Gastrocutaneous fistulas after PEG removal in adult cancer patients: frequency and treatment options.

INTRODUCTION AND AIMS: PEG removal in head and neck cancer patients (HNCPs) is performed after treatment, in case of disease remission and after adequate oral intake is resumed. The PEG tract usually closes spontaneously within 2-3 days. Persistent gastrocutaneous fistula (GCF) is a rare complication after PEG tube removal and is characterized by the persistence of gastric leakage through the fistulous tract for more than 1 month. Our main goal was to access the incidence and the success of a treatment algorithm for GCF in HNCPs. METHODS: Retrospective unicentric study of HNCPs referred for PEG removal between 2014 and 2018. The patients with GCF were selected and their sequential treatment was reviewed. RESULTS: In 331 patients with PEGs removed, 19 (5.7%) GCFs were documented. Medical therapy (4-8 weeks) was performed with clinical success (definitive closure of the GCF) in 12 (63.2%) patients. The remaining seven patients required endoscopic or surgical treatment. In four, endoscopic treatment had technical and clinical success (in three patients with fulguration of the gastric leak edges with argon plasma coagulation, silver nitrate in the path and external orifice, and closure of the internal orifice with hemoclips and in one with an over-the-scope-clip). Only three patients underwent surgery, one due to clinical failure of sequential endoscopic therapy and two had direct surgery. CONCLUSION: GCF occurs rarely after PEG removal in HNCPs. Medical therapy is usually effective and should be maintained for at least 8 weeks. Endoscopic therapy is an effective second-line option with and surgery rarely required.

Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts.

BACKGROUND: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described. AIMS: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis. MATERIALS AND METHODS: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological. RESULTS: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis. CONCLUSION: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

Usefulness of Prophylactic Percutaneous Gastrostomy Placement in Patients with Head and Neck Cancer Treated with Chemoradiotherapy.

Chemoradiotherapy (CRT) has evolved as the preferred organ preservation strategy in the treatment of locally advanced head and neck cancer (HNC). This approach increases malnutrition, and thus, establishing a direct enteral feeding route is essential. To evaluate the usefulness of prophylactic percutaneous endoscopic gastrostomy (PEG) in HNC patients receiving definitive CRT, we performed a prospective evaluation of HNC patients over a 6-month period. Patients and tumor characteristics, nutritional status 30 days after PEG insertion and technique complications were evaluated. We also assessed the long-term PEG usage. Forty-seven PEGs were placed and only 2 patients did not use it. The mean time of PEG use was 131 days (4-255) and mean duration of exclusive utilization was 71 days (4-180). On 30th day after procedure, 34/45 (76 %) patients had lost weight, but only 10/45 (22 %) patients had lost more than 10 % of their initial weight. The most frequent complications were minor peristomal infections, which were correlated with proton-pump inhibitor use before PEG placement (OR 3.91, 95 % CI 1.01-15.2, and p = 0.049). One year later, 19 % of patients in remission continue needing PEG. Enteric nutritional support is essential during and after CRT in HNC patients. Most patients lost weight even with PEG. One-fifth of patients in remission required long-term PEG utilization.

Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease.

We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.

Enterocytic columnar non-goblet cells of Barrett's esophagus--an immunohistochemical demonstration of association with malignant evolution.

