Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.

OBJECTIVE: Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. METHODS: Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. RESULTS: The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. CONCLUSIONS: PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.     

Prediction of adenocarcinoma in esophagectomy specimens based upon analysis of preresection biopsies of Barrett esophagus with at least high-grade dysplasia: a comparison of 2 systems

Distinguishing Barrett esophagus with high-grade dysplasia (BE-HGD) from intramucosal and submucosal adenocarcinomas on biopsies is challenging, yet important, in the choice of therapy. The current study evaluates preresection biopsies from patients who underwent esophagectomy for at least BE-HGD, to compare the recently published histologic categories by the University of Michigan (UM) and Cleveland Clinic (CC), correlate preresection and final resection diagnosis, and identify histologic features in biopsies that might be predictive of adenocarcinoma on esophagectomy. A total of 112 cases with a consensus biopsy diagnosis (agreement by ≥4 of 7 gastrointestinal pathologists) were statistically analyzed to identify histologic features that predicted adenocarcinoma on resection. Applying the UM criteria to the biopsy series showed excellent agreement with the CC system (κ=0.86) and significant correlation between preoperative and esophagectomy diagnoses (P<0.001). The likelihood of finding carcinoma on resection was significantly higher with the category of HGD with marked glandular distortion cannot exclude intramucosal adenocarcinoma [CC; odd ratio (OR), 2.8; P=0.046] or HGD suspicious for adenocarcinoma (UM; OR, 4.3; P=0.008), compared to HGD alone. The presence of "never-ending" glands (OR, 3.7; P=0.008), sheet-like growth (P<0.001), angulated glands (OR, 8.5; P<0.001), ≥3 dilated glands with intraluminal debris (OR, 2.6; P=0.05), and >1 focus of single-cell infiltration into the lamina propria (OR, 8.9; P<0.001) increased the odds of finding carcinoma on resection. The latter 2 variables remained independent predictors of adenocarcinoma in multivariable analysis. In conclusion, the CC and UM systems show excellent agreement and define histologic categories that can improve prediction of adenocarcinoma on resection.     

Barrett''s esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy.

OBJECTIVE. The authors review the results and outcomes of esophagectomy (prophylactic esophagectomy) for patients with Barrett's esophagus and high-grade epithelial dysplasia (HGD). SUMMARY BACKGROUND DATA. The role of prophylactic esophagectomy for Barrett's esophagus with HGD is controversial, with some authors recommending surgery and others favoring endoscopic surveillance until biopsy diagnosis of carcinoma is made. METHODS. Between 1982 and 1994, 30 consecutive patients with HGD underwent esophagectomy and had the pre- and postoperative pathology reviewed at our institution. The medical records were reviewed to determine patient characteristics, preoperative endoscopic data, surgical approach, operative morbidity and mortality, length of hospitalization, and treatment outcome. Patients were divided into two groups based on whether invasive adenocarcinoma was found in the resection specimen (group 1) or not (group 2). RESULTS. The duration of reflux symptoms was 22 +/- 14 years for group 1 and 9 +/- 11 years for group 2 (p = 0.05). There was one operative death (3.3%) and six complications (20%). In 13 patients (43%, group 1), invasive adenocarcinoma was found in the resected esophagus. The American Joint Committee on Cancer stage for these patients was stage I (8 patients), stage II (2 patients), and stage III (3 patients). One stage I patient died of adenocarcinoma (72 months) in an incompletely excised HGD segment. Other stage I and II patients are alive without adenocarcinoma with an 18-and 63-month mean follow-up, respectively. Outcome for stage III patients was one operative death, one noncancer death (6 months), and one patient with metastatic adenocarcinoma (26 months). For group 2 (57%), there were no adenocarcinoma deaths (40 months). CONCLUSIONS. High-grade epithelial dysplasia is an indication for esophagectomy because of the prevalence of occult adenocarcinoma (43%). Esophagectomy can be performed safely, and survival in patients with completely resected Barrett's esophagus and early-stage adenocarcinoma is excellent.     

