Significant and distinct impacts of sleeve gastrectomy and Roux-en-Y gastric bypass on esophageal acid exposure, esophageal motility, and endoscopic findings: a systematic review and meta-analysis.

BACKGROUND: The lack of standardized objective assessment of esophageal physiology and anatomy contributes to controversies regarding the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on gastroesophageal reflux disease. This study aimed to investigate esophageal acid exposure, esophageal motility, and endoscopic findings before and after SG and RYGB. METHODS: This was a systematic review and meta-analysis of studies reporting at least 1 objective measure of esophageal physiology and/or esophagogastroduodenoscopy (EGD) at baseline and after SG or RYGB. The changes in pH test, manometry, and EGD parameters were summarized. RESULTS: Acid exposure time (AET) and DeMeester score (DMS) significantly increased after SG (mean difference [MD]: 2.1 [95% CI, 0.3-3.9] and 8.6 [95% CI, 2.0-15.2], respectively). After RYGB, both AET and DMS significantly decreased (MD: -4.2 [95% CI, -6.1 to -2.3] and -16.6 [95% CI, -25.4 to -7.8], respectively). Lower esophageal sphincter resting pressure and length significantly decreased after SG (MD: -2.8 [95% CI, -4.6 to -1.1] and -0.1 [95% CI, -0.2 to -0.02], respectively). There were no significant changes in esophageal manometry after RYGB. The relative risks of erosive esophagitis were 2.3 (95% CI, 1.5-3.5) after SG and 0.4 (95% CI, 0.2-0.8) after RYGB. The prevalence rates of Barrett esophagus changed from 0% to 3.6% after SG and from 2.7% to 1.4% after RYGB. CONCLUSION: SG resulted in the worsening of all objective parameters, whereas RYGB resulted in the improvement in AET, DMS, and EGD findings. Determining the risk factors associated with these outcomes can help in surgical choice.

Dietary weight loss intervention provides improvement of gastroesophageal reflux disease symptoms-A randomized clinical trial.

To evaluate the effect of dietary interventions aimed at weight loss in gastroesophageal reflux disease (GERD) symptoms and general health-related quality of life (HRQL) in overweight and obese patients. A population of GERD patients were randomized into two groups: the intervention group received individualized dietary counselling on scheduled appointments throughout 6 months of follow-up (n = 31) and the control group received only informative dietary guidelines on baseline (n = 31). Anthropometric data were monthly collected, and the HRQL score for GERD (GERD-HRQL) and the Health Survey (SF-36) questionnaires were applied on baseline and reevaluated at the end of follow-up. Dietary intervention led to an average weight loss of 4.4 kg (±5.3) and an average BMI reduction of 1.7 kg/m2 (±2.9) compared to an increase in weight of 2.1 kg (±4.4) (p < .001) and an increase in BMI of 1.3 (±6.3) (p = 0.023) in the control group. Individuals in the intervention group had a mean decrease in symptoms of 6.8 (±5.5) points while the control group had worsening of their symptoms with an increase of 3.3 (±4) points (p < .001) in the disease-specific questionnaire. There was a positive association between weight loss and reduction of symptoms as measured by the GERD-HRQL score (r = .49; p < .001). Dietary intervention for 6 months with an individualized low-calorie diet program produces weight loss and a significant improvement in GERD-related symptoms, as well as in HRQL.

AI-assisted discovery of an ethnicity-influenced driver of cell transformation in esophageal and gastroesophageal junction adenocarcinomas.

Although Barrett's metaplasia of the esophagus (BE) is the only known precursor lesion to esophageal adenocarcinomas (EACs), drivers of cellular transformation in BE remain incompletely understood. We use an artificial intelligence-guided network approach to study EAC initiation and progression. Key predictions are subsequently validated in a human organoid model, in patient-derived biopsy specimens of BE, a case-control study of genomics of BE progression, and in a cross-sectional study of 113 patients with BE and EACs. Our model classified healthy esophagus from BE and BE from EACs in several publicly available gene expression data sets (n = 932 samples). The model confirmed that all EACs must originate from BE and pinpointed a CXCL8/IL8↔neutrophil immune microenvironment as a driver of cellular transformation in EACs and gastroesophageal junction adenocarcinomas. This driver is prominent in White individuals but is notably absent in African Americans (AAs). Network-derived gene signatures, independent signatures of neutrophil processes, CXCL8/IL8 expression, and an absolute neutrophil count (ANC) are associated with risk of progression. SNPs associated with changes in ANC by ethnicity (e.g., benign ethnic neutropenia [BEN]) modify that risk. Findings define a racially influenced immunological basis for cell transformation and suggest that BEN in AAs may be a deterrent to BE→EAC progression.