Barrett's epithelium (BE), the esophageal columnar-lining with intestinal differentiation, is a premalignant condition predisposing to adenocarcinoma. Columnar cells are the prevalent element of BE, but the hallmark of intestinal differentiation is the goblet population that defines the specialised columnar epithelium (SCE). We have demonstrated that columnar cells adjacent to Barrett's adenocarcinoma (BA) exhibit enterocytic features in areas with and without SCE. Nevertheless, the relationship between malignancy and the presence of these elements is not established. To investigate whether intestinal differentiated cells, other than goblet cells, are associated to neoplasia we compared the prevalence of enterocytic features in columnar elements with and without associated BA through the use of sucrase-isomaltase (SI) immunoreactivity in 31 columnar esophageal segments (CLES) and 12 BA. In metaplasia, SI was only expressed at the columnar cells. Apical staining was exclusive of CLES with SCE. SI was present at the cytoplasm in 22.2% of CLES without SCE. Apical SI occurred in BE with and without carcinoma, similarly in areas with and without SCE (p = 0.11 and p = 0.50, respectively). In areas with SCE, columnar cells with apical SI were more frequent in cases of BE adjacent to carcinoma than in cases without neoplasia but the difference did not reach significance (p = 0.053). In areas without SCE, apical SI was significantly (p = 0.01) more frequent in cases with carcinoma. Apical SI was equally found in neoplastic as in metaplastic areas, with and without SCE, (p = 0.07 and p = 0.40, respectively). In conclusion this study on the frequency of SI on CLES with and without neoplasia demonstrated that additionally to SCE, metaplastic enterocytic cells are also associated with malignancy. It also confirmed that the presence of intestinal features are underestimated if only goblet elements are used for its identification, reinforcing the utility of the immunohistochemical recognition of enterocytic characteristics for establishing the diagnosis of BE.

Verification and unmasking of widely used human esophageal adenocarcinoma cell lines.

For decades, hundreds of different human tumor type-specific cell lines have been used in experimental cancer research as models for their respective tumors. The veracity of experimental results for a specific tumor type relies on the correct derivation of the cell line. In a worldwide effort, we verified the authenticity of all available esophageal adenocarcinoma (EAC) cell lines. We proved that the frequently used cell lines SEG-1 and BIC-1 and the SK-GT-5 cell line are in fact cell lines from other tumor types. Experimental results based on these contaminated cell lines have led to ongoing clinical trials recruiting EAC patients, to more than 100 scientific publications, and to at least three National Institutes of Health cancer research grants and 11 US patents, which emphasizes the importance of our findings. Widespread use of contaminated cell lines threatens the development of treatment strategies for EAC.

Chromosomal analysis of Barrett's cells: demonstration of instability and detection of the metaplastic lineage involved.

UNLABELLED: Barrett's esophagus is lined by columnar and goblets cells with gastric and intestinal characteristics. Despite the association between goblet elements and malignancy, it was not demonstrated that other columnar cells lineages are not related to neoplasia. Chromosomal abnormalities were described in metaplasia adjacent to Barrett's neoplasia, but it is unknown which metaplastic lineages are involved. This work assessed the frequency and the type of chromosomal abnormalities in Barrett's esophagus without neoplasia and performed the identification of the metaplastic cells carrying chromosomal gains. Barrett's esophagus biopsies were collected and processed for short-term cell culture and cytogenetic analysis. Combined immunofluorescence/fluorescence in situ hybridization was performed in cases exhibiting chromosomal gains by using antisera against intestinal (MUC2) and gastric (MUC5AC and MUC6) apomucins and chromosome pericentromeric alpha satellite DNA probes for the chromosomes involved. Each case was scored for the number of spots (0, 1, 2, >2) in 200 nonoverlapping nuclei. Columnar and goblet cells were separately assessed. Short-term cell cultures were achieved in 40/60 cases (67%). There were clonal abnormalities in 27/40 cases (68%) and tetraploid (4n) clones in 10/40 (25%). Structural alterations were detected in 14/40 (35%) with recurrent breakpoints at 1q21, 15q15 and 15q22. Numerical changes (trisomies 7 and 18 and loss of Y) occurred in 16/40 (40%). Gains of chromosomes 7 and 18 were more frequent in columnar than in goblet cells (9.8% vs 0.7% (P<0.05)) and (7.9 vs 1.9% (P<0.05)) respectively. These alterations were detected in cells exhibiting gastric as well as intestinal features and were more frequent in cells without apomucin production. CONCLUSIONS: (1) chromosomal instability is a common finding in Barrett's esophagus without neoplasia. (2) The two metaplastic populations are committed, chromosomal gains being more frequent in columnar nongoblet than in goblet cells. (3) The two metaplastic phenotypes, gastric and intestinal, are equally involved.

Losses of heterozygosity on chromosomes 9p and 17p are frequent events in Barrett's metaplasia not associated with dysplasia or adenocarcinoma.

