Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group.

Since the clinical implementation of fine needle aspiration cytology (FNAC) to diagnose thyroid carcinoma, few patients remain misdiagnosed and little is known about their clinical outcomes. An observational retrospective study was carried out to analyse prognostic factors and follow-up of patients with differentiated thyroid carcinoma (DTC) not disclosed by FNAC before surgery, compared to a control group. From October 2003 to July 2010, 308 patients underwent surgery as treatment for nodular goitre and 53 had DTC. Cases were 12 subjects with DTC and benign (n = 7) or nondiagnostic (n = 5) FNAC. Controls were 39 subjects with DTC and suspicious (n = 19) or malignant (n = 20) FNAC. Prognostic factors, recurrence and survival rates were compared. Cases had longer time from FNAC to surgery than the control group (86.8 ± 74.1 vs. 16.4 ± 23.8 weeks; P < 0.001), higher prevalence of follicular carcinoma (33.3 vs. 2.6%; P = 0.009), and of two-time total thyroidectomy (75 vs. 30.8%; P = 0.016). Average follow-up was 42.7 ± 25.3 months (2-86 months). There were no deaths. Disease-free survival for cases was 66.9 ± 5.8 months, and for controls 78.7 ± 3.9 months (P: ns). In patients with DTC, the result of the FNAC performed before surgery was not an independent predictor of recurrences or mortality in the first 7 years of follow-up. Thus, false negative or nondiagnostic FNAC in a patient with DTC does not seem to be a primary prognostic factor, but it may reveal other adverse prognostic factors such as longer time to therapy and higher prevalence of follicular carcinoma that may influence long-term outcomes.

Evolution of the incidence of collagenous colitis and lymphocytic colitis in Terrassa, Spain: a population-based study.

BACKGROUND: Previous studies suggest an increase in the incidence rate of microscopic colitis in recent decades. The aim was to evaluate changes in the population-based incidence rate of microscopic colitis and its subtypes over time in Terrassa, Spain. METHODS: This was a prospective study during the period 2004-2008, with a comparison of data from the period 1993-1997. The catchment area was a mixed rural-urban type, with nearly 290,000 inhabitants. All patients with nonbloody chronic diarrhea referred for a diagnostic colonoscopy were included. Multiple biopsy specimen samples were obtained when the macroscopic appearance of the colonic mucosa was normal to rule out microscopic colitis. Crude and adjusted incidence rates based on either the year of diagnosis or the date of onset of symptoms were calculated. RESULTS: Forty patients with collagenous colitis (CC) and 32 with lymphocytic colitis (LC) were identified. The mean annual incidence of CC and LC based on the year of onset of symptoms was 2.6/10(5) inhabitants (95% confidence interval [CI], 1.9-3.3), and 2.2/10(5) inhabitants (95% CI, 1.5-3.0), respectively. Incidence rates for CC based on the year of onset of symptoms were significantly higher in the period 2004-2008 than in 1993-1997 (2.6 versus 1.1/10(5) ; P = 0.012). The increase in CC incidence was more marked in women (P = 0.047) than in men (P = 0.19). CONCLUSIONS: The annual incidence of CC in Terrassa increased over time, mainly in women. Nevertheless, the rates were much lower than those observed in northern Europe, suggesting that there is a north-south difference in the incidence of microscopic colitis.

Paucicellular lymphocytic colitis: is it a minor form of lymphocytic colitis? A clinical pathological and immunological study.

OBJECTIVES: It has been suggested that paucicellular lymphocytic colitis (PLC) should be considered to be part of the morphological spectrum of microscopic colitis. The aim of the study was to evaluate whether PLC may be considered to be a true microscopic colitis, and in this case, whether it is a minor form of lymphocytic colitis (LC) or a different entity. METHODS: All incident cases of PLC, LC, and collagenous colitis (CC) during the period 2004-2006 were included. The incidence rate and the clinical, histopathological, and immunological features of PLC were assessed and compared with those of both LC and CC. Immunoreactivities to CD25, c-Kit, and FOXP3 in lamina propria were assessed. RESULTS: In all, 19 patients with CC, 19 with LC, and 26 with PLC were identified. CD25+FOXP3+ expression was seen only in classical forms of microscopic colitis: 12 of 19 LC, 14 of 20 CC, and none of 20 PLC cases (P < 0.0001). Diarrhea ceased in 21 of the 26 patients, with a decrease in the daily stool number from 5.08 +/- 0.44 to 1.7 +/- 0.2 (P < 0.005). The five patients with no response to therapy fulfilled the Rome II criteria of irritable bowel syndrome (IBS). CONCLUSIONS: The incidence rate of PLC, identified using objective histological criteria, was higher than those of CC and LC. The lack of expression of CD25+FOXP3+ cells in PLC, in contrast to those seen in both LC and CC, would suggest the existence of different pathophysiological mechanisms and does not support that PLC is a minor form of LC.

Lack of clinical usefulness of Das-1 monoclonal antibody and mucin expression as risk markers of gastric carcinoma in patients with gastric intestinal metaplasia.

Our aim was to evaluate the usefulness of the monoclonal antibody Das-1 as a premalignant marker of gastric intestinal metaplasia (GIM) associated with gastric cancer and its association with mucin expression. We evaluated Das-1 and mucin expression in 4 groups: 1 (n = 50), gastric carcinoma, paired samples of the cancer area and GIM away from the tumor; 2 (n = 25), gastric or duodenal ulcer with Helicobacter pylori infection with GIM and chronic gastritis; 3 (n = 25),H pylori- autoimmune chronic atrophic gastritis with GIM; and 4 (n = 25),H pylori- chronic gastritis without GIM. Das-1 immunostaining was observed in 20 (40%) of 50 cases in cancer areas. The expression of Das-1 in GIM from group 1 cases away from the cancer area was different from that in GIM from nontumor cases (groups 2 and 3): 13 (26%) of 50 vs 2 (8%) and 0 (0%) of 25 (P = .004). There was no association between Das-1 and mucin expression. Das-1 expression was associated with GIM from patients with gastric cancer. However, this relation was weaker than previously reported, precluding clinical usefulness as a premalignant marker of GIM.