Management of gastric remnant carcinoma based on the results of a 15-year endoscopic screening program.

SUMMARY BACKGROUND DATA: Partial gastrectomy for benign peptic ulcer disease is associated with an increased risk of adenocarcinoma of the gastric remnant, especially in patients who are at least 15 years' postgastrectomy. Increasing evidence of mucosal dysplasia is noted on random gastric biopsy and may serve as a histologic marker in the identification of early cancer of the gastric stump. METHODS: From an initial group of 233 patients who underwent gastrectomy for benign peptic ulcer disease between 1960 and 1975, 163 patients began yearly flexible gastroscopy and random mucosal biopsy. Routine histologic studies identified either normal or dysplastic epithelium as well as adenocarcinoma. An average of eight biopsies were taken per endoscopic study. All endoscopic studies were performed by surgical residents under the supervision of one surgical attending. RESULTS: From July 1980 to June 1995, 145 patients completed annual gastroscopy and random biopsy. A total of 2287 endoscopic studies were performed. Fifteen patients were found to have severe dysplasia. Nine (60%) had associated microscopic evidence of adenocarcinoma. Four additional patients had macroscopic adenocarcinoma on endoscopic examination. All 13 patients with cancer were asymptomatic. Six patients continue surveillance who display moderate-to-severe dysplasia alone. The 13 patients with carcinoma underwent completion gastrectomy (R2 nodal dissection) with no evidence of cancer found beyond the gastric wall. These patients averaged 29 years since their original partial gastrectomy. OBJECTIVE: A prospective screening program for gastric remnant cancer was begun to assess the ability to discover early neoplastic changes on random biopsy and to make treatment decisions regarding the efficacy of completion gastrectomy after discovery of carcinoma. CONCLUSIONS: Aggressive annual screening using flexible endoscopy and multiple random biopsy may discover cancer in the gastric remnant and can lead to completion curative gastrectomy in asymptomatic people. Patients who are at least 20 years postpartial gastrectomy for benign disease should be considered for annual endoscopic surveillance.     

Outcomes of dysplasia arising in Barrett's esophagus: a dynamic view

BACKGROUND: The management of dysplasia arising in Barrett's esophagus is controversial. STUDY DESIGN: Twenty patients (group 1, prompt attitude) underwent operation as soon as high-grade dysplasia (HGD) was discovered (n = 8) or just after either the presence of HGD was confirmed (n = 9) or invasive carcinoma (IC) was found (n = 3) in a second set of biopsy samples taken soon after HGD had been discovered. In contrast, esophagectomy in 13 patients (group 2, expectant attitude) was performed only because HGD persisted (n = 4) or turned into IC (n = 4) at endoscopic followup (7 to 23 months) (subgroup 2a, n = 8) or because HGD (n = 2) or low-grade dysplasia (LGD) (n = 3) was disregarded until dysphagia and IC developed (12 to 70 months) (subgroup 2b, n = 5). Skeletonizing en-bloc esophagectomy was performed in 29 patients and four patients (three with HGD and one with mucosal IC in the resected specimen) underwent vagus-sparing esophagectomy. RESULTS: Invasive carcinoma was found in 11 of 24 patients (45.8%) supposed to have only HGD (in repeat biopsies in 3 patients from group 1 and in the resected specimen in eight of 21 patients (38%) operated on for HGD. Metastatic lymph nodes were found in the resected specimen of seven patients (group 1: one of 20 or 5%, versus subgroup 2a: two of eight or 25%, versus subgroup 2b: four of five or 80%; p = 0.001). Unlike none of the 26 patients (0%) with an intramural process, five of the seven patients (71.4%) with an extramural process (one had had disregarded LGD) developed neoplastic recurrence at followup (p < 0.0001). Cancer-related survival in the long term was 100% in group 1 versus 52.5% in group 2 (p = 0.0094). CONCLUSIONS: Invasive carcinoma is present in almost one half of patients with HGD within a Barrett's area. Promptness in the decision regarding an esophageal resection as soon as HGD is found is much safer than expectant observation. Not enrolling a patient with LGD in an endoscopic surveillance program can lead to the development of extramural IC with poor outcomes.     