ADC as a predictor of pathologic response to neoadjuvant therapy in esophageal cancer: a systematic review and meta-analysis.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) is part of clinical practice. The aim of this study was to evaluate the role of apparent diffusion coefficient (ADC) as a predictor of pathologic response to neoadjuvant therapy (nCRT) in patients with esophageal cancer (EC). METHODS: The MEDLINE, Embase, and Google Scholar databases were systematically searched for studies using ADC to evaluate response to neoadjuvant therapy in patients with EC. Methodological quality of the studies was evaluated with the QUADAS tool. Data from eligible studies were extracted and evaluated by two independent reviewers. Meta-analyses were performed comparing mean ADC values between responders and non-responders to nCRT in three different scenarios: baseline (BL) absolute values; percent change between intermediate (IM) values and BL; and percent change between final follow-up (FU) value and baseline BL. RESULTS: Seven studies (n = 158 patients) were included. Responders exhibited a statistically significant percent increase in ADC during nCRT (mean difference [MD] 21.06%, 95%CI = 13.04-29.09; I2 = 49%; p = 0.12). A similar increase was identified in the complete pathologic response (pCR) versus non-complete pathologic response (npCR) subgroup (MD = 25.68%, 95%CI = 18.87-32.48; I2 = 0%; p = 0.60). At the end of treatment, responders also exhibited a statistically significant percent increase in ADC (MD = 22.49%, 95%CI = 9.94-35.05; I2 = 0%; p = 0.46). BL ADC was not associated with any definition of pathologic response (MD = 0.11%, 95%CI = - 0.21-0.42; I2 = 85%; p < 0.01). CONCLUSION: These results suggest that ADC can be used as a predictor of pathologic response, with a statistically significant association between percent ADC increase during and after treatment and pCR. ADC may serve as a tool to help in guiding clinical decisions. KEY POINTS: • DWI is routinely included in MRI oncological protocols. • ADC can be used as a predictor of pathologic response, with a statistically significant association between percent ADC increase during and after treatment and pCR.

Predictive Factors of Gastroesophageal Reflux Disease in Bariatric Surgery: a Controlled Trial Comparing Sleeve Gastrectomy with Gastric Bypass.

OBJECTIVE: To evaluate the impact of laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) on gastroesophageal reflux disease (GERD) in patients with obesity. METHODS: Patients with class II or III obesity were treated with LSG or LRYGB. Procedure choice was based on patients and surgeon preferences. GERD symptoms, endoscopy, barium swallow X-ray, esophageal manometry, and 24-h pH monitoring were obtained before and 1 year after surgery. RESULTS: Seventy-five patients underwent surgery (83% female, 39.3 ± 12.1 years, BMI of 41.5 ± 5.1 kg/m2): 35 (46.7%) had LSG and 40 (53.3%) LRYGB. LSG patients had lower BMI (40.3 ± 4.0 kg/m2 vs. 42.7 ± 5.7 kg/m2; p = 0.041) and trend toward lower prevalence of GERD (20% vs. 40%; p = 0.061). One year after surgeries, GERD was more frequent in LSG patients (74% vs. 25%; p < 0.001) and all LSG patients with preoperative GERD continue to have GERD postoperatively. De novo GERD occurred in 19 of 28 (67.9%) of LSG patients and 4 of 24 (16.7%) patients treated with LRYGB (OR 10.6, 95%CI 2.78-40.1). Independent predictors for post-operative GERD were as follows: LSG (OR 12.3, 95%CI 2.9-52.5), preoperative esophagitis (OR 8.5, 95% CI 1.6-44.8), and age (OR 2.0, 95%CI 1.1-3.4). CONCLUSIONS: One year after surgery, persistent or de novo GERD were substantially more frequent in patients treated with LSG compared with LRYGB. LSG was the strongest predictor for GERD in our trial. Preoperative counseling and choice of bariatric surgical options must include a detailed assessment and discussion of GERD-related surgical outcomes.

Achalasia Treatment in Patients over 80 Years of Age: A Multicenter Survey.

