[Features of type 2 diabetes mellitus and its pharmacotherapy in outpatients].

BACKGROUND: Type 2 diabetes mellitus (DM) remains the most common type of DM and is associat-ed with disabling complications, reduced quality of life and reduced life expectancy. Satisfactory control of carbohydrate metabolism remains the key way to manage them. AIM: To perform a retrospective analysis of carbohydrate metabolism (in terms of glycated hemoglobin - HbA1c), the prevalence of complications, and features of hypoglycemic and concomitant therapy in patients with type 2 DM. MATERIALS AND METHODS: The analysis of sex and age characteristics, achieved level of HbA1c, diabetes complications, sugar-reducing and concomitant therapy according to the data of outpatient records of the patients who are on dispensary registration with an endocrinologist in the Endocrinology Department of the Consultative and Diagnostic Polyclinic of the Tomsk Regional Clinical Hospital in Tomsk was carried out. RESULTS: 546 outpatient medical records of patients with type 2 DM were analysed, among which there were 39.6% men (n=216) with a history of type 2 DM 8.0 years [3.0; 13.0] , median age 64.0 years [54.5; 71.0] and 60.4% women (n=330), history of type 2 DM 10.0 years [5.0; 15.0], median age 70.0 years [63.0; 75.0]. The achieved HbA1c level in men was 7.6% [6.3; 9.0] and in women 7.4% [6.4; 9.1]. 19.4% of men and 13.6% of women had an aggravated history of type 2 DM. According to the history, 6.5% of men (n=14) and 3% of women (n=10) with type 2 DM had a history of stroke, and myocardial infarction 12% (n=26) and 1.5% (n=5), respectively. Among the analysed outpatient records of type 2 DM patients, 18.5% of men (n=40) and 12.4% of women (n=41) were found to have diabetic nephropathy. Diabetic retinopathy was reported in 9.3% (n=20) of men and 4.2% (n=14) of women. Diabetic macroangiopathies were detected in 29.6% (n=64) of males and 9.7% (n=32) of females. Among other chronic complications of DM, diabetic neuroosteoarthropathy was recorded in 1% (n=2) of males and 3% (n=10) of females, diabetic polyneuropathy in 25% (n=54) and 21.5% (n=71), respectively. Diabetic foot was diagnosed in 1.9% (n=4) of men and 1.8% (n=6) of women. Among comorbid pathology, obesity was diagnosed in 45.4% (n=88) of men and 69.1% (n=228) of women, dyslipidaemia in 10.2% (n=22) and 10.6% (n=35) respectively, hypertension in 39.8% (n=86) and 32.6% (n=108) of cases. The diagnosis of non-alcoholic fatty liver disease was verified in 3.7% of men (n=7) and 1.8% of women (n=6), chronic heart failure in 7.4% of men (n=16) and 2.4% of women (n=8) registered for type 2 DM. According to the analysed outpatient records, 4.1% (n=23) of patients received diet therapy, 48.3% (n=263) received monotherapy and 47.6% (n=260) received combination therapy for type 2 DM. Metformin was the most commonly used monotherapy for type 2 DM 36.1% (n=197), followed by insulin 6.9% (n=38), sulfonylurea derivatives - 2.7% (n=15). Combination of metformin and dipeptidyl peptidase-4 inhibitors (13.9%) was the most commonly used combination therapy. CONCLUSION: Analysis of the current situation in the diabetology service will help to identify weaknesses and strengths, which is necessary to optimise existing therapeutic approaches in accordance with current clinical recommendations.

[THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

[LONG-TERM RESULTS OT SURGICAL ABLATION OF LEFT ATRIAL GANGLIONAR PLEXUS IN PATIENTS WITH CORONARY HEART DISEASE AND ATRIAL FIBRILLATION].

We evaluated long-term results of epicardial radio-frequency ablation of anatomical zones of left atrial ganglionar plexuses (GP) during aortocoronary bypass surgery in patients with coronary heart disease and atrial fibrillation (AF). In 2010-2012, radio-frequency ablation of GP was performed in 92 patients with AF. The patients were divided into 3 groups depending on the form of AF. Group 1 comprised patients with paroxysmal AF, group 2 with persistent AF, group 3 with long-standing persistent AF. Mean duration of observation was 14.4 ± 9.6 months. Radiofrequency ablation of GP anatomical zones combined with aortocoronary bypass surgery markedly improved the clinical and functional conditions of the patients and allowed to preserve the sinus rhythm for a long period in 78.6% and 39% of them presenting with paroxysmal and long-standing paroxysmal AF respectively.