Barrett's esophagus: pathologic considerations and implications for treatment

Barrett's esophagus (BE) is a complication of chronic reflux that results in the replacement of esophageal squamous epithelium with columnar epithelium. BE is endoscopically recognized and pathologically confirmed. The presence of goblet cells is diagnostic. The pathologist must also determine if dysplasia or invasive cancer is present. Acceptable terms for dysplasia are no dysplasia, indefinite for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). It can be difficult to differentiate HGD from intramucosal cancer (IMC) in an endoscopic biopsy specimen. Treatment based on this differentiation is problematic. Indications for treatment of BE are similar to those of patients without BE. Treatment will not cause clinically significant regression of BE or prevent progression to cancer. Cancer development following successful antireflux surgery is uncommon.     

Discovery of early gastric remnant carcinoma

Partial gastrectomy for benign ulcer disease has been associated with an increased incidence of mucosal dysplasia and invasive adenocarcinoma, particularly in patients who are 15–20 years postresection. Using a planned protocol of routine endoscopic surveillance with biopsy, 163 patients who were at least 10 years postgastrectomy for benign ulcer disease have undergone screening flexible esophagogas-troduodenoscopy (EGD) between July 1980 and August 1994. The completed study group consists of 153 patients who have been examined at least yearly over the 14-year period of surveillance. Routine biopsies from various areas of the gastric remnant have been interpreted for dysplasia or early gastric adenocarcinoma. Patients who evidenced significant dysplasia or adenocarcinoma were offered complete gastrectomy during the study. Results of this ongoing 14-year screening program revealed severe dysplasia of the gastric remnant in 13 patients (8.4%) with eventual findings of adenocarcinoma in seven of this group (54%). These seven patients underwent total gastrectomy with findings of limited disease. Six patients continue to be followed with evidence of dysplasia. During this 14-year screening program, seven patients undergoing completion gastrectomy for early gastric remnant adenocarcinoma continue to be well and free of disease. This aggressive screening program supports the concept that neoplastic change in the gastric remnant is a function of time from the initial gastric resection. Patients identified with early gastric remnant carcinoma benefit by completion gastrectomy. In addition, patients harboring dysplasia in the gastric remnant should continue to be followed in an aggressive screening protocol utilizing random biopsy.     

Oesophagectomy remains the gold standard for treatment of high-grade dysplasia in Barrett's oesophagus.

AIM: The goal of surveillance in Barrett's oesophagus is to detect high-grade dysplasia (HGD). The natural history of HGD is unclear, but because of the reported high risk of coexistent invasive carcinoma, oesophagectomy is currently the gold standard treatment. Recent reports suggest the risk of coexistent tumour may be lower and that the optimum treatment for HGD is continuing surveillance or mucosal ablation treatment, reserving oesophagectomy for those patients with invasive malignancy. To re-examine the role of oesophagectomy we looked at the incidence of invasive cancer in patients undergoing resection for HGD and their subsequent outcome. METHODS: Prospective analysis of 240 patients undergoing oesophagectomy over 6 years under a single surgeon in a single centre. Analysis was focused on patients undergoing oesophagectomy for HGD picked up during Barrett's surveillance endoscopy. The incidence of invasive cancer, morbidity, mortality and survival of this subgroup is reported. RESULTS: Preoperatively, 17 patients were diagnosed with HGD and underwent oesophagectomy. Eleven of 17 (65%) patients had coexistent invasive cancer and six patients had HGD alone in the resected specimens. There was no in-patient mortality, four patients had significant respiratory complications and three patients had radiological/clinical anastomotic leaks. All 6 patients with HGD only are alive to date (3-68 months) and 3 of 11 patients with invasive cancer have died of recurrent disease. CONCLUSION: We continue to advocate oesophagectomy for HGD as the optimum treatment in the light of the high rate of coexistent invasive cancer. Oesophagectomy for HGD can be performed with low morbidity and minimal mortality in a specialist centre. We hypothesize that the lower rates of invasive cancer found in HGD reported by other groups result from interobserver variation in grading of HGD, variability in histological sampling of the resected oesophagus and variability in the endoscopic technique of acquisition of biopsy samples.     