Background and Aims: Laparoscopic Heller's myotomy (LHM), per oral endoscopic myotomy, and pneumatic dilatation are well-established methods to treat achalasia. The ideal treatment algorithm in elderly patients is, however, still elusive. This multicenter study aims to evaluate outcomes and changes in routine therapeutic options in patients >80 years of age. Methods: Worldwide high-volume centers for the treatment of achalasia were surveyed. Therapeutic options and outcomes in patients >80 years of age were reviewed. Results: Eighty-five (54% men, mean age 84 ± 4 years) patients were studied. Primary treatment was endoscopic in 43 (51%) patients, surgical in 39 (46%) patients (30 LHM, 9 cardioplasty + gastrectomy), and medical in 3 (4%) patients. Four centers tailored treatment based on age (14% of the patients). Secondary treatment was necessary in 34 (40%) patients: 30 of them with endoscopic treatment as primary treatment. LHM was performed in 20 patients and endoscopic treatment in 14 patients. A total of 11 (13%) patients had complications after LHM. Seven had LHM or cardioplasty + gastrectomy as primary treatment. Four had LHM as secondary treatment. The mean time of hospitalization was 4 ± 2 days for those who did not have complications, and 7 ± 6 days for those who had complications. Conclusions: Most specialized centers do not tailor treatment based on advanced age. Treatment of the oldest-old patients should be based solely on their physiologic and mental health, not their age. Endoscopic treatment has a high rate of recurrence and gastrectomy a high rate of complications in his population. LHM seems to be a safe option with good outcomes in this population.

Neutrophil-Lymphocyte Ratio as a Marker of Progression from Non-Dysplastic Barrett's Esophagus to Esophageal Adenocarcinoma: a Cross-Sectional Retrospective Study.

BACKGROUND: Immune imbalance and inflammation have been suggested as key factors of Barrett's esophagus (BE) pathway towards adenocarcinoma. The neutrophil-lymphocyte ratio (NLR) indirectly reflects the relation between innate and adaptive immune systems and has been studied in premalignant conditions as a biomarker for cancer diagnosis. Our aim was to investigate if increasing values of NLR correlated with advancing stages of BE progression to dysplasia and neoplasia. METHODS: We retrospectively analyzed data of patients with biopsies reporting BE between 2013 and 2017 and with a complete blood count within 6 months from the endoscopy, as well as patients with esophageal adenocarcinoma (EAC). NLR was calculated as neutrophil count/lymphocyte count. Cases (n = 113) were classified as non-dysplastic BE (NDBE, n = 72), dysplastic BE (DBE, n = 11) and EAC (n = 30). RESULTS: NLR progressively increased across groups (NDBE, 1.92 ± 0.7; DBE, 2.92 ± 1.1; EAC 4.54 ± 2.9), with a significant correlation between its increasing value and the presence of dysplasia or neoplasia (r = 0.53, p < 0.001). NLR > 2.27 was able to diagnose EAC with 80% sensitivity and 71% specificity (area under the curve = 0.8). CONCLUSION: NLR correlates with advancing stages of BE progression, a finding that reinforces the role of immune imbalance in EAC carcinogenesis and suggests a possible use of this marker for risk stratification on surveillance strategies.

Interaction of HSD11B1 and H6PD polymorphisms in subjects with type 2 diabetes are protective factors against obesity: a cross-sectional study.

BACKGROUND: The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). The generation of cortisol from this reaction may increase intra-abdominal cortisol levels and contribute to the physiopathogenesis of obesity and metabolic syndrome (MetS). The relationship of HSD11B1 rs45487298 and H6PD rs6688832 polymorphisms with obesity and MetS was studied. We also studied how HSD11B1 abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) gene expression is related to body fat distribution. METHODS: Rates of obesity and MetS features were cross-sectionally analyzed according to these polymorphisms in 1006 Brazilian white patients with type 2 diabetes (T2DM). Additionally, HSD11B1 expression was analyzed in VAT and SAT in a different cohort of 28 participants with and without obesity who underwent elective abdominal operations. RESULTS: Although polymorphisms of the two genes were not individually associated with MetS features, a synergistic effect was observed between both. Carriers of at least three minor alleles exhibited lower BMI compared to those with two or fewer minor alleles adjusting for gender and age (27.4 ± 4.9 vs. 29.3 ± 5.3 kg/m2; P = 0.005; mean ± SD). Obesity frequency was also lower in the first group (24.4% vs. 41.6%, OR = 0.43, 95% CI 0.21-0.87; P = 0.019). In the second cohort of 28 subjects, HSD11B1 gene expression in VAT was inversely correlated with BMI (r = - 0.435, P = 0.034), waist circumference (r = - 0.584, P = 0.003) and waist-to-height ratio (r = - 0.526, P = 0.010). CONCLUSIONS: These polymorphisms might interact in the protection against obesity in T2DM individuals. Obese individuals may have decreased intra-abdominal VAT HSD11B1 gene expression resulting in decreasing intra-abdominal cortisol levels as a compensatory mechanism against central and general adiposity.

