Appendiceal tumors and pseudomyxoma peritonei: current recommendations for clinical practice.

Appendiceal tumors and pseudomyxoma peritonei (PMP) are rare tumors. Perforated epithelial tumors of the appendix are the most common source of PMP. This disease is characterized by the presence of mucin of varying degrees of consistency, partially adherent to the surfaces. Appendiceal mucoceles themselves are also very rare and usually their treatment involves only a simple appendectomy. The aim of this study was to provide an up-to-date review of the recommendations for the diagnosis and treatment of these malignancies according to the current guidelines of The Peritoneal Surface Oncology Group International (PSOGI) and the Blue Book of the Czech Society for Oncology of the Czech Medical Association of J. E. Purkyne (COS CLS JEP).

Hyperthermic intraoperative intrapleural chemotherapy and surgical cytoreduction as part of multimodal treatment of malignant pleural mesothelioma - case report M. Szkorupa1, D. Klos1, J. Chudacek1, J. Hanuliak1, M. Stasek1, O. Fischer2, R. Lemstrova3.

Malignant pleural mesothelioma is one of the most aggressive malignancies with a very poor prognosis. Multimodal treatment consisting of three modalities - chemotherapy, radiotherapy and cytoreductive surgery is optimal. The use of new therapeutic modalities, such as hyperthermic intraoperative intrapleural chemotherapy or photodynamic therapy can improve the current results of mesothelioma treatment. Combined hyperthermic intraoperative chemotherapy and cytoreductive surgery as part of multimodal therapy of malignant mesothelioma has been used since 2017 at the 1st Department of Surgery of University Hospital Olomouc. The authors report the case of a 47-year-old man with malignant epithelioid mesothelioma of the left pleural cavity. Following neoadjuvant chemotherapy, this patient underwent extrapleural pneumonectomy with intraoperative intracavitary hyperthermic chemotherapy. The postoperative period was complicated by circulatory instability and later by tension fluidothorax with signs of heart failure. Currently, 8 months have elapsed from the surgery and the patient remains without any signs of recurrence.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216.

The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive tumor.

[Evaluation of Anti-cancer Therapies with Reimbursement Limited to Comprehensive Cancer Centres Using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale]. / Hodnocení klinického benefitu protinádorových léku limitovaných na komplexní onkologická centra podle metodiky ESMO-MCBS.

BACKGROUND: The costs of oncology treatments are increasing, due to the rising prevalence of malignant diseases and the introduction of expensive novel anti-cancer agents. The new European Society for Clinical Oncology (ESMO) has recently developed a new parametric system to evaluate the clinical benefit of drugs. The Magnitude of Clinical Benefit Scale (ESMO-MCBS) compares the contribution of a novel drug based on overall and progression-free survival and quality of life with those of current treatment options. MATERIAL AND METHODS: An expert group of the Czech Oncological Society conducted an assessment based on published data and an ESMO-MCBS methodology for antineoplastic agents used for the treatment of solid tumors with limited reimbursement to Comprehensive Cancer Centers. We evaluated drugs categorized as "S" that were eligible for public health insurance as of January 1, 2017. RESULTS AND CONCLUSION: The ESMO-MCBS score is a promising new parameter for the evaluation of new anticancer drugs. The ESMO-MCBS method for assessing the clinical benefit of drugs is simple, robust, and reproducible. The advantage of the assessment is that it is not based on a single index but rather combines several dimensions of drug performance. This parameter will be gradually added to Czech cancer guidelines. Scores obtained in the majority of cases correspond to the observed benefit of a drug in routine clinical practice.Key words: tumors - farmacotherapy - assesment study as a subject - survival - protocols of anti-cancer therapy 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: 3. 5. 2017Accepted: 20. 6. 2017.