Early gastric cancer. 21-year experience.

From 1963 through 1983, 327 patients underwent resection for gastric adenocarcinoma at Charity Hospital in New Orleans. Fifteen lesions (4.6%) were early gastric carcinoma (limited to the mucosa or submucosa regardless of nodal metastases). These lesions were in eight men and seven women (14 blacks and 1 white), with a mean age of 65.3 years (range: 52-80 years). Upper gastrointestinal series were obtained in 13 (6 suspicious, 2 inconclusive, and 5 normal). By comparison, endoscopy on 11 patients provided a tissue diagnosis in ten patients (90.9%). Surgical procedures ranged from total gastrectomy to a local excision, and every specimen was free of lymph node metastases. Macroscopically, there were six Type I, four Type IIb, and Type IIc, three Type III, and one with two separate lesions (IIa and IIb); microscopically, ten were intramucosal and five had submucosal invasion. Five-year survival calculated by the actuarial method was 64.2% (observed) and 100% (adjusted). This compares with 18.8% (observed) for all 327 patients. Six of the patients with early gastric cancer are alive (range: 16-219 months). The nine patients who died had no evidence of recurrent disease at the time of death. Surgical resection of early gastric carcinoma in the United States offers an excellent prognosis similar to the Japanese experience. Increased detection of gastric carcinoma in its curable stages may be achieved through early endoscopic investigation of symptomatic patients.     

Impact of grade of dysplasia in villous adenomas of Vater's papilla

Therapeutic strategies for villous adenoma of the papilla of Vater remain controversial. This study evaluates the accuracy of preoperative histopathologic diagnosis and the impact of the grade of dysplasia on recurrence as well as on potential alteration of the surgical approach. A series of 32 patients with an adenoma of Vater's papilla who underwent local resection or pylorus-preserving pancreaticoduodenectomy between January 1990 and August 2000 were reviewed retrospectively. Multiple endoscopic biopsies had been performed preoperatively. The histopathology of the preoperatively obtained biopsy specimens and subsequent surgical specimens were evaluated for grade of dysplasia by two pathologists and correlated with the clinical course after operative treatment. Altogether, 3 of 11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy specimens exhibited invasive carcinoma at the postoperative histologic examination (NS). Recurrence was not observed in the 6 patients from the LG dysplasia adenoma group following local resection and benign postoperative histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12 patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%) from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of the papilla of Vater including HG dysplasia appears to be associated with a high risk of exhibiting invasive carcinoma postoperatively and a high rate of recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be offered to patients with an HG dysplasia adenoma.     

Expert pathology review and endoscopic mucosal resection alters the diagnosis of patients referred to undergo therapy for Barrett’s esophagus

Background

Endoscopic therapy has emerged as an alternative to surgical esophagectomy for the management of Barrett’s esophagus (BE)-associated neoplasia. Accurate pretreatment staging is essential to ensure an appropriate choice of therapy and optimal long-term outcomes. This study aimed to assess the frequency with which expert histopathologic review of biopsies combined with endoscopic mucosal resection (EMR) would alter the pretreatment diagnosis of BE-associated neoplasia.

Methods

Patients referred to the Vanderbilt Barrett’s Esophagus Endoscopic Treatment Program (V-BEET) were retrospectively identified. Demographic, histopathologic, and endoscopic data were extracted from the medical record.