Intestinal spirochetosis and chronic watery diarrhea: clinical and histological response to treatment and long-term follow up.

BACKGROUND: The clinical significance of intestinal spirochetosis is uncertain, therefore the aim of the present paper was to assess the prevalence of histological intestinal spirochetosis in patients with and without chronic watery diarrhea and to evaluate its clinical relevance. METHODS: A prospective diagnostic work-up of intestinal spirochetosis was made on biopsy samples taken from patients with chronic watery diarrhea submitted between 1994 and 2004 (1174 colonoscopies with multiple biopsies). Three other positive cases identified from routine endoscopic biopsies also were reviewed. In addition, samples from 100 asymptomatic control patients and a random sample of another 104 colonic specimens were reviewed for intestinal spirochetosis. The diagnosis was established by light and electron microscopy. Polymerase chain reaction (PCR) amplification of the 16S ribosomal RNA and reduced nicotinamide adenine dinucleotide (NADH) oxidase genes of the intestinal spirochetes Brachyspira aalborgi and Brachyspira pilosicoli was performed on tissue biopsies of the 11 positive patients. After diagnosis, treatment with penicillin benzatine (PB) or metronidazole was offered to all symptomatic patients and they were followed for a mean of 45.4 months (range: 37-113 months). RESULTS: Eight patients with chronic watery diarrhea were positive for intestinal spirochetosis. Intestinal spirochetosis was not diagnosed in the controls. Histological resolution of the infection paralleled clinical recovery in six patients (following metronidazole treatment in three). Most patients showed mild, non-specific colonic inflammation. Invasion by the spirochetes was not demonstrated by electron microscopy. Brachyspira aalborgi and B. pilosicoli each were identified by PCR in two cases. CONCLUSIONS: Histological intestinal spirochetosis appears to be relatively uncommon in Catalonia (Spain) compared to previous reports from other countries, but was identified in patients (0.7%) with chronic watery diarrhea. Sustained clinical recovery after spontaneous or drug-induced spirochetal disappearance in these individuals suggests that intestinal spirochetosis may play a pathogenic role in chronic watery diarrhea. Treatment with metronidazole is advisable in patients with persistent symptoms.

Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis.

OBJECTIVE: To assess the presence of both genetic and serological markers of coeliac disease in patients with microscopic colitis, and whether there was associated enteropathy. METHODS: HLA-DQ2, HLA-DQ8, serum immunoglobulin A-antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were investigated in 59 patients with microscopic colitis. Seventy healthy subjects acted as the control group. Endoscopic biopsies from the distal duodenum were obtained in DQ2-positive or DQ8-positive patients. Patients with histological changes compatible with gluten-sensitive enteropathy were started on a gluten-free diet. RESULTS: Seventeen of 70 (24.3%) healthy controls were DQ2-positive. Twelve of 25 (48%) patients with lymphocytic colitis (P = 0.027 versus controls), and 11 of 34 (32.3%) with collagenous colitis (P = 0.38 versus controls) were DQ2-positive. There were no differences in the frequency of DQ8-positivity. The coeliac serology was positive in one patient. Duodenal biopsies were performed in 23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III lesion) (0%; 95% confidence interval, 0-6.1). A Marsh type I lesion was found in four patients. Three of these patients were put on a gluten-free diet with disappearance of diarrhoea. CONCLUSIONS: The results suggest that there is an association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in the pathogenesis of this disease. The association of microscopic colitis with Marsh type III coeliac disease seems to be rare, making it unnecessary to routinely screen for coeliac disease in microscopic colitis patients.

Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of primary pulmonary hypertension characterized by thin-walled microvessels infiltrating the peribronchial and perivascular interstitium, the lung parenchyma, and the pleura. These proliferating microvessels are prone to bleeding, resulting in accumulation of hemosiderin-laden macrophages in alveolar spaces. Here we report 2 cases of PCH with pulmonary hypertension, 1 of them associated with mechanical intravascular hemolysis, a feature previously reported in other hemangiomatous diseases, but not in PCH. Case 2 was diagnosed by pulmonary biopsy; to our knowledge the patient is the second adult to be treated with interferon alpha-2a. Review of the literature identified 35 patients with PCH and pulmonary hypertension. The prognosis is poor and median survival was 3 years from the first clinical manifestation. Dyspnea and right heart failure are the most common findings of the disease. Hemoptysis, pleural effusion, acropachy, and signs of pulmonary capillary hypertension are less common. Chest X-ray or computed tomography scan usually shows evidence of interstitial infiltrates, pulmonary nodules, or pleural effusion. Hemodynamic features include normal wedge pressures. Radiologic and hemodynamic findings are undifferentiated from those of pulmonary veno-occlusive disease but differ from other causes of primary pulmonary hypertension. Epoprostenol therapy, considered the treatment of choice in patients with primary pulmonary hypertension, may produce pulmonary edema and is contraindicated in patients with PCH. Regression of lesions was reported in 1 patient treated with interferon therapy and 2 other patients stabilized, including our second patient. PCH was treated successfully by lung transplantation in 5 cases. Early recognition of PCH in patients with suspected primary pulmonary hypertension is possible based on clinical and radiologic characteristics. Diagnosis by pulmonary biopsy is essential for allowing appropriate treatment.