Richard A. Komorowski

Cystic pancreatic neoplasms: observe or operate.

Objective:The objectives of this analysis were to define the incidence, natural history, and predictors of neoplasia in pancreatic cysts to determine which patients can safely be observed and which should undergo an operation. Summary Background Data:With advancements in imaging technology, cystic lesions of the pancreas are being detected with increased frequency. Many of these lesions are small and asymptomatic, but they may be associated with pancreatitis or have malignant potential. Therefore, the management of these patients is complex, and knowledge of pancreatic cyst natural history and predictors of neoplasia are important. Methods:From January 1995 through December 2002, all radiologic, surgical, and pathology records were reviewed for the presence of pancreatic cysts. In determining natural history, only patients with 2 scans more than 1 month apart at our institution were included. Patients with a clinical history and laboratory evidence of pancreatitis and/or pathologic confirmation of a pseudocyst were excluded. Factors analyzed as potential predictors of neoplasia included age, gender, cyst size, and symptoms. Serous cystadenomas, solid and cystic papillary (Hamoudi) tumors, lymphoepithelial cysts and simple cysts were all benign, whereas mucinous cystic neoplasms, intraductal papillary mucinous neoplasm, cystic neuroendocrine tumors, and cystadenocarcinomas were considered to be premalignant or malignant. Results:Among 24,039 CT or MR scans, 290 patients (1.2%) had pancreatic cysts, and 168 of these patients (0.7%) had no documentation of pancreatitis. Seventy-nine of these patients with 103 cysts had more than 1 scan with an average interval of 16 months. These cysts increased in size in 19%, did not change in 59% and decreased in 22% of patients. Forty-nine patients underwent surgery for 14 benign (serous cystadenomas = 10, Hamoudi = 2, lymphoepithelial = 1, simple = 1) 25 premalignant (mucinous cystic neoplasm =16, intraductal papillary mucinous neoplasm = 5, neuroendocrine tumors = 4), or 10 malignant (intraductal papillary mucinous neoplasm = 7, cystadenocarcinomas = 3) lesions. Gender and cyst size did not predict neoplasia. However, presence of symptoms predicted premalignant or malignant pathology (60% vs. 23%, P < 0.05), and age over 70 years was associated with malignancy (60% vs. 21%, P < 0.02). Conclusions:These data suggest that cystic pancreatic neoplasms 1) occur in 0.7% of patients, 2) increase in 19% over 16 months, and 3) are likely (60%) to be malignant in patients older than 70 years. Therefore, we recommend surgical excision for pancreatic cysts that are increasing under observation, symptomatic, or detected radiologically in fit older patients.

Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features

BACKGROUND Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. METHODS Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (>/=15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999-2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. RESULTS Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. CONCLUSIONS Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease.

Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation and is characterized by the overproduction of proinflammatory cytokines. In this study, we have identified interleukin-6 (IL-6) as a critical inflammatory cytokine that alters the balance between the effector and regulatory arms of the immune system and drives a proinflammatory phenotype that is a defining characteristic of GVHD. Our results demonstrate that inhibition of the IL-6 signaling pathway by way of antibody-mediated blockade of the IL-6 receptor (IL-6R) markedly reduces pathologic damage attributable to GVHD. This is accompanied by a significant increase in the absolute number of regulatory T cells (Tregs) that is due to augmentation of thymic-dependent and thymic-independent Treg production. Correspondingly, there is a significant reduction in the number of T helper 1 and T helper 17 cells in GVHD target organs, demonstrating that blockade of IL-6 signaling decreases the ratio of proinflammatory T cells to Tregs. These studies demonstrate that antibody blockade of the IL-6R serves to recalibrate the effector and regulatory arms of the immune system and represents a novel, potentially clinically translatable, strategy for the attenuation of GVHD.

Cystic pancreatic neoplasms: enucleate or resect? ☆

Asymptomatic cystic pancreatic neoplasms are being detected by abdominal imaging with increasing frequency. Enucleation of small cystic neoplasms can be performed without recurrence but has been associated with a higher incidence of pancreatic fistula. Thus the procedure has been modified to include intraoperative ultrasound imaging and closure of the pancreatic defect. This analysis was performed to determine whether these modifications have improved operative outcome. Thirty patients with mucinous cystic neoplasms (n = 16), serous cystadenomas (n = 10), and cystic islet cell tumors (n = 4) were studied. Enucleation was performed in 11 patients (7 with mucinous cystic neoplasms, 2 with serous cystadenomas and 2 with islet cell tumors), whereas 19 underwent resection of cystic tumors (pancreatoduodenectomy in 8 and distal pancreatectomy in 11). The mean groups did not differ with regard to age (57 years), gender (73% female), presentation (63% incidental), or site (43% head, neck, or uncinate). Patients undergoing enucleation had smaller tumors (2.2 vs. 4.7 cm, P < 0.01) that were less likely to be in the tail (9% vs. 42%). Operative time was significantly shorter in the enucleation group (199 vs. 298 minutes, P < 0.01). Blood loss also was significantly reduced in the enucleation group (114 vs. 450 ml, P < 0.001). Pancreatic fistula rates (27% vs. 26%) and length of hospital stay (12.6 vs. 15.7 days) were similar in the two groupsz. Enucleation of benign cystic pancreatic neoplasms reduces operative time and blood loss without increasing postoperative complications or length of stay. Therefore enucleation should be the standard operation for small benign cystic neoplasms in the uncinate, head, neck, and body of the pancreas.