Results

For this study, 29 subjects referred for endoscopic staging of BE fulfilled the entry criteria. The referral diagnosis was low-grade dysplasia (LGD) in 3 % (1/29), high-grade dysplasia (HGD) in 62 % (18/29), intramucosal adenocarcinoma (T1a) adenocarcinoma in 17 % (5/29), and invasive adenocarcinoma in 17 % (5/29) of the subjects. Expert histopathologic review of available referral biopsy specimens altered the diagnosis in 33 % (5/15) of the cases. Further diagnostic staging with EMR showed BE without dysplasia in 10 % (3/29), LGD in 14 % (4/29), HGD in 34 % (10/29), T1a adenocarcinoma in 28 % (8/29), and invasive adenocarcinoma in 14 % (4/29) of the patients. The combination of expert histopathologic review and EMR altered the initial diagnosis for 55 % (16/29) of the subjects, with 56 % (9/16) upstaged to more advanced disease and 44 % (7/16) downstaged to less advanced disease.

Conclusions

The practice of combined expert histopathologic review and EMR alters the pretreatment diagnosis for the majority of patients with BE-associated neoplasia. Caution is advised for those embarking on endoscopic or surgical treatment for BE-associated neoplasia in the absence of these staging methods.     

Diagnosis and Management of Barrett-Related Neoplasia in the Modern Era

Whereas in the past, pathologists were hesitant to diagnose high-grade dysplasia in patients with Barrett esophagus, because this diagnosis prompted esophagectomy, current international consensus is that endoscopic treatment is the management for high-grade dysplasia and intramucosal carcinoma. Furthermore, many centers advocate endoscopic ablation for low-grade dysplasia. As such, establishing a diagnosis of dysplasia has become the key step; separation between the grades of dysplasia is less critical. This article offers some criteria for separating dysplasia from reactive changes, discusses pitfalls in interpreting endoscopic mucosal resection specimens, and outlines management strategies.     

Interobserver variability in the diagnosis of crypt dysplasia in Barrett esophagus

Recent morphologic and molecular evidence suggests that dysplasia in Barrett esophagus (BE) begins in the bases of the crypts [crypt dysplasia (CD)] and progresses with time to involve the upper portions of the crypts and surface epithelium. The aim of this study was to evaluate the criteria and reproducibility of diagnosing CD among 6 gastrointestinal pathologists, all with research interest in BE. Six gastrointestinal pathologists evaluated 2 clinical study sets, the first consisting of 40 BE cases [BE: 10, CD: 9, low-grade dysplasia (LGD): 10, high-grade dysplasia (HGD); 9, and intramucosal adenocarcinoma; 2] and the second consisting of 63 cases (BE: 16, CD: 15, LGD: 15, HGD: 15, and intramucosal adenocarcinoma: 2), at least 4 months apart. In between evaluations, all of the pathologists met at 1 hospital (consensus conference) to review the areas of disagreement and establish more objective criteria. Overall, the level of agreement for all cases was moderate (κ=0.44), and the level of agreement did not change significantly after evaluation of the second study set. The highest levels of agreement were obtained for lesions at the low and high end of the spectrum (BE without dysplasia and HGD). Overall, the degree of agreement for CD was moderate after both the first and second study set review (κ=0.44 and 0.46, respectively). However, the degree of agreement for CD was higher than that obtained for LGD in both study sets. In the first study set, 4 or more pathologists agreed with the original CD diagnosis in 78% of cases, and this value did not change significantly after review of the second study set. The observers agreed that characteristic features of CD include the presence of unequivocal dysplastic cells, similar in appearance to traditional LGD, involving any part, or all of the length, of the crypt in the absence of intercrypt surface epithelial involvement. Rare cases of CD may show high-grade cytologic features composed of markedly enlarged nuclei with increased nuclear/cytoplasmic ratio, eosinophilic cytoplasm, irregular nuclear membranes, and loss of polarity. The findings in this study suggest that CD can be diagnosed reliably with a moderate level of interobserver agreement. Long-term and multi-institutional studies should be carried out to further determine the biological and clinical significance and natural history of CD in patients with BE.     

