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Abstract Background Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. Methods We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. Results Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. Conclusions Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.

Background: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed., Material and Methods: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings., Results: The medians of TFRC in all individual participating centers were &gt; 12 weeks (range 14.0-36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks)., Conclusion: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

Background: Miniinvasive approaches are a long-term trend in surgery. Maximum possible quality of life after treatment of rectal cancer is a long-term goal. Adequate radicality of surgery is a long-term necessity. It is sometimes very difficult to fulfill all the above-mentioned requirements in low-level rectal cancer. By applying a multidisciplinary approach in the treatment of mildly advanced stages of low-seated malignant rectal tumor, a treatment procedure resulting in continence preserving can be offered to a selected group of patients meeting the strict indication criteria. We document our results with respect to a small number of patients in several interesting case reports., Cases: We are following up one patient after ideal treatment course achieving downstaging after neoadjuvant treatment, with uncomplicated operation and after operation period and with a long-term complete remission. One patient achieved dehiscence of the rectum suture. After secondary healing we observed a long-term remission. In one patient a rectovaginal fits developed outside the operation site. We were forced to abdominoperineal amputation. The pathological investigation of the specimen proved radically of the local excision and lack of lymphangioinvasion; nevertheless, a positive perirectal lymph node was found. The last case report shows the limits of imaging dia-gnostics. The liver lesions described as benign were in fact liver metastases of the early rectal cancer., Conclusion: According to the worldwide data available, the combination of neoadjuvant chemoradiotherapy and local excision by means of an operative rectoscope is a safe alternative to a resection surgery with total mesorectal excision in T2N0 rectal cancer. However, there is a need of other studies with more patients included, optimally randomized and prospective ones, which will support these claims. Supported by MH CR - DRO (MOÚ, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Carney triad is a synchronous or metachronous association of gastric gastrointestinal stromal tumors (GIST), pulmonary chondroma and extra-adrenal paraganglioma. The majority of patients have only one or two components of the triad, all three tumors being found in only about 2% of the patients at the time of the first diagnosis. The most common combination is gastric and pulmonary tumors. We report a case of Carney triad which was diagnosed at Masaryk Memorial Cancer Institute. A 57-year-old female patient with a history of gastric resection for leiomyosarcoma at the age of 14 and with an unclear pulmonary lesion evident on chest X-ray since as early as 2003. She was referred to our Clinic of Comprehensive Cancer Care after being diagnosed with unspecified tumors of the stomach, the left retroperitoneum and two liver metastases. Biopsy of the retroperitoneal mass was performed and histological examination showed pheochromocytoma. The patient underwent resection of the retroperitoneal tumor and wedge resection of the gastric tumor, left hemihepatectomy and left adrenalectomy (in two separate operations). The excised gastric tumor was a gastrointestinal stromal tumor (GIST) with a low risk of malignancy. Analysis of a liver specimen, however, showed two GIST metastases. No pathology was found in the left adrenal gland and the retroperitoneal tumor was positive for chromogranin A. Paraganglioma was thus diagnosed. Subsequently, mutational analysis of genes coding for succinate dehydrogenase subunits B, C and D (SDHB, SDHC, SDHD) and analysis of DNA methylation at the gene locus of SDHC was made. Carney triad was thus confirmed and the unclear pulmonary lesion could be described as benign chondroma. This report demonstrates the difficulty in distinguishing between Carney triad and Carney-Stratakis syndrome. Molecular information should improve the diagnosis of Carney triad.Key words: Carney triad - GIST pulmonary chondroma extraadrenal paragangliomaCarney-Stratakis syndrome.

