma Albumin by Differential Scanning Calorimetry (DSC) as an Indicator for Breast Cancer Diagnosis in Female Patients.

Cancerous invasion yields unusual metabolisms providing a significant amount of peptide albuminomes that modulate albumin stability via binding. The study aimed at the investigation of the thermal stability of human plasma albumin with breast cancer of various stages by means of differential scanning calorimetry (DSC). Blood plasma was drawn from 11 female breast cancer patients and 50 healthy volunteers of homogeneous demographics. Plasma samples and their albumin-enriched fractions were subjected to DSC scanning between 37 and 90°C at 5°C/min rate. For normal blood plasma, a characteristic signature of DSC tracing was observed. And, the deconvolution of DSC thermograms revealed the recognition of thermal transition of albumin. It was found that denaturing temperature of albumin increased with increasing breast cancer staging which implied the increase in albuminome/peptide abundance produced by cancerous invasion. The analysis of albumin denaturing energetics based on rational approximation of the simple Lumry-Eyring model demonstrated that thermal transition of free albumin and albuminome-bound form attained energetic levels expressed as apparent activation energy (Eapp ± s.e.) of 132.68 ± 14.21 and 46.76 ± 8.42 Kcal/mol corresponded to the schemes dominated by irreversible alteration and by reversible unfolding, respectively. Thus, Eapp value may indicate the degrees of cancerous invasion. It was proposed that Eapp may be used as an indicator to diagnose and assess the prognosis of breast cancer.

Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and Clinicopathological Factors in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67) in ESCC patients. OBJECTIVE: To study the correlation between SCCA, CYFRA 21-1, Ki-67, and clinicopathological factors in ESCC patients. MATERIAL AND METHOD: Pretreatment SCCA and CYFRA 21-1 serum levels were measured, while the expression of Ki-67 was assessed on tumor tissue. The associations between these biomarkers, clinicopathological factors, and overall survival were analyzed. RESULTS: One hundred sixty six patients participated in this study. Elevated SCCA and CYFRA 21-1 were found in 78.9% and 50.0% of the patients, respectively, while 42.8% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p = 0.128) to each other nor to age, sex, T N, M location, grade, or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p = 0.010), M1 (p = 0.010), and poor grade (p = 0.015) but not to age, sex, N, or location. Levels of SCCA, CYFRA 21-1, and Ki-67, alone or in any combination, were not correlated to survival of patients. CONCLUSION: The authors showed that Ki-67 in tumor tissue is probably a more reliable marker than serum SCCA and CYFRA 21-1 in predicting the clinical course of ESCC.

The efficacy of cefazolin in reducing surgical site infection in laparoscopic cholecystectomy: a prospective randomized double-blind controlled trial.

BACKGROUND: A prophylactic antibiotic is recommended in open cholecystectomy surgeries, but in laparoscopic cholecystectomies such prophylaxis is controversial. Recent reviews have not found conclusive evidence that routine prophylaxis, especially in low risk patients, is effective. This clinical trial was undertaken to evaluate the efficacy of cefazolin in reducing surgical site infection SSI in laparoscopic cholecystectomies in a sample not screened for high or low risk patients. METHODS: A randomized double-blind controlled trial was conducted in a single university hospital. Scheduled cholecystectomy patients without selection for patient risk factors were randomized into two groups. Pre-operatively, group A patients received a placebo of 10 ml isotonic sodium chloride, and group B patients received 1 g of cefazolin as a prophylactic antibiotic. All patients underwent a standard laparoscopic cholecystectomy, and were followed up for at least 30 days. RESULTS: Two hundred ninety-nine patients were randomized (149 in group A and 150 in group B). SSI occurred in seven patients (2.34 %), five (1.67 %) in the placebo group, and two (0.67 %) in the prophylactic antibiotic group. The difference was not statistically significant (p value = 0.512), and no specific risk factors for post-operative infection were identified. CONCLUSIONS: A single dose of preoperative prophylactic cefazolin has no significant benefit in reducing the incidence of SSI in laparoscopic cholecystectomy. Whether or not to use a prophylactic depends on the individual patient, and the consideration of the attending surgeon.

Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer.

