Abdominal emergencies in surgical oncology.

INTRODUCTION: In general, abdominal emergencies are urgent situations that require a prompt and correct diagnosis and treatment. They involve a broad spectrum of diagnoses and can occur in all age groups. The situation is often modified in oncologic patients according to the extent and level of progression of the primary oncological disease. METHODS: A retrospective study was conducted to analyze the group of adult patients with abdominal emergencies treated in Masaryk Memorial Cancer Institute between 2011-2017. RESULTS: In total, 601 patients underwent emergency surgery during the 7-year period. The causes included gastrointestinal obstruction (43%), intra-abdominal inflammatory complications (33%) and bleeding (17%). Acute appendicitis or cholecystitis was the cause in only less than 4% of all patients. CONCLUSION: The problems of acute abdominal emergencies in oncologic patients are substantially different from those in the general population, particularly in terms of the causes where gastrointestinal obstruction is the leading cause.

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastases from colorectal cancer in the Czech Republic in 2018.

BACKGROUND: For highly selected patients with peritoneal metastases (PM) from colorectal cancer (CRC), an aggressive surgical approach with intraperitoneal chemotherapy may be beneficial. This management may prolong overall survival, which is well documented by the results of a number of clinical trials. In the Czech Republic, five specialized centers of surgical oncology are able to perform cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC). All of these centers provided accurate information on the number of CRS procedures in 2018 in the PM CRC indication. The estimation of the prevalence of peritoneal metastases from CRC is based on data from the Czech National Cancer Registry. PURPOSE: To determine the number of cytoreductive procedures performed in patients with peritoneal metastases from CRC in the Czech Republic in 2018, and to compare it with the number of patients who could hypothetically benefit from this procedure according to statistical data. RESULTS: Twenty-five CRS/HIPEC procedures were performed on patients with peritoneal metastases from CRC in 2018 in the Czech Republic. However, based on the prevalence of peritoneal metastases from CRC in the Czech Republic, cytoreduction with intraperitoneal chemotherapy (CRS/HIPEC) could probably bring benefit to a minimum of 150 patients a year in the Czech Republic. CONCLUSION: In the Czech Republic in 2018, the cytoreduction and HIPEC procedures for peritoneal metastases from CRC were performed in significantly fewer cases than would correspond to the estimated number of potentially curable patients.To increase the awareness of this issue and improve the number of potentially curative cytoreductive procedures, there will be necessary better awareness and closer cooperation among specialized centers, general surgeons, and clinical oncologists.

[Malignant tumors of the small bowel]. / Maligní nádory tenkého streva.

INTRODUCTION: Malignant tumors of the small bowel are relatively uncommon neoplasms; their incidence is around 1.5 per 100,000 inhabitants in the Czech Republic. METHOD: 104 patients underwent a resection of the small bowel because of a primary or secondary tumor over the 10-year period between 20062015 at the Masaryk Memorial Cancer Institute. Data from these patients was reviewed retrospectively. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: We observed 45 primary and 59 secondary tumors. The group of primary malignancies included 12 adenocarcinomas, 14 cases of GIST and 19 cases of NET. Neuroendocrine tumors showed the best prognosis with a 62% probability of five-year survival. Patients with gastrointestinal stromal tumors had a 39% probability of five-year survival and those with adenocarcinomas had a 32% probability of five-year survival. Secondary tumors were caused mostly by metastatic colorectal carcinoma (22 times), malignant melanoma (11 times) and ovarian cancer (10 times). The probability of five-year survival was 15% in the group of secondary tumors. CONCLUSION: Malignant tumors of the small intestine are rare, but their incidence has increased in the last decades. The main prognostic factors include advancement of the tumor and radicality of surgical resection.Key words: small bowel tumors - adenocarcinoma - sarcoma - NET - GIST - lymphoma.

[Carney triad]. / Carneyho trias.

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.

[Molecular Pathology of Colorectal Cancer, Microsatellite Instability - the Detection, the Relationship to the Pathophysiology and Prognosis]. / Molekulární patologie kolorektálního karcinomu, mikrosatelitová nestabilita - zpusob detekce, vztah k patofyziologii a prognóze.

