Deborah Giusto

Tumor scatter after neoadjuvant therapy for rectal cancer: are we dealing with an invisible margin?

BACKGROUND: After the impressive response of rectal cancers to neoadjuvant therapy, it seems reasonable to ask: can we can excise the small ulcer locally or avoid a radical resection if there is no gross residual tumor? Does gross response reflect what happens to tumor cells microscopically after radiation? OBJECTIVE: The aim of this study was to identify microscopic tumor cell response to radiation. DESIGN: This study is a retrospective review of a prospectively collected database. SETTING: This investigation was conducted at a single tertiary medical center. PATIENTS: Patients were selected who had elective radical resection for rectal cancer after preoperative chemotherapy and radiation performed by 2 colorectal surgeons between 2006 and 2011. MAIN OUTCOME MEASURES: The primary outcome measured was tumor presence after radiation therapy RESULTS: Of the 75 patients, 20 patients were complete responders and 55 had residual cancer. Of these patients, 28 had no tumor cells seen outside the gross ulcer, and 27 (49.1%) had tumor outside the visible ulcer or microscopic tumor present with no overlying ulcer. Of these tumors, 81.5% were skewed away from the ulcer center. The mean distance of distal scatter was 1.0 cm from the visible ulcer edge to a maximum of 3 cm; 3 patients had tumor cells more than 2 cm distal to the visible ulcer edge. Tumor scatter outside the ulcer was not associated with poor prognostic factors, such as nodal and distant disease, perineural invasion, or mucin; however, it was associated with lymphovascular invasion (&khgr;2 = 4.12, p = 0.038) LIMITATIONS: There was limited access to clinical information gathered outside our institution. CONCLUSIONS: Our study suggests that 1) after radiation, the gross ulcer cannot be used to determine the sole area of potential residual tumor, 2) cancer cells may be found up to 3 cm distally from the gross ulcer, so the traditional 2-cm margin may not be adequate, and 3) local excision of the ulcer or no excision after apparent complete response appears to be insufficient treatment for rectal cancer.

Pseudomelanosis duodeni: associated with multiple clinical conditions and unpredictable iron stainability - a case series.

Pseudomelanosis duodeni is seen endoscopically as dark spots in the duodenal mucosa and is generally considered to be local deposition of iron from oral iron intake. However, pseudomelanosis duodeni may be identified histologically even before it becomes endoscopically evident; iron stainability within the mucosa is uneven and unpredictable, and multiple clinical conditions other than oral iron intake may be associated. We reviewed 17 adult patients with histologically detected pseudomelanosis duodeni, their endoscopic appearances, iron stainability, and clinical findings including oral iron and drug intake. Only 6/17 (35 %) had endoscopically apparent dark spots. Perls iron stain was entirely positive in 18 %, partially positive in 64 %, and negative in 18 % of cases. History of oral iron was present in 76 % of patients, but other clinical conditions consistently associated were hypertension in 88 %, end stage renal disease in 59 %, and diabetes mellitus in 35 % of patients.

Diffuse cirrhosis-like hepatocellular carcinoma: a clinically and radiographically undetected variant mimicking cirrhosis.

A rare variant of hepatocellular carcinoma (HCC) is encountered that produces small cirrhosis-like nodules diffusely throughout the liver (CL-HCC), instead of a larger evident mass. This pattern remains undetected as carcinoma clinically and radiographically and is unexpectedly discovered after liver transplantation in the explanted native liver. We studied 10 such cases (9 males and 1 female, age 35 to 80 y) from 4 medical centers. The pretransplant clinical, laboratory, and radiographical studies were reviewed to determine the cause and stage of liver disease, α-fetoprotein (AFP) levels, and detectability of a mass on imaging. All 10 cases had underlying cirrhosis of varying etiology [3 hepatitis C virus (HCV), 3 alcoholic hepatitis, 1 hepatitis B virus, 1 autoimmune, and 2 mixed HCV/alcoholic hepatitis and hemochromatosis/HCV] and underwent orthotopic liver transplantation with no preoperative clinical suspicion of HCC. Ultrasound and/or dynamic imaging showed cirrhosis and no definite HCC. AFP levels were only mildly elevated in only 3 of 10 cases (144, 150, and 252 ng/mL). Grossly, there were innumerable (from about 20 to >1000) small CL-HCC nodules (0.2 to 0.6 cm) scattered among cirrhotic nodules. Histologically, these were well or moderately differentiated HCC, often with pseudoglandular pattern, perinodular sclerotic rims, cholestasis, frequent Mallory bodies, and small vessel invasion. In addition to the usual HCC immunophenotype, CL-HCC showed frequent ubiquitin and cytoplasmic and membranous CD10 positivity, relatively low Ki-67 proliferative index and absence of AFP immunohistochemically. CL-HCC warrants recognition as a unique HCC variant that evades pretransplant detection despite massive tumor burden, mimics cirrhotic nodules, and shows some uncommon pathologic and immunophenotypical characteristics.

Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus.

Current guidelines for endoscopic surveillance of Barretts esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.

Transjugular Liver Biopsy: Comparison of Sample Adequacy with the Use of Two Automated Needle Systems

PURPOSE To compare the adequacy of transjugular liver biopsy (TJLB) specimens with use of the 18-gauge Quick-Core and Flexcore needles. MATERIALS AND METHODS The records of 233 patients who underwent a TJLB procedure from January 2005 to December 2006 were retrospectively reviewed. Tissue samples from a total of 194 procedures were available for review; 117 TJLB procedures were performed with a Quick-Core needle and 77 were performed with a Flexcore needle. A single pathologist reviewed all the liver biopsy specimens in a blinded fashion. The χ(2), Fisher exact, and Student t tests were used to analyze differences between groups. RESULTS The TJLB procedure was technically successful in 232 of 233 cases (99.6%). Histologic diagnosis was possible in 96% of cases. Sample fragmentation rates were 24.9% with the Quick-Core needle and 14.3% with the Flexcore needle (P = .1). The mean numbers of complete portal tracts (CPTs) per submitted tissue per procedure were 10.0 ± 4.6 for the Quick-Core needle and 12.2 ± 6.1 for the Flexcore needle (P = .003). The mean numbers of CPTs per liver sample were 2.63 ± 1.8 for the Quick-Core needle and 3.28 ± 3.3 for the Flexcore needle (P = .00004). Complications were more common in patients with multiple comorbidities such as renal failure and coagulopathy and those who had received a liver transplant. CONCLUSIONS This study demonstrates that the 18-gauge Flexcore TJLB system provided better liver biopsy specimens compared with the 18-gauge Quick-Core needle system.

Histopathology predictors of medically refractory ulcerative colitis.

PURPOSE: The ability of ulcerative colitis histology to predict medically refractory disease was evaluated. METHODS: Twenty patients who underwent colectomy for medically refractory disease were compared with 48 medically managed patients. All patients were followed up for ≥6 months. The study design was a retrospective longitudinal observational chart review to determine whether specific histologic parameters were predictive of a later colectomy for medically refractory disease. RESULTS: On initial biopsy, medically refractory patients were more likely to have severe cryptitis, 75% vs 49%; lymphoid follicles, 78% vs 48%; and erosions, 35% vs 11%. There was no significant difference in the prevalence of crypt abscesses, mucin depletion, crypt distortion, or mucosal ulceration between medically refractory and medically managed patients. Active inflammation on endoscopy was not statistically different between groups (P = .192). In a recursive partition model, the strongest predictors of future colectomy were age dependent. Among older patients (>38 y), severe cryptitis was the strongest determinant of refractory disease. Only 1 of 21 (5%) of the patients who initially did not have severe cryptitis progressed to colectomy. In younger patients (≤38 y), the presence of lymphoid follicles was the strongest predictor of future colectomy; 9 of 14 (64%) patients with lymphoid follicles progressed to colectomy. CONCLUSIONS: Medically refractory ulcerative colitis was associated with initial biopsy findings of severe cryptitis, lymphoid follicles, and erosions. Refractory disease was not predicted by the severity or extent of endoscopic findings. In younger patients, the presence of lymphoid follicles, and in older patients, severe cryptitis, were the most important predictors of medically refractory disease.

A Man with a Chronic Painful Perianal Ulcer

Diagnosis: Perianal amebiasis cutis (Entamoeba histolytica). Examination of biopsy specimens from the perianal ulcer revealed the presence of invasive E. histolytica (figures 1-3). Concurrent colonoscopy findings and examination of rectal biopsy specimens also showed focal proctitis with invasive amebic parasites. No pathologic evidence of Crohn disease or ulcerative colitis was seen. Tests for HIV, Neisseria gonorrhea, Chlamydia trachomatis (including lymphogranuloma venereum serovars), Treponema pallidum, and Herpes simplexhad negative results. The patients ulcer and symptoms rapidly resolved with a 2-week course of metronidazole. Because the patient was lost to follow-up, he did not receive paromomycin at the end of

Pathology of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. HCC is intriguing at multiple levels including its remarkable geographic variation, strong etiological association with hepatitis viral infections, certain carcinogens and metabolic diseases, preference for males, and predisposition to develop in cirrhosis or chronic liver injury from any cause [1]. HCC developing in the setting of cirrhosis is far more common in low incidence regions such as North America (as many as 90% of patients may be cirrhotic) than in high incidence regions such as Eastern Asia and Africa (only about 50% of patients may be cirrhotic), where hepatitis B virus is the most common cause of chronic liver disease [2]. Differences in geographical and age incidences are linked to variations in associated risk factors: HCV, HBV (+/− HDV), EtOH, aflatoxin B1, tobacco, NAFLD, hemochromatosis, tyrosinemia, alpha-1-antitrypsin deficiency, etc. These varied etiological factors also contribute toward complex and heterogeneous molecular genetic cellular changes and pathways during hepatocarcinogenesis. It is quite rare for HCC, except the fibrolamellar variant, to occur in patients who have no underlying liver disease at all.