Factors Associated to Abnormal Distal Esophageal Exposure to Acid and Esophagitis in Individuals Seeking Bariatric Surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) impacts choice and outcomes of bariatric surgery. However, GERD diagnosis based solely on symptoms yields inaccurate results. OBJECTIVE: To determine the factors associated with a positive 24h pH-monitoring (pH-test) or esophagitis in patients with severe obesity seeking bariatric surgery. SETTING: Private practice. METHODS: 93 patients with severe obesity underwent prospective evaluation for GERD symptoms, body composition, upper gastrointestinal endoscopy, esophageal manometry and pH-test. Correlation analyses were performed. RESULTS: 50 patients (53.8%) had GERD symptoms, 49 (52.7%) had esophagitis and 33 (35.5%) had a positive pH-test. Among patients with GERD symptoms, 18% had normal pH-test and no esophagitis, while 34.9% of patients without GERD symptoms had positive pH-test, esophagitis or both. Factors independently associated with positive pH-test were esophagitis (PR:3.08, 95%CI: 1.4-6.9, P = 0.006) and defective lower esophageal sphincter (PR:1.88, 95%CI: 1.09-3.21, P = 0.02). Factors independently associated with esophagitis were hiatal hernia (PR: 2.46; 95%CI: 1.6-3.7, P<0.001), GERD symptoms (PR:2.09; 95%CI: 1.3-3.4, P = 0.003) and positive pH-test (PR:1.82; 95%CI: 1.2-2.7, P = 0.003). The combined presence of GERD symptoms and esophagitis had a low positive predictive value for a positive pH-test (57%). On the other hand, the absence of both GERD symptoms and esophagitis had a 90% predictive value for a negative pH-test. CONCLUSIONS: Investigation for GERD before bariatric surgery should consist of routine upper endoscopy and GERD symptom evaluation in all patients. Patients with GERD symptoms and no esophagitis may need a pH-test for GERD diagnosis. Prospective studies are needed to understand significance of GERD diagnosis prior to bariatric surgery.

Concomitant PPARα and FXR Activation as a Putative Mechanism of NASH Improvement after Gastric Bypass Surgery: a GEO Datasets Analysis.

BACKGROUND: Compared to non-surgical weight loss (Diet), weight loss after Roux-en-Y gastric bypass (RYGB) results in greater rates of non-alcoholic steatohepatitis (NASH) resolution. Changes in bile acid physiology and farnesoid X receptor (FXR) signaling are suspected mediators of postoperative NASH improvement. Recent experimental evidence suggests that upregulation of hepatic peroxisome proliferator-activated receptor α (PPARα) activity might also impact NASH improvement. As FXR partly regulates PPARα, we compared resolution of NASH and changes in hepatic PPARα and FXR gene expression following Diet and RYGB. METHODS: We searched the Gene Expression Omnibus database to identify human studies with liver biopsies containing genomic data and histologic NASH features, at baseline and after Diet or RYGB. Microarray data were extracted for PPARα and FXR gene expression analyses using GEOquery R package v.2.42.0. RESULTS: We identified one study (GSE83452) where patients underwent either Diet (n = 29) or RYGB (n = 25). NASH prevalence was similar at baseline (Diet 76% versus RYGB 60%, P = ns). After 1 year, NASH resolved in 93.3% of RYGB but only in 27.3% of Diet (P < 0.001). Hepatic PPARα and FXR gene expression increased only after RYGB (P < 0.001). These changes were also found when analyzing only patients that resolved NASH (P < 0.01), and patients without NASH at baseline and follow-up (P < 0.05). CONCLUSIONS: Compared to Diet, RYGB results in greater NASH resolution with concurrent upregulation of hepatic PPARα and FXR. Our findings point to concurrent PPARα and FXR activation, triggered by RYGB, as a potential mechanism to improve NASH.

Can different subsets of ineffective esophageal motility influence the outcome of nissen fundoplication?

