Pre-resection Biopsies Research Articles

Endoscopic submucosal dissection and JNET classification for colorectal neoplasia: A North American academic center experience.

Endoscopic submucosal dissection (ESD) enables minimally invasive resection of superficial gastrointestinal neoplasms en bloc regardless of size. The Japan narrow band imaging expert team (JNET) classification utilizes optical magnification and narrow band imaging (NBI) to predict pathology. In North America, ESD is far from ubiquitous, and regional outcomes are not widely described. To date there are no North American studies describing the application and yield of the JNET classification as applied in the practice of ESD. A retrospective, single-center, cohort analysis was performed on a prospectively maintained database of ESD procedures. Between July 2016 and February 2023, all consecutive patients treated with ESD for colorectal lesions were identified and stratified by lesion location, JNET, NBI International Colorectal Endoscopic, lateral spreading tumors, and Paris classifications. Univariate analysis was used for clinicopathological data. p<0.05 was considered statistically significant. A total of 112 patients were identified. One lesion, a lipoma, was excluded. Overall, 49.5% (55/111) of lesions were colonic and 50.5% (56/111) rectal. Most lesions were lateral spreading tumors (60.4%, 67/111). Overall, 96.4% (107/111) ESDs were successfully completed, 98.1% (105/107) en bloc, and 87.9% (94/107) R0. Adverse events occurred in 1.8% (2/111) of procedures. The median diameter was 4.0cm and resected in a median time of 62.0min. Overall, 70.1% (47/67) lesions were upstaged from pre-ESD biopsy. JNET 2B showed 80.2% (95% CI 71.5-87.1) accuracy for high-grade dysplasia or sm1. All JNET type 3 were ≥sm2 (p<0.001). ESD permits safe and effective resection of superficial colorectal neoplasms. JNET classification was more accurate than pre-resection biopsy at predicting histology in this series.

Comments on: "Effect of pre-resection biopsy on detection of advanced dysplasia in large nonpedunculated colorectal polyps undergoing endoscopic mucosal resection".

Comments on: "Effect of pre-resection biopsy on detection of advanced dysplasia in large nonpedunculated colorectal polyps undergoing endoscopic mucosal resection".

Effect of pre-resection biopsy on detection of advanced dysplasia in large nonpedunculated colorectal polyps undergoing endoscopic mucosal resection.

BACKGROUND : Pre-resection biopsy (PRB) of large nonpedunculated colorectal polyps (LNPCPs, ≥ 20 mm) is often performed before referral for endoscopic mucosal resection (EMR). How this affects the EMR procedure is unknown. METHODS : This was a retrospective analysis of a prospectively collected cohort of patients with LNPCPs referred for EMR between 2013 to 2016 at an Australian tertiary center. Outcomes were differences between PRB and EMR histology, and effects of PRB on the EMR procedure. RESULTS: Among 586 LNPCPs, lesions that underwent PRB were larger (median 35 vs. 30 mm; P < 0.007), and more commonly morphologically flat or slightly elevated (P = 0.01) compared with lesions without PRB. PRB histology was upstaged in 26.1 %, downstaged in 13.8 %, and unchanged in 60.1 % after EMR. Sensitivity of PRB was 77.2 % (95 %CI 71.1-82.4) for low grade dysplasia (LGD) and 21.2 % (95 %CI 11.5-35.1) for high grade dysplasia (HGD). Where EMR specimen showed HGD, PRB had detected LGD in 76.9 %. Where EMR specimen showed cancer, PRB had detected dysplasia only. PRB was associated with more submucosal fibrosis (P = 0.001) and intraprocedural bleeding (P = 0.03). EMR success or recurrence was not affected. CONCLUSIONS: Routine PRB of LNPCP did not reliably detect advanced histology and may have affected EMR complexity. PRB should be utilized with caution in guiding endoscopic management of LNPCPs.