[The use of implantable devices for long-term monitoring of cardiac rhythm after surgical treatment of atrial fibrillation in patients with ischemic heart disease].

We present in this paper experience of the use of implantable devices for long-term monitoring of cardiac rhythm after one stage operation of coronary artery bypass grafting (CABG) and radiofrequency ablation of atrial fibrillation (AF) source and results of a prospective randomized study, in which we included patients (n=95) with persistent AF and ischemic heart disease. These patients were randomized into 3 groups: with radiofrequency isolation of ostia of pulmonary veins (group 1, n=31), radiofrequency modified mini-maze procedure (group 2, n=30); CABG without AF elimination (control group 3, n=34). Implantable devices Reveal XT were used in 53 patients (21, 25, and 7 in groups 1, 2, and 3, respectively). According to data obtained with these devices AF was absent in 86.7, 95.6, 53%, and in 80, 86.2, 44.1% of patients in groups 1, 2, 3 after 1 and 2 years after operation, respectively). In 24% of patients Reveal devices also registered asymptomati-c arrhythmias. The use of implantable devices for monitoring of rhythm allowed to detect such arrhythmia and to provide timely correction of therapy.

[The role of autonomous nervous system in the development of atrial fibrillation].

Atrial fibrillation (AF) is a challenging medical problem accounting for the development of stroke, thromboembolism, and cardiac failure. Disbalance in the autonomous nervous system (ANS) is a leading cause of AF. There is definitive evidence of the relationship between vegetative innervations, initiation and maintenance of AF, the main contributors being hyperactivity of ANS and uncontrolled release of neurotransmitters that shorten atrial refractoriness. The neurotransmitters make up the triggering mechanism of AF. The present review focuses on the role and mechanism of AF in ANS disbalance.

Cytogenetic biomarkers for the assessment of the influence of pollution on natural fish populations.

Cytogenetic analysis methods were used to study the developing embryos of the following four Coregonidae species: Coregonus peled (Gmelin), Coregonus lavaretus (Gmelin), Coregonus nasus (Pallas) and Coregonus muksun (Pallas). Spawners of these species were selected from rivers and lakes of the Tyumen region (Russia) with different levels of pollution. The variability of the chromosomal aberration rate was analyzed during a monitoring period of more than 20 years. The level of chromosomal mutability in the embryonic cells of these fishes was found to have steadily increased during the observation period (1989-2011). The higher frequency of chromosomal mutations at different stages of embryogenesis in broad whitefish, C. nasus (Pallas), was noted in comparison with other species. The possible use of chromosomal mutation frequency as an indicator (biomarker) to characterize the state of a population is discussed.

Metaplastic carcinoma of the breast: clinicopathological features and immunohistochemical analysis.

PURPOSE: Metaplastic breast carcinoma (MBC) is a rare and heterogeneous group of neoplasms characterized by a mixture of spindle, squamous and/or mesenchymal cells. The purpose of this study was to assess the immunohistochemical features, biological characteristics and myoepithelial differentiation of a series of MBC patients. METHODS: The archival pathological material from 33 MBC patients was evaluated. Analysed were patient characteristics, pathological and immunohistochemical features and their relevance as prognostic factors of patient survival. RESULTS: The median patient age was 44 years (range 17-82), and the median tumor size 5 cm (range 0.5-17.0). The majority of patients (n=29; 87.8%) were treated by modified radical mastectomy, 1 (3%) patient had breast-conserving surgery and another 1 (3%) had latissimus dorsi flap reconstruction. Metastasis to axillary lymph nodes was found in 14 (42.4%) patients, 18 (54.5%) patients were triple negative, and 22 (66.7%) were epidermal growth factor receptor (EGFR) positive. The 5-year event-free survival was 25.9%, whereas the 5-year overall survival was 27.5%. Immunohistochemical analysis showed the following: vimentin positivity in 31 (93.9%) patients, high molecular weight cytokeratin (HMWCK) positivity in 31 (93.9%), CK 5/6 positivity in 28 (84.8%), P 63 positivity in 19 (57.6%) and calponin positivity in 18 (54.5%) patients. Two particularly interesting findings were noted, namely, myoepithelial differentiation in the carcinomatous and sarcomatous elements of MBC, and EGFR immunopositivity. CONCLUSION: Immunohistochemistry has an important role to play in the diagnosis and treatment decision of MBC. This report presents findings related to a broad panel of immunohistochemical markers for a large series of metaplastic cases, which indicate poor prognosis for this tumor.