Concurrent chemoradiotherapy (CCRT) induces toxicities from inflammation and immunological suppression. Omega-3 fatty acids, glutamine, and arginine are therapeutic factors that can attenuate such inflammation and promote cellular immunity. The question is whether immunonutrition (IN) during CCRT reduces inflammation and improves the immune function in patients with esophageal squamous cell carcinoma (ESCC). Seventy-one locally advanced ESCC patients being treated with CCRT (5-FU and cisplatin) were randomized into 2 groups. The IN group received a combination of omega-3 fatty acids, glutamine, and arginine, whereas the control group received standard formula. The levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interferon-gamma (IFN), interleukin (IL-6, IL-10), CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes were measured before and during treatment. The levels of CRP (P = 0.001) and TNF (P = 0.014) increased more during treatment in the control group than the treatment group, whereas IFN, IL-6, and IL-10 were similar but not significantly. CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes decreased more in the control group than in the treatment group, but not significantly. Enteral IN during CCRT reduced the increase of inflammatory cytokine levels.

Evaluating synchronous esophageal cancer in head and neck cancer patients using Lugol dye chromoendoscopy.

OBJECTIVE: Routine screening for esophageal cancer in head and neck cancer patients in Thailand is controversial, because of concerns regarding the screening methods and cost effectiveness. Since Lugol dye chromoendoscopy is an effective technique for early detection of squamous cell carcinoma of the esophagus, the objectives of the present study are to evaluate the synchronous esophageal cancer in head and neck cancer patients and the effectiveness of Lugol dye chromoendoscopy for routine screening. MATERIAL AND METHOD: All diagnosed patients with head and neck cancer between September 1, 2009 and June 30, 2011 were enrolled into the study. Both conventional esophagoscopy and Lugol dye chromoendoscopy were done. The incidence of esophageal cancer was calculated. A diagnostic statistical analysis was done to compare the diagnostic properties between conventional esophagoscopy and Lugol dye chromoendoscopy. Univariate and multivariate logistic regression analyses were used to find significant factors associated with esophageal cancer in this study. RESULTS: Eighty-nine head and neck cancer patients were enrolled in this study. The incidence of esophageal cancer in head and neck cancer patients was 12.4% (11/89). Conventional esophagoscopy found a highly suspicious malignant lesion in only six patients, while the Lugol dye chromoendoscopy detected all 11 esophageal cancers. The sensitivity and specificity for conventional esophagoscopy were 54.5% and 100%, respectively, andfor Lugol dye chromoendoscopy were 100% and 70.5%, respectively. The three significant factors that increased the likelihood of synchronous esophageal cancer from univariate analysis were age less than 50 years, presence of dysphagia, and an unstained Lugol dye area ≥10 mm. Howeve, these factors were not statistically significant by multivariate analysis. CONCLUSION: Lugol dye chromoendoscopy is a promising tool to enhance the diagnosis of esophageal cancer among head and neck cancer patients.

Prevalence and virulence factors of Helicobacter pylori isolated from oral cavity of non-disease, gastritis, and gastric cancer patients.

Background/purpose: The oral cavity is considered a reservoir of Helicobacter pylori associated with gastric infection. It aimed to examine the prevalence of H. pylori strains from the oral cavity and gastric tissue of patients with different stage of gastric-diseases. Strains were further characterized for virulence genes, adhesion ability, and inflammation responses. Materials and methods: 11 non-disease, 15 gastritis, and 15 gastric cancer participated in the study. After clinical examination, gastric biopsies, saliva and plaque samples were collected and H. pylori levels were examined by real-time PCR and cultivation. The cagA and vacA genes were investigated from the culture strains. Adhesion ability and pro-inflammatory responses were analyzed in comparison between the presence of virulent genes and disease status. Results: Relatively poor periodontal condition was found among gastric cancer patients. Prevalence of H. pylori-positive was 84.8% and 19.5% by real-time PCR and cultivation, respectively. The cagA and vacA gene-positive strains were 52.6% and 5.3%, respectively, which were found more in gastric cancer patients. The cagA gene-positive strains were found to be higher in gastric cancer patients, and strains had significantly higher adhesion ability and pro-inflammation expressions than the cagA gene-negative strains. Conclusion: Colonization by H. pylori in oral cavity was confirmed, and the cagA gene-positive strains play a crucial role in both adhesion and inflammatory responses. The presence of H. pylori and its virulence gene in oral cavity should be received attention. An eradication of such strains from oral cavity may help to prevent the transmission and recolonization to gastric organs.

