Para Chandrasoma

Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients

The value of endoscopic surveillance of Barretts esophagus and the appropriate management of high-grade dysplasia remain unclear. Seventeen patients who were referred from endoscopic surveillance programs for management of high-grade dysplasia or adenocarcinoma developing in Barretts esophagus were compared with 35 patients who had a newly recognized Barretts adenocarcinoma, who had not been in a surveillance program. The referral diagnosis in the surveyed group was adenocarcinoma in six and high-grade dysplasia in 11. After repeat endoscopy with aggressive biopsy, two additional patients with adenocarcinoma were identified. Of the nine patients who underwent esophagectomy for high-grade dysplasia, five had invasive adenocarcinoma in the esophagectomy specimen, which had been missed before the operation, despite the fact that the median number of biopsy specimens obtained per 2 cm of Barretts mucosa was 7.8 (range 1.5 to 15.0). Overall, 13 patients in the surveyed group had adenocarcinoma, 12 staged early and one staged intermediate by the WNM classification. Surveyed patients were operated on at an earlier stage than the nonsurveyed patients (10 early, 14 intermediate, and 11 late stage tumors; chi 2 = 15.6, p < 0.01). Despite the presence of adenocarcinoma in 13 of the 17 surveyed patients, their survival was significantly better than that of the nonsurveyed group (chi 2 = 5.8, p < 0.05). Patients referred from surveillance programs for Barretts esophagus have a better outcome and earlier stage tumors than nonsurveyed patients. Inasmuch as multiple biopsy procedures do not exclude the presence of adenocarcinoma, continued surveillance of high-grade dysplasia is dangerous and potentially destructive to surveillance efforts.

Curative Resection for Esophageal Adenocarcinoma Analysis Of 100 En Bloc Esophagectomies

ObjectiveTo document what can be accomplished with surgical resection done according to the classical principles of surgical oncology. MethodsOne hundred consecutive patients underwent en bloc esophagectomy for esophageal adenocarcinoma. No patient received pre- or postoperative chemotherapy or radiation therapy. Tumor depth and number and location of involved lymph nodes were recorded. A lymph node ratio was calculated by dividing the number of involved nodes by the total number removed. Follow-up was complete in all patients. The median follow-up of surviving patients was 40 months, with 23 patients surviving 5 years or more. ResultsThe overall actuarial survival rate at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC) stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%; stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were transmural. Tumor depth and the number and ratio of involved nodes were predictors of survival. Metastases to celiac (n = 16) or other distant node sites (n = 26) were not associated with decreased survival. Local recurrence was seen in only one patient. Latent nodal recurrence outside the surgical field occurred in 9 patients and systemic metastases in 31. Tumor depth, the number of involved nodes, and the lymph node ratio were important predictors of systemic recurrence. The surgical death rate was 6%. ConclusionLong-term survival from adenocarcinoma of the esophagus can be achieved in more than half the patients who undergo en bloc resection. One third of patients with lymph node involvement survived 5 years. Local control is excellent after en bloc resection. The extent of disease associated with tumors confined to the mucosa and submucosa provides justification for more limited and less morbid resections.

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

OBJECTIVE The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.

Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence

Barrett’s esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and csophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify’ biomarkers associated with each stage of the Barrett’s process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett’s intestinal metaplasia (n —14), Barrett’s dysplasia (n =10), Barrett’s adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barren’s esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Alann-Whitney U test). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer panents than in normal esophagus tissues from patients vrith no cancer (P = 0.013). Very high expression levels ([hTERT × 100: β-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett’s esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer ‘field’ effect is present in the esophagus of patients with Barrett’s cancer.

Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen

In the rat model, esophageal adenocarcinoma reproducibly develops following surgically induced duodenal reflux into the esophagus and administration of nitrosamine. In addition, decreasing gastric acid via partial or total gastrectomy increases the prevalence of adenocarcinoma in this model. We questioned whether carcinogen was necessary for cancer development in the gastrectomized model and whether esophageal acidification could reverse the effect of gastrectomy. Three groups of 26 rats each were randomized to a surgical procedure to produce one of the following reflux models: gastroduodenal reflux by esophagojejunostomy, duodenal reflux by total gastrectomy and esophagojejunostomy, or no reflux by Roux-en-Y reconstruction. In a second experiment, 42 rats were operated on to induce duodenal reflux. One week following surgery, they were randomized to receive acidified water (pH 1.8) or tap water. The animals were killed at 24 weeks of age, and the esophagus was evaluated histologically. All animals with reflux had severe esophagitis and 87% developed columnar lining of the distal esophagus. Nearly half (48%) developed adenocarcinoma at the anastomotic site 16 weeks postoperatively and without carcinogen administration. Cancer prevalence did not differ between animals with gastroduodenal or duodenal reflux but tended to be lower in animals receiving acidified water. Duodenoesophageal reflux is carcinogenic in the rat model. Exogenous carcinogen is not necessary for cancer development in gastrectomized rats.