Staining characterization by immunohistochemistry of tumor cancer antigen in patients with endometrial cancer.

OBJECTIVE: The aim of the present study was to evaluate the correlation between the pattern of cancer antigen (CA-125) expression by immunohistochemistry and pathologic parameters in endometrial carcinoma. METHODS: Seventy-two cases of primary uterine carcinomas, 66 endometrioid carcinoma and six non-endometrioid, were analyzed by immunohistochemistry for CA-125 expression. Myometrial invasion was evaluated by assessing the percentage of myometrial thickness involved at the site of deepest tumor extension. Presence or absence of vascular invasion, cervical stromal invasion, lymph node metastasis, and ovarian metastasis from endometrial cancer was assessed. Tumor size was measured by the maximum diameter. Peritoneal washings were examined for the presence or absence of cancer cells. The extent and location of immunohistochemical staining for CA-125 was assessed according to the immunoreactive score (IRS) that evaluated the proportion of cells expressing CA-125 and the intensity of staining. Percentage of the cancer area stained in high-power fields was examined. Staining intensity was graded as 0 (negative), 1 (weak), 2 (modarate), and 3 (strong); percentage of positive cells examined was scored as 0 (negative), 1 (< 10%), 2 (11-50%), 3 (51-80%), and 4 (> 80%). The two scores were multiplied and the IRS (values from 0-12) was determined: 0 as negative, values 1-3 as weak, values 4, 6 as positive, and multiplication values 8, 9, 12 as strongly positive. RESULTS: Of the 72 patients, 66 (91.7%) had endometrioid carcinoma and six (8.3%) had non-endometrioid carcinoma. Of the seventy-two patients, 38 (52.7%) had surgical Stage I disease, 12 (16.7%) had Stage II, 16 (22.2%) had Stage III disease, and six (8.4%) had Stage IV disease. Ten (14.7%) of the 68 patients who underwent lymphadenectomy had positive nodes. Nine (12.5%) of 72 patients had positive peritoneal cytologic findings. Forty-eight (66.7%) patients had deep myometrial invasion, 29 (40.3%) had lymphovascular invasion, 25 (34.7%) had cervical stromal involvement, and 12 (16.7%) had ovarian metastasis. Twenty-eight (38.9%) patients had grade 1, 25 (34.7%) had grade 2, and 19 (26.4%) had grade 3 disease. Fifty-nine (81.9%) patients had a tumor size greater than 2 cm. Negative staining was noted in ten (13.9%) tumors, weakly positive in 23 (31.9%), positive in 16 (22.3%) and strongly positive in 23 (31.9%). Grade 0 intensity was found in nine (12.5%) tumors, grade 1 in 16 (22.3%), grade 2 in 21 (29.16), and grade 3 in 26 (36.11). Negative percentage of positive cells examined was found in nine (12.5%) tumors, < 10% in 19 (26.38%), 11-50% in 18 (25%), 51-80% in 13 (18.05%), > 80 in 13 (18.05%). We found that intensity, percentage of positive stained cells, and IRS correlated with deep myometrial invasion (p < 0.05). CONCLUSIONS: Intensity, percentage of positive stained cells for CA-125, and IRS can be used to determine the need for abdominal hysterectomy and lymphadenectomy for staging in endometrial cancer.

The potential energy surface of the Ar-CO complex obtained using high-resolution data.

A potential energy surface is retrieved for the Ar-CO complex by carrying out a global analysis of its high-resolution spectroscopic data. The data set consists of already published microwave and infrared data and of new microwave transitions which are presented in the paper. The theoretical approach used to reproduce the spectrum is based on a model Hamiltonian which accounts simultaneously for the two large amplitude van der Waals modes and for the overall rotation of the complex. Only the vCO = 0 state is considered. The root-mean-square deviation of the analysis is 18 MHz for the microwave data and 1.4 x 10(-3) cm(-1) for the infrared energy difference data. Fifteen parameters corresponding to the potential energy function are determined in addition to two kinetic energy parameters and two distortion-type parameters. The potential energy surface derived is in good agreement with the one obtained by Shin, Shin, and Tao [J. Chem. Phys. 104, 183 (1996)].

[Cytogenetic approach to estimation of developmental stability of the natural population of coregonid fishes]. / Tsitogeneticheskii podkhod otsenki stabil'nosti razvitiia prirodnykh populiatsii sigovykh ryb.

