Search

Abstract Background Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. Methods The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: 30 weeks). Results No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). Conclusion De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.

Aim of this study was to evaluate whether delayed surgery after neoadjuvant chemoradiotherapy (CRT) affects postoperative outcomes in patients with locally advanced squamous cell carcinoma (SCC) of the thoracic esophagus.Esophagectomy is usually recommended within 4 to 6 weeks after completion of neoadjuvant CRT. However, the optimal timing of surgery is not clearly defined.A total of 129 consecutive patients with locally advanced esophageal cancer, treated between 1998 and 2007, were retrospectively analyzed using prospectively collected data. Patients were divided into 3 groups on the basis of timing to surgery: group 1, 30 days (n = 17); group 2, 31 to 60 days (n = 83); and group 3, 61 to 90 days (n = 29). Subsequently, only 2—numerically more consistent—groups were studied, using the median value of timing intervals as a cutoff level: group A, 46 days (n = 66); and group B, >46 days (n = 63).Groups were comparable in terms of patient and tumor characteristics, type of neoadjuvant regimen, toxicity, postoperative morbidity and mortality rates, tumor downstaging, and pathologic complete responses. The overall 5-year actuarial survival rate was 0% in group 1, 43.1% in group 2, and 35.9% in group 3 (P = 0.13). After R0 resection (n = 106), the 5-year actuarial survival rate was 0%, 51%, and 47.3%, respectively (P = 0.18). Tumor recurrence after R0 resection seemed to be inversely related, even if not significantly (P = 0.17), to the time interval between chemoradiation and surgery: 50% in group 1, 40.6% in group 2, and 21.7% in group 3. When considering only 2 groups, the overall 5-year survival was 33.1% in group A and 42.7% in group B (P = 0.64); after R0 resection, the 5-year survival was 37.8% and 56.3%, respectively (P = 0.18). The rate of tumor recurrence was significantly lower in group B (25%) than in group A (48.3%) (P = 0.02).Delayed surgery after neoadjuvant chemoradiation does not compromise the outcomes of patients with locally advanced SCC of the esophagus. Delaying surgery up to 90 days offers relevant advantages in the clinical management of the patients, can reduce tumor recurrences, and may improve prognosis after complete R0 resection surgery. [ABSTRACT FROM AUTHOR]

Implant-based breast reconstruction is part of breast cancer treatment, and increasingly optimized reconstructive procedures exploit highly biocompatible materials to ensure enhanced aesthetic-functional results. Acellular dermal matrices (ADMs) are collagen-based materials that made prepectoral implant placement possible, thanks to their bioactive antifibrosis action. Recently, the first three-dimensional ADM, BRAXON ® Fast , has been produced. Its 3D design represents the technological evolution of BRAXON ® ADM, a flat collagen matrix, and allows for a time-saving complete wrapping of the synthetic prosthesis, thus creating a total biological interface on the implant with patient's tissues. Here, we report our experience on the first 23 eligible patients who received BRAXON ® Fast -assisted prepectoral reconstruction. On a total of 27 breasts, the overall complication rate was 11.1%, including one minor seroma (3.7%), one case of necrosis (3.7%), and one implant removal due to infection. As new-generation devices, 3D ADMs showed an effective performance, allowing to reduce the overall exposure time for implant preparation and providing an optimal safety profile ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Berna, De Grazia, Antoniazzi, Romeo, Dell'Antonia, Lovero, Marchica, Rizzetto and Burelli.)

Screening for genes down-regulated in esophageal cancers (Oncomine database) pinpointed programmed cell death 4 (PDCD4) as one of the most consistently involved. PDCD4 is a new putative tumor suppressor gene implicated in cell transformation, tumorigenesis, and invasiveness. Based on such a biological rationale, the aim of the present study was to evaluate the prognostic value of PDCD4 in esophageal cancers. The immunohistochemical expression of PDCD4 protein was assessed in 111 consecutive esophageal cancers (63 adenocarcinomas and 48 squamous cell carcinomas) and paired non-cancerous samples. PDCD4 immunostaining was significantly lower in cancer samples than in non-cancerous mucosa (p<0.001). In all cases, the native esophageal epithelium consistently expressed nuclear PDCD4, which was significantly less expressed (37/111 cases) or completely lacking (31/111 cases) in the cancer samples. A significant inverse correlation emerged between nuclear PDCD4 expression and tumor stage (p=0.002), pT (p<0.001), nodal metastasis (p=0.038), and with both vascular (p=0.005) and perineural invasion (p=0.004). Nuclear PDCD4 expression was associated with a longer disease-free (p=0.011) and overall (p=0.021) survival. PDCD4 expression predicts the patient outcome in esophageal cancers. Additional functional studies should look into the role of PDCD4 in the multistep process of esophageal oncogenesis also inquiring on the clinical usefulness of the protein expression as prognostic marker in esophageal precancerous lesions.