Urogenital dysfunction after laparoscopic surgery for rectal or sigmoid colon cancer.

BACKGROUND/OBJECTIVE: Urogenital dysfunction is a common complication after surgery for sigmoid colon or rectal cancers and may result from various causes. Herein, we evaluated urogenital dysfunction and the associated factors after laparoscopic surgery at different follow-up times. METHODS: We conducted a prospective study on 91 patients who were diagnosed with sigmoid colon and rectal cancers and underwent laparoscopic surgery during 2014-2016. Voiding and male and female sexual dysfunctions following surgery were evaluated by the International Prostate Symptom Score (IPSS), International Index of Erectile Function-5 (IIEF-5), and Female Sexual Function Index-6 (FSFI-6), respectively. Urogenital function was compared at pre-surgery and 3 and 12 months postoperatively, and factors associated with urogenital dysfunction were identified. RESULTS: The overall urinary function after surgery was better when compared to that at pre-surgery; however, there was deterioration in both male and female sexual functions. The mean preoperative IPSS, IIEF-5, and FSFI-6 scores were 9.35, 12.18, and 6.09, respectively. The mean differences among IPSS, IIEF-5, and FSFI-6 at 12 months postoperatively and pre-surgery were -3.08 (95% confidence interval [CI] -4.77 to -1.40), -2.57 (95% CI -4.33 to -0.80), and -2.58 (95% CI -4.73 to 0.42), respectively. Multivariate analysis demonstrated that age ≤60 years (odds ratio 4.22) and postoperative complications (odds ratio 2.77) were correlated with erectile dysfunction. CONCLUSION: Voiding function improved after laparoscopic surgery in both sigmoid colon and rectal cancer patients. However, sexual function in both male and female patients was worse. Age ≤60 years and postoperative complications were strongly associated with male sexual dysfunction.

Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Decolonisation is considered a valuable means to reduce Staphylococcus aureus infection rates. However, previous topical strategies targeting the nose or skin had little success, and oral antibiotic-based decolonisation is ill advised because of eradication of the microbiota and development of antibiotic resistance. We previously showed that the probiotic Bacillus subtilis significantly diminished S aureus at the main intestinal colonisation site via specific bacterial interaction in mice; in this study, we tested this probiotic approach to control S aureus colonisation in humans. METHODS: We did a single-centre, phase 2, double-blind, randomised, placebo-controlled trial in adults from the Songkhla region of Thailand who were colonised by S aureus. Eligible participants were adults (aged ≥18 years) without history of intestinal disease, antibiotic treatment, or hospital admission within the previous 90 days. Participants were excluded if they were pregnant, breastfeeding, taking probiotics, or had diarrhoea. Participants were allocated (1:1) to groups by computer randomisation in blocks of four, and research coordinators were masked to group allocation. Participants received 250 mg of probiotic B subtilis MB40 or placebo once per day for 30 days and S aureus colonisation was determined after the last dose was received. The primary outcome was colonisation by S aureus (continuous, mean decrease in colony-forming-unit count) in the intestine (by faecal counts) and nares (by nasal swabs) after intervention (30-day regimen of B subtilis probiotic). This trial is registered with the Thai Clinical Trials Registry, TCTR20210128003. FINDINGS: The trial was done between Jan 29 and June 30, 2021, with enrolment taking place from Jan 29 to April 6, 2021. 115 participants were colonised by S aureus, either in the intestine (n=84), nose (n=50), or both (n=19), and were randomly assigned to treatment (n=55) and placebo groups (n=60). Oral probiotic B subtilis resulted in significant reduction of S aureus in stool (96·8%; p<0·0001) and nose (65·4%; p=0·0002). There were no differences in adverse effects or significant microbiome changes between the intervention and placebo groups. INTERPRETATION: B subtilis probiotic eliminated more than 95% of the total S aureus colonising the human body without altering the microbiota. This probiotic strategy offers several key advantages over presently used decolonisation strategies for potential use in people with chronic or long-term risk of S aureus infection. Furthermore, by establishing a defining role of the intestinal colonisation site, our findings call for revisiting fundamental notions about S aureus colonisation. FUNDING: National Research Council of Thailand and US National Institutes of Health.