Introduction: Gastrointestinal stromal tumors (GIST) are specific mesenchymal tumors of the gastrointestinal tract. Most of GISTs (95%) result from activating mutations in one of the receptor tyrosine kinase proteins (KIT). Tumor cells express this protein. GIST is most common in the stomach and small intestine, but may occur anywhere in the gastrointestinal tract and intra-abdominal soft tissues. The variety of its clinical presentations is related to localization of the tumor, its size and relationship to surrounding organs. Surgery is the first choice of treatment for patients with localized or potentially resectable tumors with the intention of R0 resection. Targeted therapy with imatinib (a selective inhibitor of the KIT protein) is the primary option for patients with metastatic GIST, as adjuvant treatment after surgery or neo-adjuvant therapy prior to surgery in indicated cases. This paper describes comprehensive therapy of GIST with an emphasis laid on the status of surgical treatment, and it highlights some controversial topics, e.g. the role of surgery for metastatic disease or neo-adjuvant targeted therapy., Conclusion: GIST is a relatively rare tumor most commonly affecting the stomach and small intestine. Surgical treatment is not replaceable in the treatment strategy of this disease. The diagnostic-therapeutic approach to patients with GIST must be comprehensive. Due to prescribing restrictions of biological therapies, these patients are inevitably directed to specialized centers where surgical treatment should also be preferably provided.

Inoperable c- kit negative gastrointestinal stromal tumor (GIST) is commonly considered to be highly resistant to systemic therapy. We present a case of a woman with an abdominal sarcomalike tumor diagnosed at the age of 26. The patient underwent several surgical procedures and courses of cytostatic therapy without any substantial effect. Later, the tumor was reclassified as c- kit negative GIST harbouring the mutation in exon 12 of PDGFRA gene. Hence, the therapy with imatinib mesylate was initiated, resulting in partial remission of metastatic lesions and further stabilization of the disease for five years to date. We therefore consider imatinib mesylate an appropriate therapy for c- kit negative GIST bearing PDGFRA mutations.

Background: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population., Patients and Methods: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated., Results: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies., Conclusion: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies.

In some patients, granulomatous reactions around foreign-bodies with FDG-PET positivity may be misinterpreted as malignancy. We report a case of a 31-year-old man diagnosed with testicular germinal tumor with retroperitoneal and left supraclavicular metastases. The diagnosis was based on left supraclavicular lymph node biopsy. Restaging examinations after orchiectomy and chemotherapy showed normalization of tumor markers and significant regression of the retroperitoneal infiltrate, however, with a residual FDG-PET positive lesion in the left supraclavicular fossa. The etiology behind this infiltration was revealed by a repeated histological examination, which surprisingly showed a foreign-body granuloma formation around a cotton pad left after the first surgery.

Objective: Surgically solved lung involvement in patients after surgery of colorectal cancer., Materials and Methods: Altogether 15 patients, 9 men (median age in the time of lung diagnosis 67 years) and 6 women (median age 59 years) underwent classical open pulmonary surgery during 2003-2008 years from the follow-up cohort of 836 persons after operation due to colorectal cancer in the time period of 1996-2008 years. The indication for lung surgery: solitary pulmonary lesion. Procedures distribution: pulmonary lobectomy 7, bilobectomy 2, segmentectomy 4, wedge resection 2. The requirement of the European Society of Thoracic Surgeons (ESTS) guidelines of complete pulmonary resection has been met by 10 operations (66.7%) with lobe specific lymphadenectomy. Histopathology investigation: Formalin fixed, paraffin embedded samples were investigated after hematoxylin-and-eosin staining, supplemented in case of need by immunohistochemistry of CK7, CK20 and TTF1., Results: Eleven pulmonary metastases were found, in two cases with interlobar lymfatics involvement. Two metachronous primary adenocarcinomas of the lung (ADL) were diagnosed, one of them with metastases into hilar lymphatics. In remaining two patients pulmonary chondrohamartoma was discovered., Conclusion: Solitary pulmonary opacity in patient after colorectal surgery might not represent simple metastasis explicitly. Complete resection is needed.