Thyroglossal duct carcinoma

Primary carcinoma of the thyroglossal duct is rare. This discussion reports two cases and reviews the 50 previously reported in the literature. The criteria for diagnosis include evidence of a thyroglossal duct remnant and a normal thyroid gland. The differentiation from cystic metastases to lymph nodes is pointed out. The histologic types parallel those of carcinoma of the thyroid gland, papillary carcinoma being the most common and having a generally favorable prognosis. The clinical presentation of these tumors is similar to that with benign cysts and thus is of limited value in the diagnosis.

Unsedated transnasal endoscopy accurately detects Barrett's metaplasia and dysplasia.

BACKGROUND Unsedated transnasal upper endoscopy has a diagnostic yield comparable with that of sedated conventional upper endoscopy. The ability of transnasal upper endoscopy to detect Barretts metaplasia or dysplastic change has not been systematically evaluated. The aim of this study was to assess the feasibility of transnasal upper endoscopy for surveillance of patients with Barretts esophagus and to evaluate its histopathologic yield for Barretts metaplasia and dysplasia. METHODS Thirty-two patients with Barretts esophagus were evaluated with conventional upper endoscopy and transnasal upper endoscopy. An effort was made to recruit patients known to have dysplasia. Quadrantic biopsy specimens were taken with standard (conventional upper endoscopy) and pediatric (transnasal upper endoscopy) biopsy forceps at procedures performed at least 1 week apart. Two blinded pathologists evaluated the specimens. RESULTS Transnasal upper endoscopy detected Barretts metaplasia histopathologically in 31 of 32 patients. Level of agreement for presence of dysplasia in biopsy specimens obtained between conventional upper endoscopy and transnasal upper endoscopy was excellent (k = 0.79). Interobserver agreement for dysplasia in specimens obtained by conventional upper endoscopy (k = 0.61) and by transnasal upper endoscopy (k = 0.61) were similar. Intraobserver agreement between conventional upper endoscopy and transnasal upper endoscopy biopsy specimens for dysplasia by pathologist 1 (k = 0.73) and pathologist 2 (k = 0.75) were also similar. No significant adverse effects were noted. CONCLUSIONS Transnasal upper endoscopy is feasible and accurate for identification and histopathologic confirmation of Barretts metaplasia with a histopathologic yield for dysplasia comparable with conventional upper endoscopy.

Occult thyroid pathology in the young adult: An autopsy study of 138 patients without clinical thyroid disease

Thyroid glands from autopsies on 138 adults, ages 20 to 40 years, with no known clinical or laboratory evidence of thyroid disease, were serially sectioned at 2 mm intervals and microscopically examined for occult thyroid disease and anatomic variations. Occult papillary carcinoma was found in 3% of the glands, along with a single case of medullary carcinoma. The prevalence of occult thyroid carcinoma in this group of young adults is significantly less than that reported in the literature in people over forty (P less than .001). The glands demonstrated a number of other morphologic changes of importance to surgical pathologists. The thyroid capsule was incomplete in 62% of the glands. Thyroid follicles were found in the capsule in 14% of cases and thyroid follicles or nodules were outside the gland in perithyroid connective tissue in 88% of cases. Thyroid follicles were identified in 7% of cases in perithyroid strap muscles attached to the pyramidal lobe. A number of other, less common anatomic variations were also seen.

Cystic pancreatic neuroendocrine tumors: Is preoperative diagnosis possible?

Pancreatic neuroendocrine tumors rarely undergo cystic degeneration leading to a radiologic appearance, which is often interpreted as a pancreatic mucinous cystadenoma or pseudocyst. We reviewed our experience with 38 neuroendocrine tumors, four of which were cystic, and 24 other cystic pancreatic tumors (mucinous cystadenoma [n = 5], cystadenocarcinoma [n = 6], serous cystadenoma [n = 3], solid/cystic papillary neoplasm [n = 3], intraductal papillary mucinous tumor [n = 6], and mucinous adenocarcinoma [n = 1]) managed operatively between 1990 and 2000. This review was undertaken to identify clinical and pathologic features useful for preoperative diagnosis of cystic neuroendocrine tumors. Two of the four patients with cystic neuroendocrine tumors presented with abdominal pain, one patient was asymptomatic, and one patient had hypoglycemia. Three of the four cystic neuroendocrine tumors were identified by CT scan, and none were biopsied preoperatively. Preoperative diagnoses included mucinous cystadenoma in two patients (n = 2), pancreatic cystic neoplasm in one patient, (n = 1) and insulinoma in one patient (n = 1). All four cystic neuroendocrine tumors were benign and were completely resected (distal pancreatectomy [n = 2], enucleation [n = 2]). Cystic neuroendocrine tumors are difficult to diagnose preoperatively because the majority of these tumors are nonfunctional, and CT does not differentiate these tumors from other cystic neoplasms. Cystic neuroendocrine tumors represent a subgroup of pancreatic cystic and neuroendocrine tumors with malignant potential. Their high resectability rate further supports the role of surgical exploration and resection in the treatment of pancreatic cystic neoplasms.

Histologic spectrum of diversion colitis

Biopsy specimens taken from six patients with diversion colitis, an inflammatory process that occurs in the bypassed colonic segment after diversion of the fecal stream, showed a spectrum of histologic changes ranging from mild colitis to those seen in severe active chronic ulcerative colitis. Histologic abnormalities included aphthous ulcers, crypt distortion, atrophy and abscesses, a villous colonic surface, and a mixed acute and chronic inflammatory infiltrate with patchy lymphoid hyperplasia. Accurate pathologic diagnosis is dependent on clinical history, comparison of histologic morphology in both colonic segments, and response to therapy with local application of short chain fatty acids.

Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: Higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45

Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2–7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin–eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.