BACKGROUND: Ineffective esophageal motility (IEM) in patients with gastroesophageal reflux disease includes three different subsets that may affect symptom profiles. Our aim was to assess symptoms and functional outcome in patients with erosive esophagitis according to different subsets of IEM, before and after Nissen fundoplication (NF). METHODOLOGY: A retrospective study with prospective follow-up of 72 patients with reflux esophagitis and IEM in whom open NF was performed. Based on principal manometric esophageal body motility disorder, patients were divided in three groups: predominantly low-amplitude (LAC, N = 38), non-propulsive (NPC, N = 18), and simultaneous low-amplitude esophageal contractions (SC, N = 16). Patients underwent symptomatic questionnaire and stationary esophageal manometry before and 6 months, 1 year, and 3 years after surgery. RESULTS: Preoperatively, patients in NPC and SC groups had higher mean scores of dysphagia, without statistical significance as opposed to the LAC group (p = 0.239). Postoperative dysphagia occurred in 36 patients, without statistical significance between groups regarding dysphagia grades (p = 0.390). A longer duration of postoperative dysphagia was noted in the SC group (p < 0.05). Improvement of nadir values of contraction amplitudes in distal esophagus occurred postoperatively in all groups, significantly higher in LAC (p < 0.001). CONCLUSION: Three years after NF, successful symptomatic and functional outcome was achieved in analyzed groups of patients with erosive esophagitis regardless of IEM subtype.

Epidermal growth factor receptor expression in esophageal adenocarcinoma: relationship with tumor stage and survival after esophagectomy.

Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts EA staging and patient survival. Methods. In this historical cohort, consecutive patients with EA managed between 2000 and 2010 were considered eligible for the study. Surgical specimens of patients treated with transhiatal esophagectomy were evaluated to establish EGFR expression and tumor differentiation. Staging was classified according with tumor-node-metastasis (TNM) system. Survival was determined according to either medical register or patient's family contact. Results. Thirty-seven patients who underwent esophagectomy without presurgical chemotherapy or radiotherapy were studied. EGFR expression was found in 16 patients (43%). EGFR expression was more frequent as higher was the TNM (I and II = 0% versus III = 47% versus IV = 100%; P < 0.001). Average survival in months was significantly shorter in the group of patients with EGFR expression (10.5 versus 21.7; P = 0.001). Conclusions. In patients with esophageal adenocarcinoma treated with transhiatal esophagectomy, EGFR expression was related to higher TNM staging and shorter survival. EGFR expression might be assumed as a prognostic marker for esophageal adenocarcinoma.

The role of gastro-oesophageal pressure gradient and sliding hiatal hernia on pathological gastro-oesophageal reflux in severely obese patients.

BACKGROUND AND AIMS: The relationship between gastro-oesophageal pressure gradient (GOPG), sliding hiatal hernia (SHH) and gastro-oesophageal reflux disease (GORD) is under investigation. We assessed whether GOPG and SHH are predictors of pathological reflux in severely obese patients. METHODS: Ninety-four consecutive patients were prospectively studied with oesophageal manometry, 24-h pH monitoring, upper gastrointestinal endoscopy and barium swallow X-ray. Inspiratory and expiratory GOPGs were measured at manometry testing, whereas SHH was characterized by X-ray. Patients were classified as having physiological or pathological reflux depending on pH monitoring. Patients with oesophagitis but normal pH testing were excluded. RESULTS: Eighty-nine patients composed the study sample (25 men, 38.3+/-11.1 years; BMI 45+/-6.9 kg/m). Sixty-two patients (70%) had pathological reflux, whereas 27 patients (30%) had physiological reflux. Pathological reflux was predicted either by inspiratory GOPG [prevalence ratio (PR) =1.05; 95% confidence interval (CI): 1.03-1.08; P<0.001] or by expiratory GOPG (PR=1.07; 95% CI: 1.03-1.11; P=0.001). Accordingly, an increment of 1 mmHg in inspiratory and expiratory GOPGs raises the risk of pathological reflux in 5 and 7%, respectively. Pathological reflux was also predicted by SHH (PR: 1.54, 95% CI: 1.19-2.00; P=0.001), which increases the risk of abnormal reflux in 54%. CONCLUSION: In severely obese patients, either inspiratory GOPG, expiratory GOPG or SHH are predictors of pathological reflux. These findings give pathophysiological support to the high prevalence of GORD in this population.

The impact of gastric bypass on gastroesophageal reflux disease in patients with morbid obesity: a prospective study based on the Montreal Consensus.