CAGS and ACS Evidence Based Reviews in Surgery. 38: Guidelines for the management of Barrett esophagus with high-grade dysplasia?

Objective: To address the role of esophageal resection and other approaches that are becoming increasingly adopted for the management of Barrett esophagus with high-grade dysplasia (HGD). Data sources: MEDLINE, Cochrane Library and the Trip databases were searched for the terms “Barrett’s or high-grade dysplasia” and “surgery,” “photo-dynamic therapy,” (PDT) “radiofrequency ablation” (RFA) or a combination of these. Study selection: Studies were selected based on the best evidence supporting these commonly used strategies for HGD. Data extraction: The guideline was divided into 4 major components: endoscopic surveillance, mucosal ablation, endoscopic mucosal resection (EMR) and esophagectomy. Main results: Regarding endoscopic surveillance, HGD is an entity distinct and distinguishable from intramucosal carcinoma, and it does not invariably progress to carcinoma. If there is progression, it can be reliably detected at an early, curable stage. Patients undergoing surveillance are reliable for follow-up and are candidates for further therapy if progression is diagnosed. Regarding mucosal ablation, several methods have been reported for HGD; of these, PDT is the most widely used. Radiofrequency ablation has been introduced into practice and is being studied in many of the same centres that have advocated for PDT (RFA is useful for high-risk surgical patients and typically requires multiple endoscopic sessions for therapy and follow-up.) The EMR method has been used to excise discrete esophageal mucosal nodules that were small, flat or poly-poid in nature and that did not invade deeper than the sub-mucosa. Owing to the frequent multifocality of Barrett esophagus, a concomitant mucosal ablative procedure is often required to assure complete eradication of disease (EMR can evaluate and treat discrete mucosal nodules in the esophagus). Most cancers found incidentally in patients with HGD are cured by esophagectomy. It can be performed safely with an operative mortality approaching 1% (it remains the standard of care for patients deemed to have good operative risk). Conclusion: Given the complexities in decision-making in the management of HGD, the nuances in diagnosis and therapy, and the risks associated with either over- or undertreatment, Barrett esophagus with HGD is best managed in a centre of excellence, preferably with input from experienced surgeons, gastroenterologists and pathologists with a focused interest in treating this disorder.     

Endoscopic screening for premalignant changes 25 years after gastrectomy: results of a five-year prospective study

Sixty-three partial gastrectomy patients an average 20 years after surgery were reviewed by endoscopy and biopsy in 1977. No cases of invasive carcinoma were found. The patients were then divided into two groups. Those with moderate epithelial dysplasia (13 patients) were reviewed at 6-12 monthly intervals. One patient developed severe dysplasia but none developed an invasive carcinoma. The remaining patients with either no or mild dysplasia were offered endoscopy after 5 years and 24 agreed. Of the 12 patients with no dysplasia at the outset: 5 still had no dysplasia 5 years later, 3 had mild dysplasia and 4 now had moderate dysplasia. There were 12 with mild dysplasia at the first endoscopy, 9 remained unchanged at the review and 3 had moderate dysplasia. If dysplastic changes in gastric mucosa are pre-malignant, progression to invasive carcinoma would appear to be slow. Even 25 years after gastrectomy only a modest deterioration in the grade of dysplasia was found and no invasive cancer.     

