Peritoneal carcinomatosis of colorectal origin treated by cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy at the Bulovka University Hospital.

INTRODUCTION: Peritoneal carcinomatosis (PK) of colorectal origin is a malignant tumour of the peritoneum caused by spreading of colorectal carcinoma (KRK) over the peritoneal surface of the abdominal cavity and its organs. PK occurs as a synchronous tumour in 1520% of patients, and as metachronous disease in 2550% of patients. METHODS: A group of 66 patients operated on for PK was retrospectively evaluated; 18 patients were excluded due to insufficient data. We evaluated 48 patients in total (22 men and 26 women) with mean age of 58 and 53 years, respectively; 12 patients (25%) were aged over 65 years. The patients were operated on between 2000 and 2019 using the Sugarbaker´s method of maximal cytoreduction (CRS) + HIPEC (Hyperthermic Intraoperative Peritoneal Chemotherapy). We evaluated the length, median survival, the incidence of complications and lethality in relation to the Peritoneal Carcinoma Index (PCI) and the Completeness of Cytoreduction (CC) score. The patients were divided into two subgroups according to the PCI score (012 and >12, respectively) and the CC score (CC 01 and CC 23, respectively). RESULTS: The mean survival was 26.3 months in the group with PCI up to 12 and 21.4 months in patients with PCI above 12 (p=0.02). In the group with CC 01 the mean survival was 27.1 months, while in the patients with the CC 23 it reached 12.6 months (p=0.06). The morbidity rate requiring an intervention was 18.7% and the lethality rate was 6.25% in the entire group. The median survival of the entire group was 22 months (1334 months). CONCLUSION: Literary references and our results are comparable, confirming the high efficiency of this method both in our country and worldwide. The use of CRS and HIPEC, associated with acceptable mortality and morbidity in selected patients with PK of colorectal origin, results in a significant extension of overall survival (OS).

Pulmonary metastases in pseudomyxoma peritonei - case report and review of the literature.

Pseudomyxoma peritonei is a rare disease caused by dissemination of cancer forming mucous and gelatinous masses in the peritoneal cavity. Local recurrence is frequent; however, dissemination outside the peritoneal cavity is rare.  Case report: We present the case report of a female patient treated for bilateral pulmonary metastases from pseudomyxoma peritonei. We removed 1 metastasis from her left lung and 12 metastases form her right lung. The patient remained in a good clinical state; however, additional lung metastases developed, as well as a metastasis in L2 vertebra for which the patient underwent a surgical procedure. Conclusion: Cytoreductive surgeries for intrathoracic involvement in pseudomyxoma peritonei with additional hyperthermic cytostatic intrapleural lavage in case of pleural involvement can lead to a longer lifespan in indicated patients.

Pseudomyxoma peritonei (PMP) and its therapy - 20 years experience of a single surgical department.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare malignant disease with various grades of malignancy, producing mucinous and gelatinous masses. The origin of PMP is usually connected with the rupture of appendiceal mucinous tumours, other mucinous tumours of the gastrointestinal tract or of the ovary. The staging of this disease is determined by the PCI score (peritoneal cancer index), and the efficiency of surgical procedure by the CC score. Clinical presentation is very variable and depends on the stage of the disease. Many patients are asymptomatic with a minimal clinical finding, presented only with abdominal discomfort. A typical finding of the “jelly belly“ syndrome expands with progression of the disease. The diagnosis consists in preoperative determination of the tumour characteristics and PCI based on imaging methods, especially CT imaging. METHODS: The Sugarbaker technique of complete tumour removal or the so-called cytoreductive surgery (CRS) was used, including hyperthermic intraperitoneal chemotherapy (HIPEC) or alternatively early postoperative intraperitoneal chemotherapy (EPIC). We performed retrospective evalu-ation of 73 patients with pseudomyxoma peritonei undergoing surgery, 39 males and 34 females, mean age 50.6 and 56.4 years, respectively. Surgical revision was performed in 18 patients, 14 males and 4 females. The mean age of this group was 48.8 for the males and 47 for the females. The surgical procedures were performed between 1999 and 2018. Survival rates, median survival, complications based on Clavien-Dindo classification, lethality rates, and PCI and CC scores were assessed in the patient group. RESULTS: 96 surgeries were performed in 73 patients with pseudomyxoma peritonei at our surgical department between 19992018. The surgery had to be repeated in 18 patients (24.6%). High grade (HG) pseudomyxoma was diagnosed in 29 patients (39.7%), and low grade (LG) pseudomyxoma in 44 patients (60.3%). Overall morbidity was 27.3%, and the mortality rate was 5.4%. The mean overall survival (OS) was 139.5 months in the LG pseudomyxoma group and 71.5 months in the HG pseudomyxoma group. Median survival was 86 months in the entire group and 72 in the HG pseudomyxoma group; the median was not reached in the LG pseudomyxoma group. CONCLUSIONS: Results in the literature and our results are comparable, confirming the high efficiency of this method both in the world and in the Czech republic. The results indicate a highly statistically significant improvement of the OS with acceptable mortality and morbidity. These results confirm this method as a gold standard therapy for selected patients.

Clinical and microbiological characteristics of Clostridium difficile infection in children hospitalized at the Departement of Paediatric Infectious Diseases in Brno between 2013 and 2017.

AIMS: Clostridium difficile (C. difficile) plays a minor but important role in paediatrics. The aims of this study were to objectivise data, to show their significance in clinical practice, and to present our experience with the treatment of paediatric patients. MATERIALS AND METHODS: A retrospective study was conducted in patients (0-19 years of age) hospitalized for Clostridium difficile infection (CDI) in the Department of Paediatric Infectious Diseases, University Hospital in Brno between 2013 and 2017. Each patient was tested using a two-step diagnostic screening algorithm including immunochromatography and polymerase chain reaction assays. RESULTS: Thirty-five patients with a median age of 10.3 years (range 1-17.5 years) were enrolled in the study. Almost 70% of patients were aged between 6 and 19 years. No risk factor was identified in one patient, 41.6% of cases were patients with malignancy or inflammatory bowel disease, and 2.5% of patients had short bowel syndrome. After targeted CDI treatment, the median time to resolution of diarrhoea was 2.5 days. Metronidazole was used in more than half of cases. Five patients received fidaxomicin, which was well tolerated. Metronidazole failed in three cases. Recurrence after incomplete treatment with metronidazole occurred in one patient. Health care-associated CDI was recorded in 86% of cases. Recurrent CDI was reported in four children (two with malignancy, one with inflammatory bowel dissease, and one with short bowel syndrome). CONCLUSIONS: The course of CDI is generally mild in the paediatric population. CDI without a risk factor is rare. Paediatric patients respond well to metronidazole. Fidaxomicin was well tolerated by all patients. We prefer the treatment with fidaxomicin in high-risk groups (immunocompromised condition, inflammatory bowel disease, and short bowel syndrome).

Molecular and IHC analysis of head and neck carcinomas associated with HPV infection.

Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens - tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chí-x2 test.HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24). Keywords: head and neck carcinomas, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf.

Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

AIM: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression. RESULTS: Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each). CONCLUSION: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.

Postoperative radiochemotherapy with weekly cisplatin in patients with head and neck cancer single-institution outcome analysis.

The objective of this study was to evaluate the feasibility, toxicity and efficacy of postoperative radiochemotherapy with weekly cisplatin in locoregionally advanced or high risk head and neck cancer in a single institutional setting. Patients with head and neck cancer of stage III/IV or patients with insufficient margins of resection were included in the study. Radiotherapy consisted of 70 Gy/ 7 weeks/ 35 fraction after R1/2 resection and 60-64 Gy/ 6-6,5 weeks/ 30-32 fraction after R0 resection, respectively. All patients received concurrent cisplatin 40 mg/m2 weekly. Between 7/2002 and 12/2008, 100 consecutive patients [WHO ≤ 2, male to female ratio 84/16, median age 54 years] were treated. Tumors of the oropharynx were the most frequent (49%) and stage IV was predominant (86%). 96% patients received the full radiation treatment as planned, median total tumor dose was 66 Gy. Omission of weekly cisplatin had been occurring frequently, the most frequent reason for its early cessation were hematological toxicities (34%). Grade 3/4 mucosal toxicity developed in 32%. No death was observed during the treatment. The late toxicities were acceptable, predominantly subcutaneous fibrosis and xerostomia in most of the cases. We recorded six cases of osteonecrosis. Two and half year overall survival, locoregional control, time to progression and disease free survival were 64%, 88%, 79% and 59%, respectively. Postoperative radiochemotherapy with weekly cisplatin is toxic, but tolerable and highly effective in terms of locoregional control and survival. Multivariete analysis revealed that the only prognostic factor for survival was primary surgery at the University centre.

[Visceral leishmaniasis (two case reports)]. / Viscerální leishmanióza (dve kazuistiky).

Two cases of imported visceral leishmaniasis are described. The first patient was a 32-year-old Czech man who developed leishmaniasis 5 months after a holiday in Italy (Bibione). The second patient was a 62-year-old Czech man who developed leishmaniasis 18 months after visiting Croatia (Makarska); the disease began after a course of chemotherapy due to metastasizing testicular tumor. Both patients were successfully treated with amphotericin B lipid complex (Abelcet). Difficulties in establishing the correct diagnosis of visceral leishmaniasis are discussed.