Characterization of adhesion, anti-adhesion, co-aggregation, and hydrophobicity of Helicobacter pylori and probiotic strains.

Objectives: To characterize the adhesion ability of nine Helicobacter pylori strains and eight probiotics in human oral keratinocyte cells (H357 cells) in comparison to intestinal cells (Caco-2 and HIEC-6 cells). Subsequently, the anti-adhesion and co-aggregation abilities of the selected probiotic strains on H. pylori strains were investigated. Methods: Nine H. pylori strains, including H. pylori ATCC43504 (type strain), and 8 clinical strains, were isolated from oral samples of three patients (one non-disease, one gastritis patient, and one gastric cancer patient). Eight selected probiotic strains were used, as follows: Lacticaseibacillus paracasei SD1, Lacticaseibacillus rhamnosus SD4, L. rhamnosus SD11, Limosilactobacillus fermentum SD7, L. rhamnosus GG, Limosilactobacillus reuteri ATCC-PTA6475, Lacticaseibacillus casei Shirota, and L. paracasei CNCM I-1572. The adhesion and anti-adhesion abilities of H. pylori and the probiotic strains were investigated in H357, Caco-2, and HIEC-6 cells. Co-aggregation at various pHs, hydrophobicity, and surface receptors of the cell lines for H. pylori strains were examined. Results: All probiotic and H. pylori strains adhered to H357 significantly better than Caco-2, and HIEC-6 cells. Three probiotic strains (SD7, SD4, SD11) showed significantly higher adhesion than others. Of the clinical H. pylori strains, isolates from a gastric cancer patient had the highest adhesion ability to all of the cell lines tested. Probiotic strains that exhibited high adhesion ability provided high anti-adhesion and co-aggregation against H. pylori strains. Acidic conditions encouraged the co-aggregation of probiotics to H. pylori strains. Conclusion: This study provides information relating to the adhesion abilities of clinical H. pylori and probiotic strains to the oral mucosa when compared to the intestinal mucosa. Certain probiotic strains may be useful for the successful eradication of H. pylori infection via anti-adhesion and co-aggregation.

Establishment the cost-effectiveness through set criteria of laparoscopic cholecystectomy.

OBJECTIVE: To assess the set criteria of laparoscopic cholecystectomy (LC) in reducing the length of hospital stay (LOHS), and total treatment expenditure. MATERIAL AND METHOD: The measurement outcomes were prospectively analyzed through the medical record, and self questionnaire of the patients. RESULTS: During the 1-year trial, a total of 122 patients were scheduled for LC. Among these, 85 cases had met the set criteria of low risk clients of both preoperative indicator of a) American Society of Anesthesiologists (ASA) class 1 or 2, and postoperative indicators of b) no surgical drainage, and c) no immediate complication, while 37 cases were excluded due to ASA class 3 or 4, and various reasons. Distributed by the duration of hospital stay, the patients were classified in to three groups; group A was overnight hospital stay, 15 of 85 subjects (17.6%), group B was short hospital stay (within 3 days), 51 of 85 subjects (60.0%), and group C was long hospital stay (more than 3 days), 19 of 85 subjects (22.4%). The mean length of hospital stay (LOHS) was 24 +/- 1.61 hours in group A, 55 +/- 11.16 in group B, and 108 +/- 21.59 in group C, while the average total expenditure was 531.22 +/- 111.09, 665.5 +/- 133.35 and 812.33 +/- 158.62, respectively. For the overnight hospital stay group, the LOHS and the total treatment expenditure was significantly lower the other groups (p < 0.001). The majority of the overnight hospital stay group had rated the patient satisfaction as excellent. CONCLUSION: The set criteria of laparoscopic cholecystectomy (LC) are helpful and establish the cost-effectiveness in terms of reduction of LOHS and total treatment expenditure.

Pretreatment Esophageal Wall Thickness Associated with Response to Chemoradiotherapy in Locally Advanced Esophageal Cancer.