A comparative cytogenetic analysis of coregonid fish was carried out in the river and lake ecosystems of the northern Tyumen' District. The occurrence of chromosomal aberrations in embryonic cells of fish steadily increased during the period from 1989 until 2001. Possible causes of this dynamic are discussed.

Gastroduodenal metastases in a clear cell sarcoma patient.

Clear cell sarcoma is a rare tumor with an unpredictable clinical course and usually poor prognosis. Almost all of the patients will have pulmonary metastases during the clinical course. Other more common metastatic sites are bones, lymph nodes, liver and spleen. Treatment of clear cell sarcoma is primarily surgical aiming to achieve uninvolved margins. Role of chemotherapy, radiotherapy and immunotherapy is controversial and remission of metastases has been reported rarely. In this study we report a case of clear cell sarcoma, with gastroduodenal and pulmonary metastases and remission of these metastases in response to chemotherapy.

Primary gastrointestinal tract lymphomas.

AIM: To evaluate the prognostic factors and treatment modalities affecting survival in patients with primary gastrointestinal tract lymphoma. MATERIAL AND METHODS: Gastrointestinal tract lymphoma patients were retrospectively studied. Age and sex of patients, location and histopathological grade of tumour, stage of disease, extent of surgical resection and chemotherapy were evaluated as prognostic factors. Effects of clinicopathological and treatment associated factors on disease-free and overall survival were calculated in univariate and multivariate analyses. RESULTS: On univariate analysis, disease stage (p = 0.002), extent of surgical resection (p = 0.003) and chemotherapy (p = 0.001) were found to be significantly affecting overall survival and none of the studied factors were found to be related with disease-free survival. Multivariate analysis revealed that grade of the tumour (p = 0.042) and chemotherapy (p = 0.028) significantly affected disease-free survival and disease stage (p = 0.013) and chemotherapy (p = 0.0003) were independent prognostic factors for overall survival. In addition, surgery and chemotherapy in combination, significantly increased overall survival compared to surgery or chemotherapy only. CONCLUSION: Early stage patients have a better survival and it could be prolonged if surgery with no residual disease is performed; adjuvant chemotherapy provides an additional benefit.

High resolution TDL spectroscopy of the Ar-CH4 complex.

The spectrum of the weakly bound complex Ar-CH4 in the 7 microm region was discovered, analysed, and compared with a spectrum, predicted from ab initio calculations. The measurements were made by probing a supersonic gas expansion with a tunable diode laser (TDL). Several bands of Ar-CH4 associated with different ro-vibrational transitions of the v4 vibration of CH4 were recorded and analysed in a spectral region from 1295 to 1330 cm(-1). In particular the following transitions were studied: j = 1 <-- 0 (at 1311 cm(-1)) reported in Pak et al. [Z. Naturforsch. 53 (1998) 725], j = 0 <-- 1 (at 1301 cm(-1)), j = 2 <-- 1 (at 1316 cm(-1)), and j = 3 <-- 2 transitions (at 1322 cm(-1)). Here, j denotes the angular momentum of the methane unit inside the complex. Analysis of the recently recorded j = 1 <-- 1 transitions at about 1306 cm(-1) in the region of methane Q(1) is in progress. The experimental results are compared with ab initio calculations. The close agreement between observed and ab initio spectra is convincingly demonstrated with respect to the gross spectral features, including many details of the spectra.

Doppler-free two-photon millimeter wave transitions in OCS and CHF3.

Doppler-free two-photon rotational transitions J = 13<--<--11 and J = 12<--<--10 of OCS and J = 8<--<--6 and J = 7<--<--5 of CHF (3) were detected in the frequency range 134-156 GHz, using a novel, highly sensitive intracavity-jet technique. The sub-Doppler narrowing of the observed peaks (down to 40 kHz full width at half maximum as compared to 300 kHz of the Doppler width) demonstrates the potential of this new technique for high precision millimeter wave spectroscopy. The possibilities of the further reduction of the two-photon absorption line widths are considered.

Lymphatic mapping and sentinel lymphadenectomy in early stage breast carcinoma.