BACKGROUND: Colorectal carcinoma (CRC) is third most common cancer worldwide with very heterogenous character. In most cases, it is caused by sporadic events leading to disruption of epithelial cells of the colon. The minority evolves from germline mutations associated with hereditary cancer syndromes. Mechanisms leading to mutations of oncogenes, tumour suppressors and genes of DNA repair mechanisms include: 1. chromosomal instability, 2. microsatellite instability and 3. CpG island methylator phenotype. Microsatellite instability (MSI) usually arises from a germline mutation of the component of mismatch repair machinery (MMR) or somatic hypermethylation of the MLH1 promoter. The diagnostic approaches include PCR methods and immunohistochemistry for the detection of the loss of MMR part. The aim of our study was to characterise the cohort of ongoing study of gut microbiome in CRC patients considering MSI. MATERIAL AND METHODS: The consecutive study group consisted of 103 patients diagnosed with CRC. The cohort consisted of 45 women (43.7%) and 58 men (56.3%). Patient age at the time of diagnosis was within the range of 31-83 years (median 66 years). The expression of MLH1, MSH2, MSH6 and PMS2 proteins was detected by immunohistochemical method and the positivity was correlated with the stage and the localization of the primary tumour. RESULTS: The MMR status was determined by immunohistochemical method in 43 (41.7%) from the existing total of 103 patients. MSI was detected in 11 (25.6%) cases while 32 (74.4%) were microsatellite stabile. With the respect to cancer clasification the most cases of MSI was detected in stage II (8 cases; 22.2%). In regard to localization of primary tumour, MSI rather correlates to right site CRC, while microsatellite stable tumours do not show any site preferences. CONCLUSION: Considering low number of MMR status determination in study group, statistic evaluation is inaccurate so far. However there is a trend in our cohort in relation to determination of the portion of MSI in CRC population and also in localization of primary tumour according to literature.Key words: colorectal carcinoma - microsatellite instability - Lynch syndrome The work was supported by the project MEYS - NPS I - LO1413 and AZV 16-31966A. 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.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.

[Circulating Myeloid Suppressor Cells and Their Role in Tumour Immunology]. / Cirkulující myeloidní supresorové bunky a jejich úloha v nádorové imunologii.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogenic population of multipotent progenitors of myeloid lineage. For their immunosuppressive effect, MDSC are responsible for tumour escape from the host immune surveillance. Furthermore, MDSCs support tumour by promotion of angiogenesis and metastasis. Membrane markers of human MDSCs are myeloid markers CD11b and CD13, these cells are HLA-Drlow/- and expression of CD15 or CD14 differentiate them into granulocytic (Gr-MDSCs) and monocytic (Mo-MDSCs), resp. PATIENTS AND METHODS: Using flow cytometry, we investigated Mo-MDSC counts in peripheral blood of non-cancer individuals - control group (n = 61), breast (n = 39) and colorectal (n = 52) cancer patients. These cells were detected as CD45+CD11b+CD33+CD14+HLA-Drlow/- and quantified as percentage of total white blood cells and as absolute count. RESULTS: In control group, circulating Mo-MDSCs was gender-and age-independent and the average value was 1.09% and 0.073 × 109/l. Breast cancer patients had higher circulating Mo-MDSCs compared to control group with average values: 3.57% and 0.229 × 109/l (p < 0.001) and we also observed increase in Mo-MDSC number after granulopoietic growth factors administration (p = 0.043). Colorectal cancer patients had higher average number of circulating Mo-MDSCs compared to control group: 1.71% a 0.125 × 109/l (p = 0.003) and its number did not correlate with tumour clinicopathological stage, localization of primary tumour (colon vs. rectum), site (left vs. right) and microsatellite instability. CONCLUSION: Increased number of MDSCs in circulation and within tumour microenvironment has been associated with immune suppression and tumour progression. Colorectal cancer patients at diagnosis showed higher circulating Mo-MDSCs possibly reflecting immunosuppressive effect of tumour microenvironment. Change of Mo-MDSC number from baseline level need to be evaluated in the context of CRC patients outcome. Recombinant granulopoietic growth factors increase number of circulating Mo-MDSCs and the effect of this phenomenon on cancer prognosis remains to be elucidated.Key words: myeloid-derived suppressor cells - colorectal cancer - breast cancer - immunology - immunosuppression - G-CSF This work was supported by MEYS by NPU I (LO1413), grant AZV 16-31966A and MH DRO 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.Submitted: 11. 3. 2017Accepted: 26. 3. 2017.

[Mixed adenoneuroendocrine carcinoma (MANEC) of the gastrointestinal tract]. / Smísený adenoneuroendokrinní karcinom (MANEC) gastrointestinálního traktu.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumour of the gastrointestinal tract composed of adenocarcinoma and neuroendocrine carcinoma. This pathologic diagnosis was recently defined by the WHO in 2010. The tumour may appear in various levels of the digestive tract including the oesophagus, stomach, colon and appendix. Biological behaviour of MANEC seems to be quite unpredictable and the prognosis uncertain. The disease may also mimic "simple" carcinoma. Only several tens of cases have been reported so far.Our first case was diagnosed as gastric adenocarcinoma mimicking early gastric cancer in a 47 years old male. The second case was diagnosed incidentally in the appendix of a 69 years old female after operation for gynaecologic cancer. The disease was localised in both patients; the patients underwent radical surgical resections.Treatment options have not been standardised yet, but aggressive therapeutic measures are recommended. The patients may benefit from multimodal anticancer therapy.Key words: mixed adenoneuroendocrine carcinoma - MANEC - gastric cancer - appendiceal cancer.

[Current status regarding surgical treatment of pancreatic cancer in the Czech Republic]. / Aktuální stav chirurgické lécby karcinomu pankreatu v Ceské republice.

INTRODUCTION: The aim is to map the current situation in the surgical treatment of pancreatic cancer in the Czech Republic. This information has been obtained from surgical treatment providers using a simple questionnaire and by identifying the so called high volume centres. The information has been collected in the interest of organizing and planning research projects in the field of pancreatic cancer treatment. METHOD: We addressed centres known to provide surgical treatment of pancreatic cancer. A simple questionnaire formulated one question about the total number of pancreatic resections, also separately for the diagnoses PDAC - C25, in the last two years (2014 and 2015). Other questions focused on the use of diagnostic methods, neoadjuvant therapy, preoperative assessment of risks, the possibility of rapid intraoperative histopathology examination, Leeds protocol, monitoring of morbidity and mortality including long-term results, and the method of postoperative follow-up and treatment. ÚZIS (Institute of Health Information and Statistics of the Czech Republic) was addressed with a request to analyze the frequency of reported total numbers for DPE, LPE, TPE and to do the same with respect to diagnosis C 25 for the last two years, available for the entire Czech Republic (2013, 2014). RESULTS: Altogether 19 institutions were identified by the preceding audit, which reported more than 10 pancreatic resections annually; these institutions were addressed with the questionnaire. Sixteen institutions responded to the questions, 13 of them completely. CONCLUSION: The majority of potentially radical surgeries for PDAC in the Czech Republic are carried out at 6 institutions. All of the institutions that participated in the survey collect data about morbidity and mortality and monitor their results. KEY WORDS: pancreas cancer outcomes surgery.

[Von Meyenburg complexes - multiple biliary hamartomas mimicking metastatic liver lesions]. / Von Meyenburgovy komplexy - mnohocetné biliární hamartomy imitující metastatický jaterní proces.

Von Meyenburg complexes are benign liver lesions usually consisting of dilated bile ducts surrounded by fibrous stroma. Their discovery is usually incidental and unsuspected during the early phase of the operative procedure. The sovereign diagnostic method is intraoperative frozen section examination. The complexes are not important as regards their clinical or functional significance. However, this uncommon entity should be taken into consideration in the framework of differential diagnosis of metastatic liver lesions.

[Treatment of gastrointestinal stromal tumors--a comprehensive view of the surgeon]. / Lécba gastrointestinálních stromálních tumoru--komplexní pohled chirurga.

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.

[Pneumoscrotum: uncommon sign in duodenal perforation (a case review)]. / Pneumoskrotum: nezvyklý symptom pri perforaci duodena (kazuistika).

Therapeutic endoscopy is mostly primary method in treatment of biliary tree obstruction with its various complications. A case review describing an oncological pacient examined for obstructive icterus, with recognised pneumoscrotum after endoscopic examination (ERCP). In discussion we try to point out the need of knowledge of clinical examination, clinical signs of duodenal lesions and optimal treatment measures.

[Renal cancer metastasis into common bile duct]. / Metastáza svetlobunecného renálního karcinomu do ductus choledochus.

We present rare case of clear cell renal carcinoma metastasis into common bile duct. It is a 9th case listed on the MEDLINE data base from 1966 to 2010.71-year-old woman underwent right nefrectomy for renal cancer G1 in 1986. She was reoperated in 2006 for relaps in renal bed on the right side. Histological examination confirmed clear cell renal carcinoma again. At present, a new liver metastasis in S 4/5 was detected. During the operation we found first described liver metastasis and second another one in common bile duct with intraluminal growth. Before surgery the patient showed neither clinical nor laboratory marks of biliary obstruction. Even abdominal ultrasound, SONO VUE, CT and body PET were negative. We carried out choledochectomy with hepaticojejunoanastomosis sec Roux and liver metastasis was destructed using radiofrequency ablation.

[Transanal endoscopic microsurgery and its significance in rectal surgery--a review]. / Transanální endoskopická mikrochirurgie a její postavení v chirurgii rekta - review.

Transanal endoscopic microsurgery is a novel endoscopic method. Primarily, it has been developed to manage pathological middle rectum conditions. Over the time, indication criteria for this procedure have become wider and, due to technical progress, more extensive procedures on distal and middle rectum, as well as perirectal transanal procedures, could be performed. At the present time, there are clearly specified technical conditions which limit the procedure's extent, in particular the distance from the anus and the extent of rectal circumference affection. At the same time, when the method started to be used for surgical management of malignant tumors, a question arised, i.e. when the use of surgical rectoscope remains beneficial for a patient and when this method shows inferior long-term outcomes, considering the rate of local relapses and long- term survival rates. Based on the 2007-2010 literature review, the author aims to present principles to be used in the process of making a decision when the miniinvasive approach should be used and, vice versa, in which conditions the benefit of radical surgery has been demonstrated.

[Use of local hemostyptic drugs in liver resections]. / Vyuzití lokálních hemostyptik pri jaterních resekcích.

INTRODUCTION: Bleeding during and following liver resection continues to be an object of surgeon's attention and a potential source of significant morbidity. Topical hemostatic agents are used during surgical intervention when conventional methods are not sufficient because of the site of surgery or degree of bleeding. A variety of agents with different effects is now available. AIM: To verify the efficacy and safety of cellulose based local hemostat during liver resections. METHODS: In 67 cases of liver resection the surface was covered by Traumacel TAF net which was left in place. RESULTS AND CONCLUSION: There were no postoperative bleeding in this group of patients. No other serious complication has been observed. Traumacel is a safe and effective local hemostat during liver resections.

Micro-RNAs miR125b and miR137 are frequently upregulated in response to capecitabine chemoradiotherapy of rectal cancer.

There is increasing evidence that some microRNAs change their levels in reaction to xenobiotic challenge. The aim of this study was to test the possible involvement of micro-RNAs in response to standard anticancer treatment. Tumor biopsies from 35 patients with rectal cancer before therapy and parallel tumor biopsies from 31 patients two weeks after starting preoperative capecitabine chemoradiotherapy were taken. The expression levels of single miRNA species were measured using TaqMan Micro-RNA assays after reverse transcription from isolated total RNAs. Many micro-RNAs (miR10a, miR21, miR145, miR212, miR339, miR361) responded to chemoradiotherapy in individual tumor samples, but there was profound intertumoral variability. However, other two micro-RNAs miR125b, miR137 showed a significant increase in median expression levels after starting therapy in most samples. Moreover, our results for the first time show that higher induced levels of miR125b and miR137 are associated with worse response to the therapy.

Use of radiofrequency ablation in the treatment of malignant liver lesions.