OBJECTIVE: Losses of heterozygosity (LOH) on chromosomes 9p and 17p frequently accompany malignant transformation of Barrett's esophagus (BE). They have been reported in adenocarcinoma, dysplasia, and adjacent metaplasia of patients with long-segment BE (LSBE). This study aimed to evaluate and compare the frequency of LOH on 9p and 17p in patients with long- and short-segment BE (SSBE) without dysplasia or adenocarcinoma. METHODS: Matched metaplasia and blood DNA were evaluated for LOH on chromosomes 9p and 17p in patients with a previous diagnosis of BE and no dysplasia or cancer. RESULTS: We included 18 patients (12 long-segment BE and six short-segment BE). The overall prevalence of LOH was 61% (10 of 18), with no significant difference between LSBE (58%) and SSBE (50%). The frequencies of LOH on 9p and 17p were similar (35% and 39%, respectively), with 18% of the patients showing losses at both chromosomes. CONCLUSIONS: LOH on 9p and 17p are highly frequent events in BE, even in the absence of dysplasia and adenocarcinoma. The presence of these abnormalities in non-neoplastic epithelium suggests they might be useful markers for risk stratification within endoscopic surveillance programs.

Recurrent columnar-lined esophageal segments--study of the phenotypic characteristics using intestinal markers.

Barrett's metaplasia is recognized by specialized columnar epithelium on the distal esophagus. The events involved in the transformation from squamous to Barrett's epithelium remain unclear. The present study describes the characteristics observed during the recurrence of four cases of columnar-lined esophagus. Red velvet, gastric-like, esophageal mucosa was observed to develop above the anastomosis during follow-up of four patients submitted to surgery for esophageal and junctional adenocarcinoma. The areas of recurrence were associated with reflux symptoms and inflammation, with ulceration in two cases. Biopsies from the upper gastrointestinal endoscopies were examined histologically using periodic acid-Schiff/Alcian blue to detect acid mucins and a monoclonal antibody raised against the enterocytic enzyme sucrase-isomaltase. In all cases the recurrent columnar-lined segments displayed intestinal features recognized morphologically, histochemically, and/or immunohistochemically. There was no evidence of specialized columnar epithelium in three cases. The fourth patient developed specialized columnar epithelium during the tenth year of surveillance. The presence of AB-positive columnar cells was a frequent and early event. Columnar cells with unequivocal apical sucrase-isomaltase were observed only in association with specialized columnar epithelium. Four conclusions were reached: that the development of columnar-lined mucosa without specialized columnar epithelium may be the earliest event in Barrett's metaplasia; that histochemistry is a useful method of recognizing a population with cryptic intestinal features; that acid mucin secretion precedes the production of enterocytic enzymes by columnar cells; and that a cell population with enterocytic differentiation, as assessed by sucrase-isomaltase expression, is associated with the development of specialized columnar epithelium. These characteristics of Barrett's esophagus development are clinically relevant as they suggest that patients with columnar-lined esophagus without specialized columnar epithelium may acquire 'true' intestinal phenotype, justifying them being considered as high- risk patients.

Adenocarcinoma of the esophagogastric junction: could the characteristics of adjacent intestinal metaplasia help in the understanding of biopathogenesis?

We report a case of early adenocarcinoma arising in foci of intestinal metaplasia (IM) at a normal-appearing gastroesophageal junction (GEJ). The tumor infiltrated the submucosa without nodal involvement (T1N0). Non-neoplastic mucosa adjacent to neoplasia had foci of incomplete IM with a band-like CK20 positivity of the surface epithelium and a diffuse CK7 staining of both superficial and deep glands. There were histological features of reflux esophagitis as well as chronic non-atrophic, Helicobacter pylori-related pangastritis, without IM, at the extensively assessed gastric mucosa. In this case, the CK7/20 pattern of IM adjacent to neoplasia, the demonstration of reflux esophagitis, and the absence of IM in the stomach favor the theory that the pathogenesis of IM and associated adenocarcinoma of the GEJ is related to gastroesophageal reflux rather than H. pylori infection.