PURPOSE: A multimodality approach using concurrent chemoradiotherapy (CRT) followed by esophagectomy has been the standard treatment in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Computed tomography (CT) is widely utilized to evaluate esophageal cancer before and after CRT. This study evaluated the utility of pretreatment maximal esophageal wall thickness on CT scans to predict treatment outcomes after CRT in patients with locally advanced ESCC. METHODS: Eighty-one patients with T3 locally advanced ESCC, whom were treated completely with CRT with and without surgery, and had available CT scans before and after CRT at a university hospital between 2005 and 2015, were retrospectively reviewed. RESULT: Twenty patients (24.7%) had esophagectomy after neoadjuvant CRT and sixty-one patients (75.3%) had definitive CRT. The maximal esophageal wall thicknesses were measured retrospectively and correlated with the response and survival after treatment. A total of 40% of neoadjuvant CRT patients achieved a pCR. There was a significant difference in pretreatment maximal esophageal wall thickness between the pCR and non-pCR groups (mean 11.9 ± 5.3 mm versus 16.9 ± 3 mm; p = 0.01). Pretreatment maximal esophageal wall thickness < 10 mm was significantly related to better overall survival than ≥ 10 mm (median survival 79 months versus 15 months; HR 3.21, 95%CI 1.14-9; p = 0.02). The neoadjuvant CRT group had significantly better survival than the definitive CRT group (median survival 51 months versus 14.5 months; HR 0.46; 95%CI 0.25-0.85; p = 0.01). CONCLUSION: In our study, pretreatment esophageal wall thickness of T3 locally advanced ESCC is a useful indicator for predicting survival and pCR after treatment.

Correlation of epidermal growth factor receptor mutation, immunohistochemistry, and fluorescence in situ hybridization in esophageal squamous cell carcinoma.

BACKGROUND: The epidermal growth factor receptor (EGFR) has become a promising target for novel anticancer therapy Evaluation of its biological profiles including gene mutation, amplification, and protein expression in esophageal squamous cell carcinoma (ESCC) is essential to establish the EGFR molecular feature(s) suitable to select patients in anti-EGFR therapy. MATERIAL AND METHOD: The subjects' specimens of ESCC at Songklanagarind Hospital were obtained and investigated for EGFR protein expression and gene amplification. Polymerase chain reaction (PCR) was performed to amplify the EGFR DNA product. The mutational status of EGFR exons 19 and 21 was analyzed using direct sequencing. The entire biological profiles of the EGFR were then correlated. RESULTS: There were 48 eligible ESCC specimens. No somatic mutation in the tyrosine kinase domain of EGFR was detected A high level of EGFR protein was exhibited in 22 patients (46%). Twenty-three patients (48%) had shown a high gene copy numbers. However, no direct correlation between EGFR protein and gene status was observed. CONCLUSION: EGFR mutations in the tyrosine kinase domain of exons 19 and 21 were absent in ESCC, whereas, protein overexpression and gene amplification was prevalent. Therefore, selection of ESCC patients for studies with anti-EGFR agents based on protein expression or gene copy number, not gene mutation, is rational.

Initial experience and result of thoracoscopic and laparoscopic esophagectomy.

BACKGROUND: Conventional esophagectomy requires either a laparotomy or a thoracotomy. Currently, the minimally invasive esophagectomy is an evolving alternative to the open technique. OBJECTIVE: Assess and evaluate the early outcomes of the authors' experiences with the minimally invasive esophagectomy for esophageal cancer. MATERIAL AND METHOD: Outcome data were collected prospectively from 28 consecutive patients, 22 men and six women with a mean age of 63 years and a range of 36-77 years. RESULTS: Thoracoscopic esophageal mobilizations were successful in 17 patients. Four patients were converted to open thoracotomy. Laparoscopic gastric mobilizations were successful in eight patients and only one patient was converted to laparotomy. Mortality was one (3.5%), and perioperative morbidity was nine (32%), including pneumonia, pleural effusion, wound infection, anastomosic leakage, and hoarseness. CONCLUSION: Minimally invasive esophagectomy is feasible and can be performed at the Prince of Songkla University Hospital. Optimal results require appropriate patient selection and surgeon experience.

The prognostic value of p53 immunostaining in node-negative breast carcinoma.