SOX9 and SATB2 immunohistochemistry cannot reliably distinguish between osteosarcoma and chondrosarcoma on biopsy material

Limited tissue in biopsies of malignant bone lesions can preclude definitive subclassification, especially when cellular or matrix elements are sparse, absent, or confounding. It is uncertain whether immunohistochemistry for SOX9 (marker of chondrogenesis) and SATB2 (marker of osteoblastic differentiation) may be discriminatory tools towardosteosarcoma and chondrosarcoma. This study interrogated the preresection biopsies of a cohort of osteosarcoma and chondrosarcoma with SATB2 and SOX9 in tandem, to assess their value as diagnostic adjuncts as well as their concordance with the final resection diagnoses. SATB2 was expressed more frequently in osteosarcoma (46/53, 86%) than in chondrosarcoma (9/18, 50%); SOX9 was expressed in high frequencies in both osteosarcoma (52/53, 98%) and chondrosarcoma (17/18, 94%), and SATB2 and SOX9 were coexpressed in both osteosarcoma (46/53, 89%) and chondrosarcoma (8/18, 44%). There exists significant overlap in the expression of SATB2 and SOX9 in osteosarcoma and chondrosarcoma. These markers are not expressed in a distribution that is unique enough for application towardthis particular diagnostic differential.

A138 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR BARRETT’S NEOPLASIA IN A NORTH AMERICAN ACADEMIC CENTRE

Abstract Background Endoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of Barrett’s associated neoplastic lesions. Though endoscopic therapy is classically performed with endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA), ESD provides the advantage of en-bloc resections, and greater R0 resection rates, which are defined as negative deep and lateral margins on histology. Aims Our aim is to present procedural outcomes and subgroup analysis from one of the largest single centre cohorts of esophageal ESD in North America, and the first from Canada. Methods All patients undergoing esophageal ESD for Barrett’s neoplasia between Oct 2016 and June 2020 at a single tertiary care centre in Canada were included in the cohort. Demographic, procedural data and lesion characteristics are presented. Subgroup analysis was performed on patients who underwent extensive resection (≥75% of esophageal circumference) and patients who developed strictures. Statistical analysis included chi square testing on categorical variables and unpaired t-test for continuous variables. Binomial univariable logistic regression was performed to investigate factors associated with stricture formation. Results Thirty-four patients underwent esophageal ESD for Barrett’s associated neoplasia during the study period. The median lesion diameter was 5.7 cm (IQR 4.2 -7.5) and median procedure time 129 min (IQR 66–200). The en-bloc resection rate was 97%, and the R0 resection rate was 91%. Curative resection was achieved in 82% of patients. Upstaging from the pre-resection biopsy to post-ESD histology occurred in 59% of cases. Two adverse events occurred (1 delayed bleed, 1 aspiration event). There were no perforations. Procedural outcomes were similar between patients with extensive resections, but patients with ≥75% circumferential resection developed more strictures (65% vs 13%, p=0.001). Stricture formation was associated with extensive resection (OR 15.4, 95%CI[2.50 - 95.01]) and longer lesion diameter (OR 1.73, 95%CI [1.11 - 2.70]). Conclusions Our experience with ESD for Barrett’s related neoplasia shows excellent en-bloc and R0 resection rate, and provides more accurate histological specimens. Curative resection is possible in the vast majority of cases, including those with extensive resections. Further investigation into stricture prophylaxis will be useful as larger resections are attempted. Funding Agencies None

Safety of Endoscopic Snare Ampullectomy for Adenomatous Ampullary Lesions: Focus on Pancreatic Stent Placement to Prevent Pancreatitis.