The rate of axillary lymph node metastases is low in early stage breast carcinoma and axillary lymph node dissection is controversial in the treatment of these patients. Intraoperative lymphatic mapping technique is suggested for the identification of metastatic lymph nodes. Intraoperative lymphatic mapping was performed on 60 clinical stage I and II patients who were treated at Ankara Oncology Hospital between 1996-1998. Patent blue dye was injected in all cases, as the tumor was totally excised before mastectomy, into the surrounding breast tissue at four different quadrants. Presence of metastases were examined on stained lymph nodes (sentinel lymph node: SLN) by frozen-section. Modified radical mastectomy was performed including level I, II, III lymph node dissection. Metastases were evaluated on the remnants of frozen-section tissues and unstained lymph nodes (nonsentinel lymph node: nSLN) in axilla on hematoxyline-eosin stained slides and by immunohistochemistry. Forty-nine (81.6%) SLNs were identified among 60 cases. In 18 (36.7%) of these 49 patients, metastases were detected in SLNs by frozen section. In one case micrometastasis was detected in the remnants of frozen-section by immunohistochemistry though it was negative with hematoxyline-eosin. There were no metastases in nSLNs of 27 cases whose SLNs's frozen-sections were tumor free. In 3 cases SLNs were negative but metastases were detected in nSLNs (false negative: 6.1%). There were no local or systemic complications due to injections of dye. Selective lymph node dissections can be performed on early stage breast cancer patients by means of lymphatic mapping. This minimally invasive technique identifies metastatic axillary lymph nodes with a high degree of accuracy, so we can suggest that, non-metastatic patients can be treated without axillary dissection.

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy.

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent 99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with 99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of 99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.

Submillimeter Detection of the van der Waals Stretching Vibration of the Ar-CO Complex.

With the Cologne submillimeter-wave supersonic jet spectrometer, we extended molecular jet spectroscopy with backward wave oscillators up to frequencies of about 600 GHz. For the first time, the van der Waals stretching vibration of the Ar-CO molecular complex was detected in direct absorption. We measured 13 ro-vibrational transitions (Kvstretch = 1 <-- 0, Ka = 0 <-- 0) in the frequency range from 528 to 600 GHz and additionally the two R(3) K doublet (Ka = 4 <-- 3) pure rotational transitions at 447 GHz with an accuracy of about 200 kHz. The ro-vibrational transitions were assigned and fitted within experimental accuracy to a simple Hamiltonian taking into account the Coriolis interaction between the stretching and bending states, i.e., between vstretch = 1, Ka = 0, and vbend = 1, Ka = 1. The intensity of the transitions in the van der Waals stretching mode was estimated to be a factor of 5-10 less than that in the bending mode of Ar-CO. Copyright 1999 Academic Press.

Secretory breast carcinoma in a boy.

Secretory breast carcinoma is a very rare condition in boys. An 11-year-old boy with secretory breast carcinoma is presented here. Modified radical mastectomy was performed by irradiation and chemotherapy because of axillary metastasis. There was no local recurrence or distant metastases in the follow-up period of 14 months.

Cumulation of TP53 mutations and p16INK4A/p15INK4B homozygous deletions in human papilloma virus type 16 positive scrotal cancer.

Scrotal cancer is the first described occupational cancer. The frequency of occupation-related scrotal cancer is very rare because of better hygiene and protective clothing. Human papilloma viruses (oncogenic types 16 and 18) were reported as the causative agents in the pathogenesis of scrotal cancers. E5, E6, and E7 proteins, expressed by human papilloma virus type 16, affect the cell cycle at the G1 checkpoint. TP53, p16INK4A, and p15INK4B were reported as the transcription factors that regulate the cell cycle on the same pathway. Here, the mutation pattern of TP53, p16INK4A, and p15INK4B genes and the homo/hemizygous deletion patterns of p16INK4A/p15INK4B genes are presented in four scrotal carcinoma cases. The results were correlated with the findings of oncogenic human papilloma viruses (types 16 and 18) in this panel. In two of four case, human papilloma virus type 16 was observed. Homozygous deletion in p16INK4A/p15INK4B genes and a codon 259 missense point mutation (GAC-->TAC; Asp-->Tyr) in the TP53 gene were observed in one human papilloma positive scrotal carcinoma case. The homozygous deletion in p16INK4A/p15INK4B genes was observed in another human papilloma positive scrotal carcinoma case. The cumulation of TP53 mutations and p16INK4A/p15INK4B homozygous deletions in human papilloma virus type 16 positive scrotal carcinoma cases indicate that the alterations of TP53, p16INK4A, and p15INK4B genes have an important role in the progression of scrotal cancers, as well as other factors. The survival rate for the two human papilloma virus type 16 positive patients who had a TP53 mutation or p16INK4A/p15INK4B homozygous deletion or both was lower than that for the human papilloma virus type 16 negative cases who had no TP53, p16INK4A, and p15INK4B mutation. The molecular alteration of TP53, p16INK4A, and p15INK4B genes may be useful as a prognostic marker in scrotal cancer.