Short-segment Barrett's Esophagus: a prevalent complication of gastroesophageal reflux disease with malignant potential☆

The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett’s esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett’s esophagus were subdivided according to the length of Barrett’s mucosa: short-segment Barrett’s (<3 cm) and extended Barrett’s (≥3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett’s mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett’s and 37 (15%) had extended Barrett’s esophagus. Patients with short-segment Barrett’s esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett’s esophagus had incresed esophageal acid exposure as did 100% of those with extended Barrett’s esophagus. All lengths of Barrett’s mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett’s esophagus had dysplasia. The length of Barrett’s mucosa was ≤3 cm in 25% (4 of 16) of patients with early Barrett’s adenocarcinoma. Short-segment Barrett’s esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.

Clinical Significance of p53 Mutations in Adenocarcinoma of the Esophagus and Cardia

OBJECTIVE To compare the frequency and spectrum of p53 gene mutations in adenocarcinomas of the esophagus and cardia and to compare clinical and pathologic features in patients with p53 mutant and nonmutant cancers. SUMMARY BACKGROUND DATA The p53 gene is commonly mutated in human cancers, and a p53 mutation is reported to be present in more than 50% of esophageal adenocarcinomas. Although many studies have investigated the frequency of p53 protein overexpression in adenocarcinomas of the esophagus or esophagogastric junction, few studies have assessed the frequency and clinical significance of p53 mutations in these tumors. In particular, the prognostic importance of p53 mutation is uncertain. Adenocarcinomas of the esophagus and cardia share many epidemiologic and pathologic features, but it is controversial whether they represent the same tumor. A comparison of the frequency and spectrum of mutations in adenocarcinomas of the esophagus and cardia would test whether these tumors are also similar at the molecular level. METHODS DNA was isolated from microdissected paraffin-embedded tumor tissues of patients who underwent esophagogastrectomy for adenocarcinoma of the esophagus (n = 19), cardia (esophagogastric junction, n = 12), or subcardia (n = 6). Exons 5 to 8 of the p53 gene were analyzed for the presence of mutations using the polymerase chain reaction with single-strand conformation polymorphism and DNA sequencing of bands showing abnormal mobility. The presence of mutation was confirmed by selective hybridization of a mutant-specific oligonucleotide to DNA isolated from the tumor. RESULTS p53 mutations were identified in 18 of 37 (48.6%) tumors. Patients with p53 mutant tumors were significantly younger and had a significantly poorer prognosis. There was a similar prevalence of p53 mutations in adenocarcinomas of the esophagus (53%) and cardia (58%). In contrast, mutations were relatively uncommon in subcardia adenocarcinomas (one mutant tumor [17%]). The types of mutations found in the esophageal and the cardia cancers were also similar. CONCLUSIONS Adenocarcinomas of the esophagus and cardia have a similar frequency and spectrum of p53 gene mutations, suggesting that these tumors have a common pathogenesis. Patients with mutations are younger, have signs of more advanced disease, and have a poorer prognosis than patients without mutations.

Malignant peripheral nerve sheath tumor arising in an adrenal ganglioneuroma in an adult male homosexual

The authors report a case of malignant peripheral nerve sheath tumor arising in an adrenal ganglioneuroma in an adult. This is the first such case occurring in the absence of a history of childhood neuroblastoma treated with radiation, and provides evidence that such a transformation can occur spontaneously. The neoplasm demonstrated a highly malignant biologic behavior with rapid growth, local recurrence, and metastasis.

Isolated cerebral mucormycosis : case report and therapeutic considerations

Cerebral mucormycosis (without associated involvement of and invasion from the nasal sinuses and turbinates) is an extremely rare opportunistic infection of the central nervous system. We report the case of an intravenous drug abuser (who was negative for the human immunodeficiency virus) who presented with hemiparesis on the right side, slurred speech, altered mental status, and an unsteady gait. Imaging studies revealed a large left-side basal ganglia lesion. A stereotactic biopsy obtained a tissue sample that revealed wide, nonseptated hyphal fragments with granulomatous inflammation. The patient was treated with 3 gm of amphotericin B during a 5-month period. The patient had no residual neurological dysfunction after treatment. Open surgical resection was not employed. This case suggests that stereotactic biopsy followed by long-term amphotericin B therapy, in lieu of open surgical resection, represents a viable treatment option for this rare disorder.

Anastomotic line renal artery stenosis after transplantation.

We report on 5 patients with renal artery stenosis after renal transplantation. Renal arteriography showed the stenosis to be localized at the line of arterial anastomosis. The patients presented with refractory hypertension, with or without renal failure, 10 days to 13 months after transplantation. Percutaneous transluminal balloon angioplasty in 4 patients failed in 3 and produced temporary improvement in 1. Resection of the stenosis resulted in dramatic improvement of the clinical state in all 5 patients. Histological examination of the resected stenotic segment revealed a nodular fibrotic lesion at the anastomotic line in all cases, and was associated with extensive calcification in 3. Anastomotic line stenosis should be recognized as a specific entity causing transplant renal artery stenosis. The pathological changes observed explain the failure of transluminal angioplasty and suggest that surgical repair is the treatment of choice. Possible factors in the etiology of anastomotic line stenosis are discussed.