Background: An analysis of outcome data of pulmonary segmentectomy focused on local efficacy in primary non small cell lung cancer and true or seeming lung metastasis., Patients and Methods: Miscellaneous series of twenty patients treated with classical open procedure involving individuals with primary or metachronous non small cell lung cancer, solitary pulmonary metastasis of extrapulmonary cancer and/or benign pulmonary lesions, lung metastasis mimicing. Thirteen patients after segmentectomy because of malignancy are separated into a group of 7 cases with NSCLC up to 20 mm in diameter, and a group of 6 persons with solitary pulmonary opacity up to 38 mm treated previously surgically for extrapulmonary cancer. Both without enlargement of hilar and/or mediastinal lymphatics proven on preoperative CT imaging. Third part of the group collects benign pulmonary lesions: chondrohamartoma, pneumonitis and pulmonary infarct. Persons involved through a ten years period are followed up at 3 (4)-months intervals., Results: No perioperative and thirty day mortality was registered. Six cases of distant recurrence were recorded, three in NSCLC and three in extrapulmonary cancer patients. Five patients died within the follow-up period, three of them through the general progression of the oncological disease. Two deaths were non-cancer related. One R1 disease was discovered in a patient with primary lung adenocarcinoma. No local recurrence was recorded in both cancer series with median age of 63 yrs (range 45-79 yrs) and median duration of follow up 35 months., Conclusion: Lung segmentectomy seems to accomplish local control of early stage non small cell lung cancer and pulmonary metastasis of extrapulmonary cancer in selected patients.

Background: Testicular germ cell tumors (TGCT) are the most frequent malignancy seen in young men. More than 95% of patients diagnosed with early stage TGCT are cured. In management of stage I seminoma there are several treatment options, including adjuvant radiotherapy, adjuvant chemotherapy with one cycle of carboplatin or surveillance. Patients with stage I nonseminoma are treated with adjuvant chemotherapy, with nerve sparing retroperitoneal lymph node dissection or surveillance being considered another treatment alternatives for stage I disease., Methods and Results: Fifty five patients with stage I TGCT were diagnosed and treated in Masaryk Memorial Cancer Institute between January 2000 to December 2004. In a retrospective analysis, we reviewed treatment outcome and treatment strategy used in these patients. Patients characteristics also included histological subtype, risk status, age at the time of diagnosis, relapse rate, delayed toxicity, etc. Despite the small number of patients included in the analysis (55), there was observed a clear preference toward adjuvant radiotherapy in seminoma patients (95%) and adjuvant chemotherapy in nonseminoma patients (97%). During median follow up (5,6 years in seminoma group, 5,7 years in nonseminoma group) only two patients experienced relapse of disease in the seminoma group and none in the nonseminoma group. One patient died of metastatic colorectal cancer. Acute toxicity was acceptable, with no treatment related death. The long- term side effects were not significant (no grade 3 or 4 toxicity)., Conclusion: The achieved cure rates were high, with acceptable toxicity. The role of adjuvant chemotherapy with carboplatin in stage I seminoma remains controversial. Further management of TGCT should be guided by complete and correct assessment of known risk factors to ensure the potential for cure.

Background: Combination of cetuximab and irinotecan is an efficacious second- (and further-)-line treatment-alternative in patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan. In this retrospective study we present treatment results of patients treated combination of cetuximab and irinotecan in Masaryk Memorial Cancer Institute., Patients and Methods: Results were collected on forty-seven patients who started the therapy from July 2005 to February 2008. Primary outcomes were: response rate, time to progression and overall survival. Secondary outcomes were: treatment-related toxicity and identification of any predictive and prognostic markers. P-value was based on Gehan-Wilcoxon test or chi-square test and P-values < or = 0.05 were considered significant. The Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS)., Results: Forty-two patients were valuable for the treatment response. Objective response rate (complete and partial remission) was 35.7% (15 patients) and disease control (response and disease stabilization) was achieved in 30 patients (71.4%). The median time to progression was 6, 4 months (range 1, 5-25 months). On the date of statistical processing (median follow-up: 9, 2 months, range 2, 5-27 months) there were 26 patients alive and the median overall survival was 17, 1 months. We have confirmed correlation between the grade of the skin rush and the treatment response (p = 0.05) and time to progression ( p = 0.01), on the other hand there was no association between EGFR expression and these parameters. The therapy was also effective in 8 of 14 patients (57%), who had documented resistance to irinotecan., Conclusions: We have confirmed the efficacy of cetuximab and irinotecan combination for the therapy of patients with pretreated metastatic colorectal cancer. Our results are optimistic, but have to be validated in the course of time. The existence of nonresponding patients and by reason of pharmacoeconomy, we should give attention to the new molecular predictive and prognostic markers such as: K-ras-mutation and EGFR gene copy number.

Background: Incidence and mortality rates of colorectal malignancies in the Czech Republic are one of the highest in the world since over 7,500 patients are diagnosed yearly. About 25% of patients are diagnosed in clinical stage IV and in average more than 50% of patients who are diagnosed initially with resectable disease will relapse sooner or later. Management of palliative treatment of colorectal cancer therefore is becoming of a great importance., Observation: We designed a study protocol in 2005 and 16 patients with metastatic colorectal cancer were treated accordingly in the first line setting with XELIRI regimen (capecitabin, irinotecan) + bevacizumab. The regimen has proven high antitumor effectiveness (78% responses to treatment, median TTP: 12 months, 1-year survival reached 100% of patients) and excellent tolerance. No serious grade G3 or G4 toxicity was observed. Increase of blood pressure was observed sporadically within the group. We present below the case of 55 year old patient who underwent treatment of 4 cycles of XELIRI + bevacizumab and reached complete remission of the disease which lasted over the next 9 months (TTP 13 months)., Conclusion: Successful choice of a regimen of the first line treatment determines the next course of a disease including duration of patient's overall survival. We have confirmed within our pivotal population that combination treatment XELIRI + bevacizumab is a very effective and well tolerated regimen moreover suitable for administration at outpatient setting.

Administration of cytotoxic drugs is accompanied by many serious side effects, with cardiac toxicity as one of the most dangerous. In clinical practice anthracyclines are the best known chemotherapeutic agents linked to cardiotoxicity, however there are a number of other anti-cancer drugs (cyclophosphamide, taxans, trastuzumab, 5-fluorouracil, imunomodulators etc) that may cause cardiac toxicity as well. Basic mechanism through which anthracylines cause cardiac damage is recognized, though many pathogenetic ways of their toxicity still remain to be elucidated. Administration of trastuzumab is also clearly associated with cardiotoxicity, however, depression of left ventricular ejection fraction (LVEF) caused by this agent (unlike anthacyclines) seems to be fully reversible. For monitoring cardiotoxicity we use several methods--biochemical examination, use of X-ray, radionuclides or ultrasound. The most commonly used method to identify patients with heart damage is echocardiography with clinical examination. When a cardiac damage (mostly congestive heart failure with low LVEF) occures, following treatment depends on clinical symptoms and LVEF. These patients are then treated according to common internal medecine recommendations. Several cardioprotective agents have been tested, among these dexarazoxane seems do show significant cardioprotective activity. Also liposomal encapsulation of anthacyclines may reduce heart damage, especially early cardiotoxicity. Cardiotoxicity of cytostatic agents is a very serious side effect of anti-cancer therapy, which may affect survival more than the malignancy itself. Therefore a concentrated effort should be expended to prevent cardiac damage or at least to its early identification and prompt treatment.

Backgrounds: Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis., Design: The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined., Conclusions: No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer.

Chemoresistance assay results may play a role in cancer management decision process. Since August 2006 testing chemoresistance has been tested according to a protocol that was designed for this reason in our institute (Masaryk Memorial Cancer Institute). Five groups of different types of cancer in particular clinical stages were defined for chemosensitivity testing with: (1) metastatic malignant melanoma, (2) soft tissue sarcoma (STS), either primary or recurrent/metastic, (3) primary or metastatic renal cancer, (4) recurrent ovarian cancer and (5) other diagnosis "on clinician's request". In the period from September 2006 to November 2007, 25 samples of malignant melanoma (reproducible results in 9 cases), 29 samples of STS (relevant data in 11 cases), 36 samples of renal cancer (relevant results in 20 samples) and 16 samples of ovarian cancer (reproducible results in 11 cases) were acquired. Sensitivity to certain chemotherapy agent observed ex vivo does not necessarily mean that the cancer would also be sensitive to the same agent in vivo, however, ex vivo resistance with following in vivo sensitivity of the tumour has not been observed to date. The cultivation of malignant cells is very uncertain in solid tumours, which consist of several malignant cell multiclones (benign/stromal cells may outgrow malignant cells). This cultivation uncertainty as well as the unique complexity of human metabolism makes clinical application of chemoresistance testing at least very questionable. The small number of successfully evaluated samples has not yet provided us to carry out proper statistical evaluation and clinical application.