OBJECTIVES: To assess the impact of gastric bypass (GBP) on gastroesophageal reflux disease (GERD) based on Montreal Consensus. METHODS: In this study, 86 patients (25 men; aging 38 +/- 12 years; body mass index 45 [35-68 kg/m2]) were investigated for GERD before GBP and 6 months later. Esophageal and extraesophageal syndromes were assessed based on Montreal Consensus. Esophageal acid exposure and gastric pouch acidity were also evaluated. RESULTS: Overall prevalence of GERD was 64% before GBP and 33% after GBP (P < 0.0001). Typical reflux syndrome (TRS) was present in 47 patients (55%) preoperatively and disappeared in 39 of them (79%) post-GBP. Out of 39 patients with no symptoms, 4 (10%) developed TRS postoperatively (P < 0.0001). The chief TRS complaint changed from heartburn pre-GBP (96%) to regurgitation post-GBP (64%). Esophageal mucosa improved in 27, was unchanged in 51, and worsened in 8 patients (P = 0.001) in regard of esophagitis. Extraesophageal syndromes were present in 16 patients preoperatively and in none but one post-GBP (P = 0.0003). GERD-related well being and use of proton pump inhibitors were both improved after GBP. Total acid exposure decreased from a median (interquartile range, 25%-75%) of 5.1% (range, 2-8.2) to 1.1% (range, 0.2-4.8), P = 0.0002. Most patients (86%) showed and acid gastric pouch in fasting conditions post-GBP. CONCLUSIONS: GBP ameliorated GERD syndromes in most patients 6 months after the procedure, resulting in quality of life improvement and less proton pump inhibitors usage. Whether regurgitation post-GBP corresponds to reflux disease or bad eating behavior deserves further studies.

Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma.

BACKGROUND: In western societies, the prevalence of adenocarcinoma of the gastroesophageal junction has increased in recent years. It is commonly accepted today that esophageal adenocarcinoma develops from a premalignant lesion: Barrett's esophagus. This type of carcinoma is hardly diagnosed at early stages, which results in significant mortality. Molecular biology studies have shown that most malignant tumors originate from the interaction between inherited characteristics and external factors, which may cause genetic changes that interfere with the control over the differentiation and growth of cells in susceptible individuals. p21 (WAF1/CIP1) has a key role in the regulation of the cell cycle, and its immunohistochemical expression has been investigated in several tumors, showing that it influences the prognosis of various neoplasms. AIM: To check the prevalence of p21 protein expression in patients with esophageal adenocarcinoma diagnosed in the last 5 years by the Group for Surgeries of the Esophagus and Stomach of "Hospital de Clínicas de Porto Alegre", RS, Brazil. METHODS: The study population consisted of 42 patients with esophageal adenocarcinoma diagnosed by the Group for Surgeries of the Esophagus and Stomach between January 1998 and December 2002. The expression of p21 protein was determined by immunohistochemistry using primary antibody, p21, clone SX118, code M7202 (Dako), and assessed according to the immunoreactive scoring system. RESULTS: Of 42 analyzed patients, 83.3% were male and older than 40 years. Among these, 56.2% were submitted to curative resection: total gastrectomy and transhiatal esophagogastrectomy. The remaining patients were submitted to palliative surgery or did not undergo any surgical treatment. Only five patients received adjuvant chemotherapy and radiation therapy, either alone or combined. Advanced disease (stages III and IV) was detected in 78.6% of the patients. Only nine patients were positive for p21, according to the immunoreactive scoring system. CONCLUSION: p21 was expressed in 9 of 42 patients (21.4%) with esophageal adenocarcinoma diagnosed in the last 5 years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre. In our patient population, the accumulation of p21 did not play a key role in the carcinogenesis of esophageal adenocarcinoma.