Prognostic significance of high‐grade dysplasia in colorectal adenomas

Aim Colonoscopy to detect and remove polyps has contributed to a reduction in colorectal carcinoma. Three‐year follow up is recommended for patients considered to be at high risk (at least three adenomas, adenoma ≥ 1 cm, villous or high‐grade features). Our study focused on patients diagnosed with high‐grade dysplasia with regard to initial management and follow up. Method A search of patients who had had endoscopic removal of a high‐grade adenoma was carried out. Patients with the following were excluded: follow up of < 1 year, polyposis syndromes, prior colon cancer and a diagnosis of adenocarcinoma within 6 months following initial diagnosis. Results Eighty‐three patients treated between 1999 and 2007 for high‐grade dysplasia (HGD) in a colorectal adenoma were identified. Over a median follow‐up period of 4 years, 53 (64%) developed further adenomatous polyps. Among these, 7% had an adenoma with HGD or an adenocarcinoma. In all these patients, the initial high‐grade adenoma was > 1 cm in diameter. Initial follow‐up colonoscopy was performed on average 7 months following the initial diagnosis. Ten per cent of patients underwent prophylactic segmental resection, and 6% received argon laser therapy. Conclusion The study demonstrates that patients who have a colorectal adenoma > 1 cm with HGD may be at high risk of developing further adenomas with HGD or carcinoma. Close follow up is warranted.     

Minimally invasive esophagectomy for Barrett's esophagus with high-grade dysplasia

BACKGROUND: Barrett's esophagus with high-grade dysplasia (BE/HGD) is associated with invasive carcinoma in 30% to 70% of cases. Esophagectomy is the treatment of choice for patients with BE/HGD but esophagectomy can be associated with high morbidity and mortality. The aim of our study was to report our preliminary experience in applying minimally invasive surgical techniques to esophagectomy for BE/HGD. METHODS: From August 1996 to February 1999, 12 consecutive patients underwent minimally invasive esophagectomy for biopsy-proven BE/HGD. Our consort consisted of 7 men and 5 women; average age was 64 years (range, 40-78 years). All patients underwent a complete laparoscopic or combined laparoscopic and thoracoscopic resection of the esophagus with cervical anastomosis. RESULTS: Mean operative time was 7.8 +/- 2.1 hours, mean intensive care unit stay was 2.6 +/- 2.2 days, and mean length of hospital stay was 8.3 +/- 4.7 days. Five patients (42%) had carcinoma in situ or carcinoma identified on pathologic specimen. Analyses of all resected lymph nodes in the 12 patients were negative for metastatic disease. There were 6 major complications in 5 patients: 1 patient had a small bowel perforation requiring operative repair, 2 patients needed prolonged ventilatory support for respiratory insufficiency, and 3 patients had delayed gastric emptying requiring revision of the pyloromyotomy. The single minor complication in this series was a jejunostomy tube-site infection. There were no conversions to laparotomy or thoracotomy. All patients were alive and free of metastatic disease at a mean follow-up of 12.6 months. CONCLUSIONS: Minimally invasive esophagectomy is a feasible and safe alternative to conventional open esophagectomy for patients with BE/HGD.     

多层螺旋CT在胃癌术前分期中的临床应用

目的探讨多层螺旋CT（MSCT）在胃癌术前分期中的临床应用价值。方法2004年6月至2006年3月间经胃镜活检确诊为胃癌的患者89例，其中男性49例，女性40例，中位年龄63岁。所有患者均在手术前1周内进行MSCT检查。图像由2位资深放射科医师双盲阅读，术前判断患者的肿瘤TNM分期．并与患者的术后病理结果进行对照比较。结果与术后病理诊断比较，MSCT普通轴位图像结合多平面重建法判断胃壁侵犯程度的总准确率为72．3％，其中T1判断准确率为90．0％，T2为82．8％，T3为69．6％，T4为52．4％；判断淋巴结转移情况的总准确率为53．0％，其中N0判断准确率为44．0％，N1为72．0％，N2为46．4％，N3为2／5。MSCT对有远处转移即M1的患者判断准确率为90．0％。结论MSCT对胃癌患者进行术前TNM分期有较高的准确率，可以为胃癌患者术前提供一种无创且易于被接受的检查方法。     

The frequency of advanced adenoma in consulting patients: a nationwide survey in Iceland (2003–2006)