The primary endpoint of this study was to evaluate the efficacy (objective response rate; ORR) of combined chemotherapy with raltitrexed plus oxaliplatin as second-line treatment in patients with metastatic colorectal cancer (CRC). Secondary endpoints were overall survival (OS), time to progression (TTP) and toxicity (NCI-CTC criteria). The target population were patients with metastatic colorectal adenocarcinoma who progressed after first-line chemotherapy. Treatment consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion followed 45 minutes later by oxaliplatin 130 mg/m(2) IV as a 2-h infusion on Day 1, repeated every 3 weeks until further disease progression (PD), unacceptable toxicity or the decision of the patient. A total of 51 patients, all with WHO performance status 0-2 received a median of 6 treatment cycles (range 1-11). After 3 cycles, 8 of the 47 evaluable patients (17%) had experienced an ORR, 28 patients (59.6%) had experienced stable disease (SD) and 11 patients (23.4%) had PD. After 6 cycles, 1 of the 29 evaluable patients (3.5%) had an ORR, 13 patients (44.8%) had SD and 15 patients (51.7%) had PD. After a median follow-up of 48.9 weeks, median TTP was 18 weeks and median overall survival was 54.4 weeks. Treatment was well tolerated; grade 3 toxicities occurred in only 5/51 patients (9.8%). The most common toxicities were paraesthesia (62.7%), diarrhoea (23.5%), nausea (41.2%), vomiting (33.3%), hepatotoxicity (25.5%), and hematological toxicity (41.2%). In conclusion, the combination of oxaliplatin plus raltitrexed appears to be effective and well tolerated as second-line therapy in patients with disseminated CRC.

Purpose: Concomitant chemoradiotherapy prior to surgery of locally advanced rectal carcinoma (clinical T3- 4, and/or N+) might improve the therapeutic results. We report on our clinical experience with 34 patients receiving concurrent preoperative radiotherapy and capecitabine., Patients and Methods: Between September 2001 and March 2003, 34 patients with a median age of 62 years (range 18-75 years) were treated for adenocarcinoma of the rectum. Capecitabine was administered orally at a dose of 825 mg/m(2) twice-daily concomitantly every day during pelvic irradiation. The planned total dose of radiotherapy was 50.4 Gy, given with daily fractions of 1.8Gy, 5 days a week, over a period of about 5.5 weeks. Large pelvic dose (PTV-1) was 45.0 Gy/25 fractions in 5 weeks. Higher dose up to 50.4 Gy in further 3 fractions was given using boost fields (PTV-2). Radiotherapy was performed with high-energy photon beam (18 MV) linear accelerator using 3-dimensional (3D) treatment planning for 3 or 4 fields technique., Results: Toxicity was low: grade (G) 3 local dermatitis in 2 (6%), G3 diarrhea in 3 (9%) and G3 leucopenia in 1 (3%) patients. However, 2(6%) patients required drug dose reduction by 80%. Sphincter-sparing surgery was possible in 25 (76.5%) patients while 9 (26%) patients had radical surgery with removal of all macroscopic disease. Tumor mass downstaging by TNM criteria has been achieved in all of the treated patients. Pathological (p) complete response (CR) was verified in 7 (21%) patients and minimal microscopic residual cancer was found in 6 (17%) patients, for a total of 13 (38%) patients with substantial disease remission., Conclusion: Preoperative concomitant radiotherapy and oral capecitabine chemotherapy for locally advanced rectal adenocarcinoma appears to be an effective and safe therapeutic choice, improving the chance for rectal-sparing surgery. The follow-up time is rather short to evaluate time to progression and survival.