Ampullary tumors, although relatively uncommon, are increasingly diagnosed due to ongoing progress in imaging technology and the diagnostic accuracy of endoscopic ultrasound and magnetic resonance cholangiopancreatography. Endoscopic ampullectomy (EA) has become the preferred treatment option over surgery due to its lower morbidity for benign ampullary adenomas. This study aims to evaluate the efficacy, safety, and outcome of EA in 30 patients with benign-appearing ampullary lesions with particular emphasis on the accuracy of preampullectomy histology and technical details of the pancreatic duct drainage to prevent postprocedural pancreatitis. Data from a cohort of 30 patients who underwent EA were retrospectively analyzed. Histologic characteristics of the ampullomas, accuracy of histology of pre-EA biopsy specimen, safety of the procedure, recurrence rate, as well as the clinical outcome of all patients, are analyzed and discussed. Endoscopic resection was successful as a definitive treatment in 25 patients (83.3%). Five patients required additional surgery. In 8 patients, a definitive histologic specimen revealed an adenocarcinoma (3 in situ and 5 invasive). The diagnostic accuracy obtained by preresection biopsy specimen was low (0.70). Pancreatic duct stent placement after snare resection was unsuccessful in 9 patients, and 3 of them developed pancreatitis after EA. EA appears to be a relatively safe alternative to surgery as the first therapeutic option for selected patients with benign-appearing ampullary adenomas. A correct preoperative evaluation by endoscopic ultrasound and magnetic resonance cholangiopancreatography can help to define the anatomy of the pancreatic duct to improve the success rate of pancreatic stent placement which seems to offer a protective role in the prevention of postprocedural pancreatitis.

Idiopathic myointimal hyperplasia is a distinct cause of chronic colon ischaemia.

Colon ischaemia (CI) is most commonly an acute and reversible manifestation of a transient, non-occlusive decrease of blood flow in the colonic microvasculature. Irreversible complications are uncommon and the progression to chronic CI remains controversial. Our objective was to identify cases of chronic CI and assess for distinct clinicopathological features. A retrospective review was performed of CI patients having symptom chronicity of ≥1month and ischaemic histology at our institution from 1994 to 2015. Demographic, clinical, endoscopic, radiological, pathological and outcome variables were abstracted. Histological evaluation was performed by two gastrointestinal pathologists. Fifteen patients (n=9; 67% men) with a median age of 65years (range 22-88) were identified. The most common presenting symptoms were diarrhoea and abdominal pain (n=6, 86%; n=5, 71%, respectively). The typical endoscopic appearance was segmental ulceration of the sigmoid colon (n=6, 75%). Vascular imaging showed patent mesenteric vessels in all patients. Histopathological evaluation revealed venous intimal hyperplasia consistent with idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) in eight patients; the remainder showed non-specific ulceration and fibrosis. Surgical resection was performed in seven IMHMV patients, resulting in symptom resolution. On re-review of pre-resection biopsies, all IMHMV patients had characteristic changes of hyperplastic, thick-walled, hyalinized vessels in the lamina propria. IMHMV is a unique histopathological entity causing chronic CI. The small vessel histological changes in IMHMV are distinctive in colonic resections and undetectable by routine vascular imaging. Preoperative diagnosis of IMHMV is possible with endoscopic biopsy and segmental colon resection is curative.

Probe confocal laser endomicroscopy in the therapeutic endoscopic management of Barrett's dysplasia.

BackgroundEndoscopic management of Barrett’s esophagus (BE) depends on the histological stage of BE and includes the following: follow up, endotherapy with thermal ablation, and piecemeal or monobloc endoscopic resection (ER). We know that biopsies are unreliable in 20-75% of cases. The aim of our study was to evaluate the efficiency of probe confocal laser endomicroscopy (pCLE) in the diagnosis of the histological stage of BE, compared with the final histological results after ER.MethodsThis retrospective study was based on a prospective registry of patients referred for management of BE-associated dysplasia. The inclusion criteria were dysplasia associated with BE on pre-resection biopsy and endoscopic resection of the examined areas. CLE examinations (pCLEs) were performed using the Gastroflex® probe (Maunakea company). ER was sufficient to ensure that the target area was resected. The following four potential diagnoses were considered: normal or inflammatory mucosa, metaplasia (BE), low-grade dysplasia (LGD), and high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC).ResultsThe sensitivity, specificity, and accuracy in the detection of HGD/EAC were 92.9%, 71.4% and 80% for pCLE, and 78.6%, 61.9%, and 68.6% for histological biopsy, respectively. The differences in favor of pCLE were not statistically significant (P=0.2); however, in 13 patients with irregularities of the mucosa without elevated or depressed lesions (2 HGD/EAC and 11 non-HGD/EAC), pCLE led to positive redirection of therapy in 70% (9/13) of cases.ConclusionIn the absence of visible lesions, pCLE appears to lead to correct diagnoses and to aid real-time decisions regarding therapeutic management.