Definitive radiochemotherapy with weekly cisplatin in patients with head and neck cancer; single institution outcome analysis.

PURPOSE: The objective of this study was to evaluate the feasibility, toxicity and efficacy of definitive radiochemotherapy with weekly cisplatin in head and neck cancer in a single institutional setting. METHODS: Previously untreated patients with stage II-IV head and neck cancer were included. Radiotherapy consisted of 70 Gy/7 weeks/35 fractions. All patients received concurrent cisplatin 40 mg/m(2) weekly. RESULTS: Between 2/2002 and 8/2009, 148 consecutive patients (WHO ≤ 2, male to female ratio 6/1, median age 56 years) were treated. The mean follow-up was 40 months. Tumors of the oropharynx were the most frequent (46%) and stage IV predominated (80%). Eighty-nine percent of the patients had received the full radiation treatment as planned. Omission of weekly cisplatin occurred frequently, mainly because of hematological toxicity. Only 64% of the patients completed at least 5 cycles of chemotherapy. Grade 3/4 mucosal toxicity developed in 32% of the patients. The late toxicities were acceptable: 74% of the patients were able to eat solid food during the 1st post-treatment year, 4 patients were not able to swallow at all during the 1st post-treatment year, requiring thus permanent feeding tube. Five cases of osteoradionecrosis of the mandible were reported. Three-year overall survival, locoregional control, time to progression and disease free survival were 34, 60, 52 and 29%, respectively. CONCLUSION: Definitive radiochemotherapy with weekly cisplatin was toxic, with high rate of morbidity and mortality in this patient population. Five weekly cycles of 40 mg/m(2) cisplatin seem to be the dose limit for most patients. Three-year survival was significantly reduced despite the promising high initial response and locoregional control.

Oncology wounds - recommendations for care based on multidisciplinary cooperation.

BACKGROUND: Oncology wounds and wounds of other etiology are rare but serious complications, which significantly impair patients quality of life. Preventive and curative interventions and education of healthcare personnel and patients reduce the risk of either their occurrence or their impact and consequences. A working group of authors from professional groups (the Supportive Care Group of the Czech Society for Oncology, the Czech Society for Wound Healing, the Society for Radiation Oncology, Biology and Physics, and the Czech Nurses Association) prepared recommendations for care. A comprehensive approach to the treatment of oncological wounds, including symptomatic treatment of associated healing complications, prevention, early detection, interdisciplinary cooperation and education are essential to deal with wounds related to chemotherapy administration, radiotherapy and oncological treatment in general. The proper choice of local care products and the eventuality of active oncological treatment are important elements of care in ulcerating tumors. PURPOSE: A basic summary of recommended interventions to prevent and treat oncology wounds in daily practice, defined based on expert societies guidelines, trials and literature data, proven practice and on the consensus opinions of the authors group members. The recommended procedures contribute to the reduction of the development, severity and consequences of oncological wounds and wounds of other etiology in oncological  patients.

Oral cavity complications in oncological and hemato-oncological patients.

BACKGROUND: Oral cavity injuries are very significant complications in the treatment of oncological and hemato-oncological patients. Preventive and curative interventions and patient education reduce the risk of complications and their consequences. A working group of authors from professional groups prepared recommendations for care. PURPOSE: A basic summary of recommended interventions to prevent and treat oral cavity injuries in daily practice, defined on the basis of expert societies guidelines, trials, literature data and proven practice and on the consensus opinions of the authors group members. RESULTS: Preventive measures and patient education are essential in the approach to dealing with oral injuries in chemotherapy, radiotherapy, risky targeted treatment and osteonecrosis of the jaw. Local care products are an important element of care, in case of infections, their antimicrobial action is essential, in case of graft-versus-host disease or in connection with targeted oncological therapy, corticoids are used. CONCLUSION: The recommended procedures contribute to the reduction of the development, severity and consequences of oral complications in oncological and hemato-oncological patients.

Rectal carcinoma after radiotherapy for cervical carcinoma in patients with a family history of colorectal carcinoma: report of two cases.

Rectal carcinoma is a rare, but well documented late complication of pelvic irradiation. Little is known about the factors predisposing to the development of radiation-associated rectal carcinoma. We present two patients who developed rectal carcinoma 17 and 26 years after radiotherapy for carcinoma of the uterine cervix. In one patient, mutation in exon 4 of the hMLH1 gene was detected. Radiation-associated rectal carcinoma represents a rare late toxicity of radiotherapy for cervical carcinoma that may occur in patients with a family history of colorectal carcinoma, including hereditary non-polyposis colorectal cancer.