Prevalence of p21 immunohistochemical expression in esophageal adenocarcinoma / Prevalência da expressão imunoistoquímica da proteína p21 em adenocarcinoma do esôfago

BACKGROUND: In western societies, the prevalence of adenocarcinoma of the gastroesophageal junction has increased in recent years. It is commonly accepted today that esophageal adenocarcinoma develops from a premalignant lesion: Barrett's esophagus. This type of carcinoma is hardly diagnosed at early stages, which results in significant mortality. Molecular biology studies have shown that most malignant tumors originate from the interaction between inherited characteristics and external factors, which may cause genetic changes that interfere with the control over the differentiation and growth of cells in susceptible individuals. p21 (WAF1/CIP1) has a key role in the regulation of the cell cycle, and its immunohistochemical expression has been investigated in several tumors, showing that it influences the prognosis of various neoplasms. AIM: To check the prevalence of p21 protein expression in patients with esophageal adenocarcinoma diagnosed in the last 5 years by the Group for Surgeries of the Esophagus and Stomach of "Hospital de Clínicas de Porto Alegre", RS, Brazil. METHODS: The study population consisted of 42 patients with esophageal adenocarcinoma diagnosed by the Group for Surgeries of the Esophagus and Stomach between January 1998 and December 2002. The expression of p21 protein was determined by immunohistochemistry using primary antibody, p21, clone SX118, code M7202 (Dako), and assessed according to the immunoreactive scoring system. RESULTS: Of 42 analyzed patients, 83.3 percent were male and older than 40 years. Among these, 56.2 percent were submitted to curative resection: total gastrectomy and transhiatal esophagogastrectomy. The remaining patients were submitted to palliative surgery or did not undergo any surgical treatment. Only five patients received adjuvant chemotherapy and radiation therapy, either alone or combined. Advanced disease (stages III and IV) was detected in 78.6 percent of the patients. Only nine patients were positive for...

RACIONAL: No mundo ocidental, a prevalência de adenocarcinoma da junção esôfago-gástrica vem crescendo nas últimas décadas. Atualmente, é aceito que o adenocarcinoma do esôfago se desenvolve de uma lesão pré-maligna: esôfago de Barrett. Este carcinoma é de difícil diagnóstico nos seus estágios iniciais, o que resulta em mortalidade significativa. O estudo da biologia molecular tem demonstrado que grande parte dos tumores malignos tem origem na interação entre o componente hereditário e influências externas, que em indivíduos predispostos podem ocasionar alterações genéticas que influenciem o controle da diferenciação e crescimento celular. O p21(WAF1/CIP1) tem papel fundamental na regulação do ciclo celular e sua expressão imunoistoquímica tem sido estudada em diversos tumores, mostrando influência no prognóstico de várias neoplasias. OBJETIVO: Verificar a prevalência da expressão da proteína p21 em pacientes com adenocarcinoma de esôfago diagnosticados nos últimos 5 anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre, RS (GCEE/HCPA). PACIENTES E MÉTODOS: A população em estudo foi constituída de 42 pacientes com adenocarcinoma de esôfago diagnosticados no GCEE/HCPA entre janeiro de 1998 e dezembro de 2002. A expressão da proteína p21 foi avaliada por meio de imunoistoquímica, com anticorpo primário, p21, clone SX118, código M7202 da DAKO, e quantificada de acordo com o sistema de escore de imunorreatividade ("Immunoreactive scoring system" - IRS). RESULTADOS: Foram estudados 42 pacientes, 83,3 por cento eram do sexo masculino, com idade superior a 40 anos. Destes, 56,2 por cento foram submetidos a procedimentos cirúrgicos com intenção curativa: gastrectomia total e esofagogastrectomia transhiatal. Os demais foram submetidos a cirurgia paliativa ou não sofreram tratamento cirúrgico. Apenas cinco pacientes receberam tratamento adjuvante com quimioterapia e radioterapia, isoladas ou combinadas. Quanto ao estádio, 78,6 por cento ...

Nutritional assessment in patients with squamous cell carcinoma of the esophagus.

BACKGROUND/AIMS: Protein-calorie malnutrition that occurs in patients with squamous cell carcinoma of the esophagus presents defined implications in surgical results. The present study aims to establish a nutritional score for malnutrition to measure the prevalence of protein-calorie malnutrition and to determine parameters with higher discriminatory power for protein-calorie malnutrition diagnosis. METHODOLOGY: Forty-five (45) patients with squamous cell carcinoma of the esophagus (cases) and 90 surgical patients (controls) were analyzed using twelve parameters: percentage of body weight loss, triceps and subscapular skin fold, mid arm circumference and arm muscle circumference, serum total proteins, albumin, transferin, pre-albumin, hematocrit, total lymphocyte count and late hypersensitivity skin tests. Prognostic Nutritional Index was calculated for all patients. RESULTS: There was a statistically significant difference between the two groups (p < 0.05) regarding all evaluated parameters except late hypersensitivity skin tests. Patients were classified as malnourished when presented with six or more altered parameters. Through the proposed score, the prevalence of protein-calorie malnutrition was defined in cases (57.8%) and in controls (7.8%) groups with statistic significant difference (p = 0.001). CONCLUSIONS: The proposed score allowed the diagnosis of malnourished patients, defined the malnutrition prevalence in both groups and established parameters with a greater discriminatory power for the protein-calorie malnutrition diagnosis.