Idiopathic Myointimal Hyperplasia Is a Distinct Cause of Chronic Colon Ischemia

Introduction: Colon ischemia (CI) is typically an acute manifestation of altered colonic blood flow resulting in mucosal ischemia and resolves spontaneously within days. Some patients, however, may evolve into chronic segmental colitis. This is a controversial topic, given the varied definitions of this entity and lack of distinguishing histologic features. We sought to further examine the clinicopathologic features of chronic CI in an attempt to distinguish it from acute CI. Methods: Cases were identified from our electronic medical record between 1/1/94 and 8/15/15. Only cases having symptom chronicity (>1 month of abdominal symptoms) and persistent ischemic histology in patients 18-99 years of age were included for review. Histologic evaluation was performed by two gastrointestinal pathologists. Results: From 15 CI patients with clinical and histologic chronicity, 8 had unequivocal venous intimal hyperplasia characterized by thickened submucosal, mural and extramural veins which defines the rare condition known as idiopathic myointimal hyperplasia of mesenteric veins (IMHMV). The remaining 7 patients had non-specific histologic findings of ischemia. The median age at diagnosis for patients with IMHMV was 62.5 years (range 22-75) compared to 61.6 years (range 29-88) in those without. By sex, 2 of the IMHMV and 3 non-IMHMV patients were female. Vascular imaging in all IMHMV cases demonstrated mesenteric arterial and venous patency. Abdominal pain and diarrhea were the two most common presenting symptoms, occurring in 7 (87.5%) and 5 (62.5%) cases, respectively. The sigmoid colon was most commonly involved in 75% of IMHMV versus only 29% of non-IMHMV cases. Surgical resection was performed in 7 IMHMV patients as part of management for CI or suspected inflammatory bowel disease, resulting in symptomatic resolution. In retrospect, all 7 IMHMV patients with resection had characteristic changes in pre-resection biopsies, including thickened, tortuous mucosal venules and, in some cases, myointimal hyperplasia in superficial submucosal veins. Conclusion: The histologic changes of IMHMV are distinctive in colonic resections and are not detected by vascular imaging. Pre-operative diagnosis of IMHMV is possible from endoscopically obtained biopsies, which show a combination ischemic injury and altered mucosal venules. As segmental colon resection is curative of IMHMV, improved awareness of this entity is needed to avoid misdiagnosis and potentially harmful treatment such as immunosuppression.

Neoplastic Barrett's oesophagus and long-term follow-up after endoscopic therapy: complete histological eradication of Barrett associated with high-grade dysplasia significantly decreases neoplasia relapse.

Endotherapy (ET) has replaced surgery as the first-line treatment of high-grade dysplasia (HGD)/superficial ECA (ECAs) from Barrett's oesophagus (BO). However, long-term follow-up and predictive factors of relapse are not so well studied. The aim of the following study was to evaluate the efficiency of ET for treatment of HGD/ECAs and to determine factors of long-term efficiency. ET procedures were manually reported and registered in a hospital data base from March 2000 to July 2010. Inclusion criteria were HGD/ECA on pre-resection biopsies, complete histological and sufficient oncological resection of HGD/ECAs, and complete macroscopic resection of metaplastic BO. Sixty patients (53 men, mean age=65years) were included. Median follow-up was 66months [range 42-80]. Complete eradication of residual histological metaplastic BO occurred in 29 patients (48%). Relapse rate at 36months was 16.6% (n=10) and was unchanged at 60months of follow-up. There was only one relapse (3.4%) in case of complete eradication of metaplastic BO and 9 (31%) in case of incomplete eradication. In univaried and multi-varied analysis, complete eradication of metaplastic BO (p<0.05) and BO length <5cm (p<0.05) were predictive of neoplastic BO non relapse. The length of BO remained a prognostic factor for disease-free survival (DFS). When these preponderant data were cancelled out in multi-varied analysis, complete eradication of BO was a prognostic factor for DFS (p<0.05). Complete histological eradication of BO by ET significantly decreases the rate of neoplasia relapse.