Aim To assess the frequency of advanced colorectal adenomas in consulting patients in Iceland. Method The histological configuration of colorectal adenomas (CRA) found in 3603 patients was classified into tubular (TA), villous (VA) and serrated (SA) and the degree of neoplastic severity into low‐grade dysplasia (LGD), high‐grade dysplasia (HGD), carcinoma in situ (CIS), intramucosal carcinoma (IMC) and submucosal carcinoma (SMC). Advanced CRA were those showing HGD, CIS, IMC and/or SMCs. In patients with two or more adenomas, the adenoma with the highest degree of epithelial neoplasia was selected to record cases. Results Between 2003 and 2006 a total of 19 424 endoscopic examinations (13 572 colonoscopies and 5852 sigmoidoscopies) were performed in Iceland (mean, 4856 endoscopies per year). At histology a mean of 759.3 CRA per year were found. Thus, CRA were found in 15.6% of the colorectal endoscopies performed per year. Out of the 3037 CRA studied, 67% were TA, 29% VA and the remaining 4% SA. LGD was present in 79%, HGD in 15%, CIS in 2.4%, IMC in 1.9% and SMC in 1.9%. Consequently, out of 3037 CRA investigated, 652 (21.5%) were advanced CRA; 71% of these showed HGD, 11% CIS, 9% IMC and 9% SMC. Two‐thirds of the 652 advanced CRA were advanced VA, and more than three‐quarters of 58 advanced CRA with SMC, were advanced VA. Conclusion Advanced VA displaying intraepithelial neoplasia (HGD and CIS) showed a propensity to evolve into invasive carcinoma. Accordingly, VA displaying HGD and CIS might be regarded as biological markers for predicting colorectal cancer risk. This is the first study in which the frequency of CRA and advanced CRA detected in consulting patients is reported on a nationwide basis.     

Risk-reducing total gastrectomy for germline mutations in E-cadherin (CDH1): pathologic findings with clinical implications

Hereditary diffuse gastric cancer is a rare autosomal dominant cancer susceptibility syndrome caused by germline E-cadherin (CDH1) mutations in 40% of cases with a high degree of penetrance. Screening endoscopy has not been useful in identifying early cancer, in part owing to conflicting data concerning site(s) of involvement in the stomach and the lack of endoscopically detectable pathology. Risk-reducing total gastrectomy specimens from 8 asymptomatic adults with germline mutations in the CDH1 gene (3 different pedigrees) were studied using a sequential serial sectioning protocol with submission of the entire stomach for histologic analysis. The presence, size, and distribution of signet ring cell clusters were determined for each section and geographic maps of the invasive foci were constructed and compared with gastrectomy specimens from patients with germline E-cadherin mutation and symptomatic gastric cancer. All but 1 of the asymptomatic patients with germline mutations in the CDH1 gene had negative endoscopic screening. All risk-reducing gastrectomy specimens were macroscopically normal. All contained multiple foci (mean, 10.9) of microscopic intramucosal signet ring cell carcinoma confined to the superficial gastric mucosa; no invasion of submucosa was identified. In situ carcinoma was present in 6/8 cases. The majority of signet ring foci were located in the proximal one third of the stomach, most within oxyntic-type mucosa. The number and size of foci were not related to age, but there was a trend toward more severe disease burden in women. Stomachs from the symptomatic group of patients with germline CDH1 mutations exhibited infiltrative foci with higher Ki-67 labeling that extended well beyond the superficial mucosa. In addition, while superficial signet ring cancer exhibited decreased or absent E-cadherin and beta-catenin protein expression in all cases studied, deeply invasive signet ring cancer showed reversion to E-cadherin and beta-catenin protein expression in a subset of mutation carriers. Our study indicates that superficial intramucosal signet ring carcinoma, although widespread, is predominantly located in the proximal one third of the stomach in patients with E-cadherin gene mutations. The observed site predilection suggests a possible role for geographically targeted endoscopic surveillance biopsy in patients who elect to delay surgical intervention.