Aim: To study the relationship between the genotype and the phenotype in the patients with Hermansky — Pudlak syndrome (HPS) associated with granulomatous colitis; to monitor clinical course of the disease for adequate treatment, cancer surveillance and genetic counseling. Materials and Methods: The diagnosis of HPS is established by physical examination, chest X-ray, computed tomography, endoscopic examination with biopsy, and laboratory tests, including histology, baseline laboratory blood, urine and feces tests, determination of ASCA-C and ANCA antibodies using an ELISA. Molecular genetic testing for HPS gene mutations, R702W, G908R, L1007fs and P268S mutations in NOD2 gene, and TaqI variant of the VDR gene were carried out. Results: We report 2 cases of HPS from unrelated families. Both were complicated by inflammatory bowel disease with pathologic features of Crohn’s disease refractory to antibiotics and corticosteroids. One patient (family 1) with Ashkenazi Jewish ancestry had pathogenic variant of the HPS-4 gene in exon 8, mutation P268S of NOD2 genes and “Tt” genotype of TaqI variant of the VDR gene. Another patient (family 2) carried two mutations P268S and G908R of NOD2 gene, and had a large paraovarian cyst diagnosed. No consistent success with the standard medical therapy, used for treating granulomatous colitis, associated with HPS, in presented cases was achieved. Patients needed surgical interventions at a young age and a long-term surveillance of the probable development of tumors and other complications. Azathioprine at 2 mg/kg/day and mesalazine 3 g/day were used with some positive effect for prevention of Crohn’s disease postoperative recurrence. Conclusion: The occurrence of perianal lesions, the histopathological findings and the results of the molecular genetic analysis confirmed the mutations P268S and G908R of NOD2 gene in these cases suggest that HPS was truly associated with Crohn’s disease variant with early onset and severe course. The search for the molecular causes of the disease in some individuals may help in the development of new therapeutic and surgical approaches, as well in the improvement of understanding of premalignant inflammatory conditions in a large bowel.

АSSOCIATION OF COLOPROCTOLOGISTS OF UKRAINE. NATIONAL RECOMMENDATIONS OF ASSOCIATION OF COLOPROCTOLOGISTS OF UKRAINE FOR MANAGEMENT OF PATIENTS WITH HEMORRHOIDS, аdаpted for Guidelines of European Society of Coloproctologists (ЕSСP)

Diagnosis and tactics of surgical treatment of colorectal cancer that developed during pregnancy

Мета. Порівняти клінічні характеристики пацієнтів при хворобі Крона (ХК) за віком, статтю, вираженістю загальних симптомів, тяжкістю перебігу та оперативними втручаннями, у яких виник / не виник колоректальний рак (КРР). Матеріали і методи. Порівнювали клінічні характеристики та результати хірургічного лікування 98 пацієнтів з ХК (1-ша група) та 16 пацієнтів (2-га група) у яких виник КРР. Результати. Оперативні втручання на тонкій і товстій кишці виконані у 62,3% пацієнтів при ХК, у тому числі правобічна геміколектомія (у 14,3%) і тотальна колектомія (в 11,2%). З хворих 1-ї групи, яким здійснено тотальну колектомію, більшість 63,6% належали до вікової групи А2, в усіх локалізація процесу L2, 90,9% з них жінки. У 2-й групі найчастішою операцією була лівобічна геміколектомія (у 50% хворих), переважали чоловіки вікової групи А3.

Aim: To determine the frequency of NOD2 gene c.3019-3020insC (rs5743293) and c.2104C>T (rs2066844) allelic variants in the patients with Crohn’s disease (CD), colorectal cancer (CRC) and in the control groups and to study the association of these mutations with the onset time of the diseases, gender and surgical interventions. Materials and Methods: The diagnoses of CD and CRC were established based on standard clinical examination and laboratory tests. Molecular genetic study of a frameshift 3020insC mutations of NOD2 gene were performed in 54 patients with CD; missense R702W mutations of the NOD2 gene — in 41 CD patients and 38 healthy controls. In CRC group, 3020insC mutation was tested in 48 patients, R702W mutation — in 40 patients and 40 healthy controls. PCR-RFLP technique was used to identify the mutations. Results: The frequency of the minor allele (M) of 3020insC mutation of NOD2 gene in the patients with CD was significantly higher than in the control group (р = 0.01). The age at CD onset in females carrying 3020insC mutation was significantly lower (22.5 ± 1.6 years) when compared with females without the mutation (32.7 ± 2.5 years) (p = 0.002). There was no significant difference in the allele frequencies and genotype distributions of R702W mutation in the patients with CD in comparison with the controls. The mean age at CD onset in the patients carrying R702W mutation was significantly lower (28.4 ± 1.4 years) compared with the patients without the mutation (39.4 ± 2.8 years) (p < 0.01). Surgical interventions for CD was required in 40.0% of 3020insC mutation carriers. Among patients with CRC, only 4.2% carried 3020insC mutation and 20.0% R702W mutation. Our study suggests that R702W and 3020insC mutations are not associated with the risk of CRC in Ukrainian patients. There was no statistically significant difference in mean age at CRC onset in patients with/without R702W mutation. Only one patient with CRC had two mutations. Conclusion: The earlier age at CD onset was associated with 3020insC mutation, but only in female patients. The association between R702W mutation and the earlier age of CD onset was found. Patients with 3020insC mutation showed a trend to a higher frequency of surgical interventions for CD.