Prediction of Adenocarcinoma in Esophagectomy Specimens Based Upon Analysis of Preresection Biopsies of Barrett Esophagus With At Least High-Grade Dysplasia

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.

Predictive factors for histological discrepancy between endoscopic biopsies and endoscopic mucosal resection specimens in Barrett's dysplasia/early neoplasia

Introduction Accurate diagnosis of high grade dysplasia (HGD) or early cancer (EC) is of paramount importance in the management of Barrett9s oesophagus. Endoscopic biopsies are the standard method for the diagnosis of HGD/EC but discrepancies have been reported between biopsies and endoscopic mucosal resection (EMR) specimens. The aim of this study was to investigate the predictive factors for histological discrepancy between endoscopic biopsies and EMR specimens. Methods Prospectively collected data on all EMRs performed for Barrett9s HGD or EC in our institution over a 4-year period were analyzed. Histology of pre-resection biopsies and EMR specimens was retrieved from pathology records. Cases with diagnostic discrepancies between biopsies and EMRs were compared with those without discrepancies. Multivariate linear regression analysis was used with size of lesion, endoscopic morphology, length of Barrett9s, number of targeted biopsies, age and sex of patients as predictive factors. Results 59 lesions from 57 patients (43 men, mean age: 67 ± 11.2) who underwent EMR were studied. Mean length of Barrett9s was 5.2 ± 3.4 cm (range 1–13) and the mean size of lesions was 15.5 ± 4.9 mm (range 7–30 mm). Elevated (Paris 0-Is or 0-IIa) lesions were observed in 31 (52.5%) and flat/depressed lesions (0-IIb or 0-IIc) in 28 (47.5%) of cases. The mean number of pre-resection targeted biopsies was 3.1 ± 1.01 (range 1–5). The ‘band and snare’ mucosectomy technique was used in 46 (78%) and the cap-assisted technique in 13 (22%) EMR cases. Post-EMR histological diagnosis was HGD in 22 (37.3%) and carcinoma in 37 (62.7%) cases. The histological discrepancy rate was 44% (26/59). EMR upgraded the histological diagnosis in 22 (37.3%) cases and downgraded it in 4 (6.8%) resections. On multivariate linear regression analysis, Conclusion Obtaining 3 or more targeted biopsies per lesion improves the histological correlation between endoscopic biopsies and EMR specimens in patients with Barrett9s early neoplasia.

Rectal Sparing and Skip Lesions in Ulcerative Colitis: A Comparative Study of Endoscopic and Histologic Findings in Patients Who Underwent Proctocolectomy

Ulcerative colitis (UC) is generally considered an inflammatory disorder that always involves the rectum and may also involve more proximal portions of the colon, but always in a diffuse and continuous (non-segmental) fashion. Earlier biopsy studies have shown that both rectal sparing and patchy disease may occur during the natural history of UC and may, in fact, be accentuated by oral or enema therapy; but these features have never been evaluated in resection specimens. The purpose of this study was to evaluate the prevalence rates and degree of endoscopic and histologic patchiness of disease and rectal sparing in preoperative endoscopic biopsies and to compare the findings with those observed in colectomy specimens. In addition, we evaluated the effects of immunomodulators and anti-TNF-alpha therapy on normalization of mucosa. Cases of 56 UC patients, all of whom had at least 1 preoperative endoscopy with biopsies, and who subsequently underwent a colectomy for nonneoplastic complications, were collected and reviewed for a variety of inflammatory histologic features, such as patchiness of disease and rectal sparing. Both of these features were categorized as either absolute or relative according to predetermined criteria. All biopsies and resection specimens were graded for their inflammatory activity on a 5-point scale. An independent score was provided for each portion of the colon, and a mean colitis score of the entire colon was calculated by adding all inflammatory grades for each colonic segment and dividing this number by the number of segments. Endoscopic, biopsy, and resection specimen findings were correlated with each other and with clinical and demographic features, such as duration of colitis, extent of colitis, and types of medications used for at least 6 months before resection. Overall, the mean colitis score in biopsies was significantly lower than in resection specimens (2.7+/-0.9 vs. 3.2+/-0.8, P<0.01). Evidence of rectal sparing and patchy disease occurred in 32.1% and 30.4% of patients by endoscopy, and 30.4% and 25% of patients by analysis of biopsies. Only 3 patients (5.4%) showed rectal sparing, and all of these were considered "relative" after evaluation of the patients' colectomy specimens. Six (10.7%) showed patchiness of disease in the colon resection specimen, 4 of which were absolute. After evaluation of all of the patients' preresection biopsy specimens and colectomy specimens, none of the patients (0%) showed complete absence of rectal involvement (absolute rectal sparing) after all of the tissue sections were evaluated. A significant correlation was noted between endoscopic and biopsy findings and between biopsy and colectomy findings, but poor correlation was noted between the patients' endoscopic features and the pathologic features in the patients' colectomy specimens. No correlation was noted between any specific type or combination of medication use and the presence or frequency of rectal sparing or patchiness of disease. These data indicate that absolute rectal sparing does not occur in UC patients even after long-term use of antiinflammatory medications. The presence of 1 (or more) tissue sections from an IBD patient's colectomy specimen showing complete absence of histologic features of chronicity or activity, but bordered on both sides by chronic or chronic active disease, should not represent a reason to change the patient's diagnosis from UC to Crohn disease.

Poor Interobserver Agreement in the Distinction of High-Grade Dysplasia and Adenocarcinoma in Pretreatment Barrett's Esophagus Biopsies

Grading Barrett's dysplasia at the lower end of the metaplasia-dysplasia spectrum (negative, indefinite, and low-grade dysplasia) suffers from poor interobserver agreement, even among gastrointestinal pathologists. Data evaluating interobserver agreement in Barrett's mucosal biopsies with changes at the upper end of the dysplasia spectrum (high-grade dysplasia, intramucosal, and submucosal adenocarcinoma) have not been published. The accurate categorization of pretreatment biopsies drives therapeutic decision making, but if the diagnostic distinction between cancer and high-grade dysplasia in Barrett's biopsies is inconsistent, then the use of these diagnoses to make management decisions is suspect. To this end, our aim was to assess interobserver reproducibility among a group of gastrointestinal pathologists in the interpretation of preresection biopsies. All study pathologists agreed upon the histologic criteria distinguishing four diagnostic categories, including high-grade dysplasia; high-grade dysplasia with marked distortion of glandular architecture, cannot exclude intramucosal adenocarcinoma; intramucosal adenocarcinoma; and submucosally invasive adenocarcinoma. The histologic criteria were used to independently review preresection biopsies from 163 consecutive Barrett's esophagus patients with at least high-grade dysplasia who ultimately underwent esophagectomy. Reviewers recorded the specific histologic criteria used to categorize each case and Kappa statistics were calculated to assess interobserver agreement. Using kappa statistics, the overall agreement was only fair (kappa= 0.30). Agreement for high-grade dysplasia was moderate (kappa= 0.47), while agreement for high-grade dysplasia with marked architectural distortion, cannot exclude intramucosal adenocarcinoma and intramucosal adenocarcinoma were only fair (kappa= 0.21 and 0.30, respectively) and agreement for submucosal adenocarcinoma was poor (kappa= 0.14). The overall poor interobserver reproducibility among gastrointestinal pathologists who see a high volume of Barrett's cases calls into question treatment regimens based on the assumption that high-grade dysplasia, intramucosal adenocarcinoma, and submucosal adenocarcinoma can reliably be distinguished in biopsy specimens.