BACKGROUND: P53 plays a key role in cell cycle arrest, apoptosis, DNA repair, and angiogenesis. Although some studies have reported as prognostic factor for poor survival in node-positive breast cancer, controversy about possible prognostic index for node-negative still exists. OBJECTIVES: To look for correlations between the expression of the p53 protein and clinicopathological parameters, and to assess its prognostic value in node-negative invasive ductal breast carcinoma. MATERIAL AND METHOD: Immunohistochemistry using formalin-fixed, paraffin-embedded sections from 71 node-negative breast carcinomas in Songklanagarind Hospital. Data were analyzed with respect to tumor size, estrogen receptor, and survival. RESULTS: P53 mutations were found in 12 patients (17%). Expression of p53 was not associated with tumor size, estrogen receptor, and overall survival. Mean follow-up time was 164.4 months (median 163 months). CONCLUSION: P53 expression was not a significant prognostic factor for survival in node-negative breast carcinoma.

Costs and benefits of different methods of esophagectomy for esophageal cancer.

Background A minimally invasive approach to esophagectomy is being used increasingly, but concerns remain regarding the feasibility, safety, cost, and outcomes. We performed an analysis of the costs and benefits of minimally invasive, hybrid, and open esophagectomy approaches for esophageal cancer surgery. Methods The data of 83 consecutive patients who underwent a McKeown's esophagectomy at Prince of Songkla University Hospital between January 2008 and December 2014 were analyzed. Open esophagectomy was performed in 54 patients, minimally invasive esophagectomy in 13, and hybrid esophagectomy in 16. There were no differences in patient characteristics among the 3 groups Minimally invasive esophagectomy was undertaken via a thoracoscopic-laparoscopic approach, hybrid esophagectomy via a thoracoscopic-laparotomy approach, and open esophagectomy by a thoracotomy-laparotomy approach. Results Minimally invasive esophagectomy required a longer operative time than hybrid or open esophagectomy ( p = 0.02), but these patients reported less postoperative pain ( p = 0.01). There were no significant differences in blood loss, intensive care unit stay, hospital stay, or postoperative complications among the 3 groups. Minimally invasive esophagectomy incurred higher operative and surgical material costs than hybrid or open esophagectomy ( p = 0.01), but there were no significant differences in inpatient care and total hospital costs. Conclusion Minimally invasive esophagectomy resulted in the least postoperative pain but the greatest operative cost and longest operative time. Open esophagectomy was associated with the lowest operative cost and shortest operative time but the most postoperative pain. Hybrid esophagectomy had a shorter learning curve while sharing the advantages of minimally invasive esophagectomy.

Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma.

PURPOSE: To assess the status of EGFR, HER-2, and CCND1 at the gene and protein levels in esophageal squamous cell carcinoma. METHODS: Dual-color FISH assays were performed using DNA probes for EGFR/CEP 7, HER-2/CEP 17, and CCND1/CEP 11. The respective proteins, furthermore, was assessed in IHC assays and correlated with patient and tumor characteristics. RESULTS: From 55 ESCCs, 8 (15%) tumors showed gene amplification and 20 (36%) had gene overrepresentation (balanced gene and chromosome 7 polysomy) for EGFR. High-level protein expression was frequent (49%), positively correlated with gene copy numbers (kappa=0.4), and associated with well-differentiated histology (p=0.02). For HER-2, gene amplification was detected in a single tumor (2%) and protein overexpression was rare (9%). CCND1 gene was amplified in 23 (42%) tumors; likewise, CCND1 protein overexpression was common (58%) and prevailed in gene overrepresentation or amplification. Only 1 patient showed gene amplification for both EGFR and CCND1. Survival was not associated with EGFR or CCND1 gene/protein status, whereas negative patients for HER-2 protein had a better survival than positive patients (p=0.04). CONCLUSIONS: Frequent overexpression and gene amplification of EGFR and CCND1 make these molecules and their pathways potential therapeutic targets for ESCC. In addition, EGFR and CCND1 appeared to be independently altered suggesting alternative mechanisms for pathway activation. Therapeutic agents targeting these molecules are urged to be tested in clinical trials and comprehensive biological analyses should be included to properly interpret the outcome.