At diagnosis, nearly 50% of patients with carcinoma of the esophagus have a metastatic disease. Less than 60% of patients with locoregional disease can undergo a curative resection. Surgical principles include a wide resection of the primary tumor, including resection margins of 5 cm or more, plus regional lymphadenectomy. Radiotherapy alone can be considered for palliation in patients with locoregional disease who are medically unsuitable for surgery and in patients with contraindication for chemotherapy. The median length of survival is approximately 12 months. Effectiveness of chemoradiotherapy has been studied in randomized trials in patients with locoregional carcinoma (stage I-III). Chemoradiotherapy should include 50 to 60 Gy of radiotherapy plus concurrent chemotherapy with 5-fluorouracil (5-FU) plus cisplatin. Chemoradiotherapy is now an established alternative to surgical therapy (predominantly in patients with squamous cell carcinoma). In patients treated with chemoradiotherapy, a follow up endoscopy of the upper gastrointestinal tract 4 to 6 weeks after its completion is recommended. If a complete remission can be confirmed, patients are observed or offered esophagectomy. Patients with unresectable (T4) carcinoma can be treated with radiotherapy plus concurrent chemotherapy and those with adenocarcinoma of the distal esophagus with positive nodes should receive adjuvant postoperative radiotherapy and chemotherapy with 5-FU plus cisplatin.

Carcinoma of the anal canal represents about 1-2% of digestive system cancers. Its prognosis depends directly upon the size of the primary tumor and on the probability of lymphatic spread of the cancer. In the past, patients with invasive anal carcinoma were routinely treated with abdominal perineal resection. The NCCN institutions recommend that patients who have a carcinoma in situ can be cured with local excision with adequate margins. If margins are not sufficient, local radiotherapy is desirable. Patients who have a T1 lesion receive external beam radiotherapy (50-59 Gy) plus or minus mitomycin/5-fluorouracil. Patients with T2-T4 lesion, especially if inguinal nodes are positive, should receive the combination of mitomycin/5-fluorouracil plus radiotherapy (50-59 Gy) to include the inguinal and pelvic lymph node regions. Patients receiving the combination therapy (chemotherapy with radiation therapy) when compared with those with radiation therapy alone have a significantly better local control (60% versus 39%). Patients whose tumor was not eradicated are candidates for additional chemotherapy with 5-fluorouracil/cisplatin. If the local disease is persistent or progressive or if it has the local recurrence, patient becomes a candidate for an abdominoperineal resection.

The article summarizes practical guidelines for the management of rectal cancer. Colorectal cancer alone accounts for about 100,000 death in Europe and 75,000 in the US each year. The current cornerstones of treatment are surgery, radiotherapy (for rectal cancer only) and chemotherapy. At diagnosis the most important factor predicting treatment outcome is the stage of disease. Patients with rectal carcinoma should be classified according to the stage of the disease, including endorectal ultrasound and biopsy of the lesion. Five years after diagnosis, survival reaches about 50%. For early stage disease, surgery remains the standard treatment, but patients with lymph node-negative T3 or T4 lesions or with any lymph node-positive cancer should receive adjuvant radiotherapy and chemotherapy following the surgery. Pelvic radiation therapy decreases local recurrence; the addition of systemic chemotherapy further enhances local control and improves the survival. In patients with T3 or T4 rectal carcinoma the pre-operative therapy (radiation therapy combined with systemic chemotherapy) has potential advantages, including the decreased tumor, less acute toxicity compared with postoperative therapy, increased radio sensitivity due to more oxygenated cells, and enhanced sphincter preservation.

Gastric carcinoma is often diagnosed at the advanced stage. Approximately 50% of patients with locoregional disease cannot undergo any curative resection. 5-year survival rate in patients who undergo a curative resection (R0) ranges from 30-40%. In patients with curatively resected gastric carcinoma who are at high risk of relapse the adjuvant postoperative chemotherapy with 5-FU/leucovorin is recommended. It should be followed by radiotherapy with concomitant 5-FU/leucovorin, and then two more courses of 5-FU/leukovorin (INT-0116 trial) should be added. For the surgery alone group, the overall survival was 27 months; in the chemoradiotherapy group it was 36 months. The recommended therapy for inoperable or medically unsuitable patients with locoregional carcinoma is the combined radiation therapy (45 to 50.4 Gy) with concurrent 5-fluorouracil or cisplatin based chemotherapy.