Increasing esophageal length: a comparison of laparoscopic versus transthoracic esophageal mobilization with and without vagal trunk division in pigs.

BACKGROUND: New laparoscopic techniques allow both mediastinal mobilization and performance of a Collis gastroplasty when necessary, and the utility of a transthoracic approach is questioned. The aim of this study was to compare the increase in esophageal length achievable with laparoscopic and transthoracic esophageal mobilization in pigs, and to assess the impact of vagal trunk division on esophageal length. STUDY DESIGN: Baseline esophageal length was obtained in 20 farm pigs by measuring the distance between a stitch placed in the esophagus to a K-wire placed in a vertebral body. Subsequently, laparoscopic and then transthoracic mediastinal mobilization of the esophagus were performed in 15 pigs and the length gain after each procedure recorded. In 7 of 15 animals, the vagal nerve trunks were divided after esophageal mobilization and the increase in esophageal length measured. In five animals, vagal trunk division was performed without earlier esophageal mobilization. RESULTS: Esophageal length gain after laparoscopic mobilization (median 4 mm) was significantly less than that after transthoracic mobilization (median 12 mm, p < 0.0001). Unilateral vagal nerve transection resulted in a median 2.5 mm of esophageal length gain compared with a median of 6.25 mm with division of both vagal trunks. Maximal esophageal lengthening (median 18.5 mm) occurred with a combination of esophageal mobilization and bilateral vagal trunk division. CONCLUSIONS: Esophageal length gain after transthoracic mobilization in normal pigs is significant, and would likely be even greater in patients with gastroesophageal reflux disease with concomitant mediastinal inflammation. Transthoracic mobilization alone likely will allow successful reduction of the gastroesophageal junction below the diaphragm in many patients who might otherwise require a Collis gastroplasty.

Barrett's esophagus can and does regress after antireflux surgery: a study of prevalence and predictive features.

BACKGROUND: To investigate the factors leading to histologic regression of metaplastic and dysplastic Barrett's esophagus (BE). STUDY DESIGN: The study sample consisted of 91 consecutive patients with symptomatic Barrett's esophagus. Pre- and posttreatment endoscopic biopsies from 77 Barrett's patients treated surgically and 14 treated with proton pump inhibitors (PPI) were reviewed. An expert pathologist confirmed the presence of intestinal metaplasia (IM) with or without dysplasia. Posttreatment histology was classified as having regressed if two consecutive biopsies taken more than 6 months apart plus all subsequent biopsies showed loss of IM or loss of dysplasia. Clinical factors associated with regression were studied by multivariate analysis, as was the time course of its occurrence. RESULTS: Histopathologic regression occurred in 28 of 77 patients (36.4%) after antireflux surgery and in 1 of 14 patients (7.1%) treated with PPIs alone (p < 0.03). After surgery, regression from low-grade dysplastic to nondysplastic BE occurred in 17 of 25 patients (68%) and from IM to no IM in 11 of 52 (21.2%). Both types of regression were significantly more common in short (< 3 cm) than long (> 3 cm) segment Barrett's esophagus; 19 of 33 (58%) and 9 of 44 (20%) patients, respectively (p = 0.0016). Eight patients progressed, five from IM alone to low-grade dysplasia and three from low- to high-grade dysplasia. All those who progressed had long segment BE. On multivariate analysis, presence of short segment Barrett's and type of treatment were significantly associated with regression; age, gender, surgical procedure, and preoperative lower esophageal sphincter and pH characteristics were not. The median time of biopsy-proved regression was 18.5 months after surgery, with 95% occurring within 5 years. CONCLUSIONS: This study refutes the widely held assumption that once established, Barrett's esophagus does not change. More than one-third of patients with visible segments of Barrett's esophagus undergo histologic regression after antireflux surgery. Regression is dependent on the length of the columnar-lined esophagus and time of followup after antireflux surgery.

Induction of intrabdominal adhesion formation by a polypropylene mesh prosthesis: an experimental study in rats

A correção de hernias na virilha através de método videolaparoscópico está se tornando procedimento comum que pode, entretanto, levar ao aumento da incidência de aderências...