BACKGROUND/AIMS: The authors present their experience with the option of using radiofrequency ablation (RFA) in the treatment of malignant focal liver lesions. METHODOLOGY: In a prospective study conducted in the period from 2002-2005, 60 patients were treated using RFA during a total of 72 sessions and treating 108 lesions of various size, number and localisation. The method of RFA was applied either percutaneously under computed tomography (CT) or ultrasonographic (USG) navigation (22 patients) or surgically--during opened laparotomy or laparoscopy (42 patients). RESULTS: Median observation time was 12.7 months (with the range 3-36 months). Authors did not observe any serious complications after RFA treatment in the study population. Median time of local recurrence in the ablated lesion position was 13.5 months in the observed population, median time of metastatic progression in the residual liver parenchyma was 12 months, and overall median survival was 22 months. Percutaneous RFA application demonstrated significantly worse results when compared with surgical application in previously the mentioned parameters. Lesions larger than 3cm in diameter also showed statistically more frequent local recurrence. CONCLUSIONS: RFA is appreciated as minimally invasive method of treatment for liver malignancies with promising perspectives of therapeutic effects.

[A role of PET and CT examinations in the management of malignant disorders of the large intestine and rectum--a review]. / Role PET a CT vysetrení v managementu lécby zhoubného onemocnení tlustého streva a konecníku--review.

Current treatment methods of solid malignant disorders, in particular, depend, more and more, on perfection of paraclinical examination methods. Clinical examination conclusions, supported by imaging findings, determine the treatment strategy. Radical surgical procedures still remain the only treatment modality resulting in a patient's recovery. Correct timing of the procedure with respect to other therapeutical modalities, has a major positive impact on the treatment success rates. Ongoing improvements of imaging methods and development of new methods introduced in our clinical practice have made individual patient treatment plans possible. The overview includes brief history of the imaging techniques development, as well as current situation in the large intestinal and rectal malignancies in various disease stages, supported by the most significant of the few presented studies.

Preoperative radiotherapy and concomitant capecitabine treatment induce thymidylate synthase and thymidine phosphorylase mRNAs in rectal carcinoma.

This work is intended to study the effect of preoperative capecitabine and radiotherapy treatment on the levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) mRNAs in rectal carcinoma. 55 patients with locally advanced rectal carcinoma (cT3-4, N0, M0 or cT2-4,N+, M0) were treated with capecitabine 825 mg/m2 twice a day and pelvic radiotherapy 1,8 Gy daily up to cumulative dose of 45 Gy, boosting up to 50,4 Gy. Patients underwent surgery 6th week after the completion of chemoradiotherapy. Biopsies of rectal carcinoma were taken before starting therapy and 14 days after its cesation. Biopsies were examined for TS, DPD and TP mRNA levels. CEA in serum was examined to monitor relapses. Both TP and TS mRNA increase two weeks after starting therapy (p<0,001). TP mRNA median levels were elevated 2,3x after starting therapy. Moreover responders exhibit 1,5x higher induction than non-responders both before and after starting therapy, but difference is significant before therapy only (p=0,017). Non-responders have most frequent TS induction. Complete remission was observed in 17% and substantial responses with microscopic residuum only in additional 19% of cases were achieved. The pathologic downstaging rate was 76%. Our data show that TS and TP mRNA are induced by preoperative chemoradiotherapy in both responders and nonresponders. TP induction is in accordance with the expected role of TP in the activation of capecitabine and the known promoting role of TP in tissue fibrosis frequently associated with tumor regression.

[An unusual cause of the chronic ileus state--the absence of the intestinal wall muscularis layer]. / Neobvyklá prícina chronického ileózního stavu--absence muscularis strevní steny.

In this study the authors describe a rare histological finding in the resected small intestine, which was a cause of continuous ileal difficulties in a young female patient, and which increased in their intensity and finally resulted in an acute state which had to be solved by an urgent surgical procedure. The situation was defined as "absence of the muscularis layer" of the intestinal wall by a pathologist. The pathologist also stated that he had never come across such a case, neither in our literature, nor in the foreign one and that the condition was diagnosed with difficulties when using a standard visualization examination methods.