New Options for the Therapy of Barrett’s High-Grade Dysplasia and Intramucosal Adenocarcinoma: Endoscopic Mucosal Resection and Ablation versus Vagal-Sparing Esophagectomy

Adenocarcinoma of the esophagus has the fastest rising incidence of any cancer in the United States and develops as a consequence of chronic gastroesophageal reflux disease [1]. Barrett’s esophagus is the precursor lesion from which adenocarcinoma develops, and surveillance programs have led to the detection of highgrade dysplasia and early-stage adenocarcinoma in an increasing number of patients. High-grade dysplasia and intramucosal adenocarcinoma, although potentially lethal, are both curable lesions in most patients [2‐4]; however, cure is dependent on complete removal of the neoplastic tissue. Until recently, this was reliably accomplished only with esophagectomy, but new technologies have been developed that allow endoscopic mucosal resection and ablation with preservation of the esophagus. The aim of this article is to explore current options for the management of Barrett’s high-grade dysplasia and intramucosal adenocarcinoma. The first fundamental issue in the treatment of highgrade dysplasia and intramucosal adenocarcinoma is to cure the patient of the disease. Patients with only highgrade dysplasia are uniformly cured with esophagectomy because invasive cancer has not developed and will not develop after removal of all of the Barrett’s mucosa. However, a number of surgical series have demonstrated that despite extensive pre-resection biopsies, in 30% to 50% of patients thought only to have high-grade dysplasia, the resected specimen will in fact have an invasive cancer [5, 6]. In the absence of a visible ulcer or nodule on endoscopy, these occult adenocarcinomas have always been limited to the mucosa in our experience [5]. In contrast, if a lesion of any sort is seen endoscopically within the columnar-lined portion of the esophagus, that lesion is at high risk to be a cancer. Further, any visible lesion that on biopsy shows adenocarcinoma cannot be assumed to be limited to the mucosa, regardless of the size or appearance of the lesion. Even very small lesions may penetrate into the submucosa, thus the endoscopic appearance of the lesion cannot be used to determine the T stage. It was hoped that endoscopic ultrasound imaging would allow accurate determination of intramucosal vs submucosal tumor invasion, but even high-frequency 20-MHz probes have not provided acceptable differentiation of these lesions [7]. The only method currently able to accurately determine the depth of invasion of a small visible lesion is endoscopic mucosal resection. This technique enables endoscopic excision of lesions sized up to 1.5 cm along with the adjacent mucosa and submucosa down to the muscularis propria and thereby allows the precise depth of invasion of the tumor to be pathologically determined. We have previously shown the accuracy of endoscopic resection as a staging procedure for early esophageal cancer, and we use it routinely for patients with a visible lesion within the Barrett’s mucosa [8].

Complications and local recurrence following lymphadenectomy

We have retrospectively reviewed the case notes of 208 patients undergoing either cervical, axillary, or inguinal lymphadenectomy with a view to determining the factors that predispose to complications and local recurrence. The most frequent complications were wound infection, seroma formation, paraesthesiae and lymphoedema. The main predisposing factor for complications was anatomical site; wound complications occur with twice the frequency in the inguinal lymphadenectomy group than in the two other sites. Preresection biopsy was also associated with an almost twofold increase in complications, while fine needle aspiration cytology was not. The two major factors influencing the incidence of local recurrence were the stage of the disease process and the use of preresection biopsy. There was a steady increase in the incidence of local recurrence with increasing stage of regional disease. In addition, local recurrence was almost twice as common in patients who had undergone biopsy before resection when compared with patients who either did not have tissue sampling before resection or had fine needle aspiration cytology alone. We conclude that fine needle aspiration cytology is safe and the investigation of choice in patients undergoing lymphadenectomy. In contrast, preresection biopsy should be avoided as it promotes both complications and local recurrence. In addition, wound complications and lymphoedema are frequent following lymphadenectomy, especially following inguinal dissection.

Controversies in the Management of Wilms' Tumor

Wilms' tumor is the most common malignant renal tumor of childhood; it represents 5% to 6% of childhood cancers in the United States. The survival rate of children with Wilms' tumor has improved dramatically, partly due to large multicenter studies conducted by the National Wilms' Tumor Study Group and the International Society of Pediatric Oncology. To ensure optimal patient outcome, the surgical management of these patients must be appropriate. Controversial issues in the management of Wilms' tumor include the value of preoperative chemotherapy; whether pre-resection biopsy is indicated and if so, how this is best performed; indications for partial nephrectomy; the treatment of lowrisk patients with surgery only; and the reliability of preoperative imaging to assess the contralateral kidney.