Background: Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis., Methods: The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10-30 weeks; Group C: >30 weeks)., Results: No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001)., Conclusion: De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.

Objective: Laparoscopic myotomy is the currently preferred treatment for achalasia. Our objectives were to assess the long-term outcome of this operation and preoperative factors influencing said outcome., Methods: Demographic and clinical characteristics and data on long-term outcome were prospectively collected on patients undergoing laparoscopic myotomy for achalasia at our institution from 1992 to 2007. Treatment failure was defined as a postoperative symptom score higher than the 10th percentile of the preoperative score (>9). Logistic regression analysis was used to identify independent preoperative factors associated with successful myotomy., Results: Four hundred seven consecutive patients (220 men, 187 women) underwent the laparoscopic Heller-Dor procedure during the study period; 89 (22%) of them had previously had endoscopic treatment(s). The mortality rate was 0; the conversion and morbidity rates were 1.5% and 1.9%, respectively. The operation failed in 10% of patients (39/407) and the 5-year actuarial probability of being asymptomatic was 87%. Most failures (25/39, 64%) occurred within 12 months of the operation and can be considered as technical failures (incomplete myotomy). Pneumatic dilation overcome the dysphagia in 75% of patients whose surgery was unsuccessful. Considering both the primary surgery and this ancillary treatment, the operation was effective in 97% of achalasia patients. The frequency of sigmoid esophagus, lower esophageal sphincter (LES) resting pressures, and chest pain scores differed statistically between patients with and without recurrences. At multivariate analysis, high preoperative LES pressures (>30 mm Hg) was an independent predictor of a good response. The presence of chest pain and of sigmoid esophagus independently predicted the failure of the procedure., Conclusion: Laparoscopic myotomy can durably relieve dysphagia symptoms. High preoperative LES pressures represent the strongest predictor of a positive outcome, probably reflecting a less severely damaged esophageal muscle.

Objective: Our aim was to compare outcome of vagal-sparing esophagectomy with transhiatal and en bloc esophagectomy in patients with intramucosal adenocarcinoma or high-grade dysplasia., Summary Background Data: Intramucosal adenocarcinoma and high grade dysplasia have a low likelihood of lymphatic or systemic metastases and esophagectomy is curative in most patients. However, traditional esophagectomy is associated with significant morbidity and altered gastrointestinal function. A vagal-sparing esophagectomy offers the advantages of complete disease removal with the potential for reduced morbidity and a better functional outcome., Method: Retrospective review of outcome in patients with intramucosal adenocarcinoma or high grade dysplasia that had a vagal-sparing (n=49), transhiatal (n=39) or en bloc (n=21) esophagectomy., Results: The length of hospital stay and the incidence of major complications was significantly reduced with a vagal-sparing esophagectomy compared with a transhiatal or en bloc resection. Further, postvagotomy dumping and diarrhea symptoms were significantly less common, and weight was better maintained postoperatively with a vagal-sparing esophagectomy. Recurrent cancer has developed in only 1 patient., Conclusion: Survival with intramucosal adenocarcinoma or Barrett's with high-grade dysplasia is independent of the type of resection. A vagal-sparing esophagectomy is associated with significantly less perioperative morbidity and a shorter hospital stay than a transhiatal or en bloc esophagectomy. Further, late morbidity including weight loss, dumping, and diarrhea are significantly less likely after a vagal-sparing approach. Consequently a vagal-sparing esophagectomy is the preferred procedure for patients with intramucosal adenocarcinoma or high grade dysplasia.

Purpose of Review: Barrett's esophagus is a complication of chronic gastroesophageal reflux that results in the replacement of normal stratified squamous epithelium in the distal esophagus by metaplastic columnar mucosa and it carries a 30-fold to 125-fold risk of progression to esophageal adenocarcinoma., Recent Findings: Laparoscopic antireflux surgery has proved durable and effective in treating reflux and reflux-related symptoms in patients with Barrett's esophagus. Recent studies have also focused on the histological changes induced in Barrett's epithelium by antireflux surgery. This article reviews the current literature, analysing the impact of antireflux surgery on both the clinical and the histopathological outcomes., Summary: Recent studies have disproved the widely held assumption that, once established, Barrett's esophagus does not change. Antireflux surgery can achieve a regression of intestinal metaplasia to cardiac mucosa in patients with Barrett's esophagus and may thus alter the natural history of the disease.