Unresponsive or non-compliant steatorrhea in cystic fibrosis?

AbstractIn 105 pancreatic insufficient CF patients (steatorrhea and low fecal elastase-1 concentrations), the effectiveness of pancreatic enzyme therapy (PET) has been assessed (fecal fat losses and coefficient of fat reabsorption). Eight unresponsive subjects were checked for PET compliance with fecal chymotrypsin assay. Three patients were documented to be non-compliant. Unresponsive patients should undergo evaluation for PET compliance

A jejunal stromal tumour in a patient with metastatic neuroendocrine cancer of unknown origin; a rare coexistence, diagnostic and therapeutic challenge

Pacjentkę 59-letnią przyjęto do Kliniki Gastroenterologii z powodu postępującego spadku masy ciała, biegunki o niewyjaśnionej etiologii, oraz wykrytych w badaniu ultrasonograficznym licznych ognisk hyperechogenicznych w wątrobie. Wykonano celowaną biopsją cienkoigłową i rozpoznano zmiany przerzutowe o utkaniu neuroendokrynnym o wysokim stopniu zróżnicowania (cytologia + immunohistochemia). Badania biochemiczne wykazały podwyższone stężenie chromogranin A (CGA) w surowicy krwi i zwiększone wydalanie kwasu 5-hydroksyindolooctowego (5-HIAA) w dobowej zbiórce moczu. Scyntygrafia receptorowa ujawniła dodatnią ekspresję receptorów somatostatynowych w obrębie zmian w wątrobie, natomiast nie znaleziono żadnego pozawątrobowego patologicznego ogniska gromadzenia znacznika mogącego odpowiadać pierwotnemu guzowi neuroendokrynnemu. Rozpoczęto leczenie objawowe długodziałającym analogiem somatostatyny i równolegle do tego podjęto decyzję o zakwalifikowaniu pacjentki do celowanej peptydowej receptorowej terapii radioizotopowej. W tym celu wykonano kontrolne badanie tomografii komputerowej jamy brzusznej, które oprócz zmian w wątrobie, wykazało nieopisanego wcześniej dobrze unaczynionego guza w jelicie cienkim (pierwotny guz neuroendokrynny?). Pacjentkę skierowano do leczenia operacyjnego. Ku zaskoczeniu autorów pracy badanie histopatologiczne wykazało dodatnią ekspresję CD117 potwierdzającą rozpoznanie rzadkiego guza stromalnego jelita cienkiego. Dwa miesiące później rozpoczęto peptydową receptorową terapię radioizotopową z użyciem 90Y/77Lu-DOTA-TATE. Pacjentka otrzymała dwie dawki tego leku, obecnie jest stabilna, zaplanowano dalsze leczenie.A 59-year-old woman presented to the Department of Gastroenterology complaining of progressing weight loss, unexplained diarrhoea, and, as revealed by abdominal ultrasound, numerous hyperechogenic foci in the liver. The immunohistochemical evaluations of the specimens from biopsy revealed well-differentiated hepatic neuroendocrine metastases. The biochemical marker levels, including serum chromogranin A (CGA) and urine 5-hydroxyindolacetic acid (5-HIAA) 24-hour excretion, were significantly elevated. Whole body somatostatin receptor scintigraphy showed tracer accumulation in the liver lesions, with no extrahepatic tumour, possibly the primary origin. Long-term somatostatin analog therapy was initiated and a peptide-receptor targeted radionuclide therapy decision was made parallel to this treatment. Therefore, a followed-up CT scan of the abdomen showed, as well as the metastatic changes within the liver, a wellvascularised jejunal tumour suspected to be the primary focus of the disseminated neuroendocrine neoplasm. Unexpectedly, the pathological examination revealed a positive cell reaction for CD 117, confirming the diagnosis of a rare jejunal stromal tumour. Two months later peptide-receptor therapy with 90Y/77Lu-DOTA-TATE was commenced

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5%) in the comparison with the follicular areas (2 +/- 1%). The evaluation of the thyroid transcription factor 1 (TTF-1) expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer

Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5%) in the comparison with the follicular areas (2 +/- 1%). The evaluation of the thyroid transcription factor 1 (TTF-1) expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients

Abstract Background Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. Methods Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. Results Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance ( P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously ..