Urogenital dysfunction in patients after miniinvasive restorative low anterior resection with total mesorectal excision.

Introduction: Over the last decades outcomes for rectal cancer surgery have improved, with increasing survival rates. Nevertheless, functional disorders are still frequent. Aim: To evaluate sexual and urinary outcomes of miniinvasive total mesorectal excision (TME). Material and methods: Between March 2016 and June 2018 patients with rectal cancer who underwent miniinvasive TME with a sphincter-saving procedure were enrolled. The questionnaires were completed before therapy, and 6, 12, and 24 months after stoma closure. We used the Female Sexual Function Index (FSFI), the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function questionnaire (IIEF). Results: Ninety-eight patients completed the questionnaires. Only patients who underwent laparoscopic (39) or robotic TME (27) were enrolled. The characteristics and surgical outcomes did not differ significantly between these groups. The IPSS between the groups was comparable before and after the operation with no significant difference, increased at 6 months and then decreased consecutively. In comparison with baseline, IPSS was significantly lower in the laparoscopic and robotic groups at 6 months and was comparable to baseline at 24 months in both groups. Oppositely, the IIEF was significantly lower at 6 months after ileostomy closure in the robotic group (p < 0.05), but not in the laparoscopic group (p = 0.59) and both returned to baseline at 24 months. FSFI was significantly lower in the laparoscopic group (p = 0.017) 6 months after surgery and returned to baseline at 24 months in both groups. Conclusions: Laparoscopic and robotic TME showed similar functional results 2 years after stoma resection.

Patients with metastatic renal cell carcinoma treated with cabozantinib in the Czech Republic: analysis of four cancer centers.

AIM: The aim of this study was to retrospectively analyze treatment outcomes and tolerance in patients in whom cabozantinib was used after previous targeted therapy. PATIENTS AND METHODS: Cabozantinib was administered in dose 60 mg/day, a subset of patients received initial dose of 40 mg/day. The treatment was administered until to progression or unacceptable toxicity. CT scans were assessed according to the RECIST 1.1 and toxicity of treatment was assessed based on the CTCAE (version 4). Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. All statistics were evaluated at the significance level alpha = 0.05. RESULTS: 54 patients with metastatic renal cell carcinoma (mRCC) were evaluated. Median PFS in all patients treated with cabozantinib was 9.3 months (95% CI 5.3 - 13.3). One-year survival was 85.2% (95% CI 72.9 - 93.4%). Treatment response was observed in 45.9% of cases, including one complete remission. Cox regression analysis demonstrated that presence of subsequent treatment was the only factor with a significant effect on OS (P=0.008). Adverse events occurred in 88.9% of patients, grade 3 - 4 in 46.3%. CONCLUSION: The analysis of our cohort of patients treated with cabozantinib in the second or higher lines of treatment showed that cabozantinib represents an effective and safe therapy and contributes to longer survival of our mRCC patients.

Intraoperative fluorescence angiography and risk factors of anastomotic leakage in mini-invasive low rectal resections.

BACKGROUND: One of the prerequisites for proper healing of the anastomosis after a colorectal resection is adequate blood supply to the connected intestinal segments. It has been proposed that adequate visualization of the blood flow using indocyanine green (ICG) could lead to the reduction in the incidence of anastomotic leakage (AL). The aim of this study was to assess the effectiveness of intraoperative fluorescence angiography (FA) in decreasing the incidence of AL after minimally invasive low anterior resection (LAR) with total mesorectal excision (TME) in rectal cancer patients and to determine predictors of anastomotic leak. METHODS: From August 2015 to January 2019, data from 100 patients who underwent mini-invasive TME for rectal cancer using FA with indocyanine green (ICG) were prospectively collected and analyzed. They were compared with retrospectively analyzed data from a historical control group operated by one team of surgeons before the introduction of FA from November 2012 to August 2015 (100 patients). All patients from both groups were operated sequentially in one oncological center in Nový Jicín. RESULTS: The incidence of AL was significantly lower in the ICG group (19% vs. 9%, p = 0.042, χ2 test). In fifteen patients in the ICG group (15%), the resection line was moved due to insufficient perfusion. Using Pearson's χ2 test, diabetes (p = 0.036) and application of a transanal drain (NoCoil) (p = 0.032) were identified as other risk factors (RFs) for AL. CONCLUSION: The use of ICG to visualize tissue perfusion in low rectal resections for cancer can lead to a reduction of AL.

The significance of intraoperative fluorescence angiography in miniinvasive low rectal resections.

INTRODUCTION: Anastomotic leak is a very serious complication in colorectal surgery. Tissue perfusion of the anastomosis plays an integral role in its multifactorial etiology. Fluorescence angiography using indocyanine green allows visualization of perfusion in real time. AIM: To evaluate the effectiveness of intraoperative fluorescence angiography as a tool to decrease the incidence of anastomotic leak after laparoscopic or robotic low resection of the rectum for cancer. MATERIAL AND METHODS: Intraoperative fluorescence angiography was performed sequentially in 50 patients during low rectal resection for cancer with total mesorectal excision, primary anastomosis and protective ileostomy using laparoscopic or robotic technique. The results were compared to a historical control group of 50 patients with the same procedure without the use of fluorescence angiography. RESULTS: The patient sets were comparable in basic demographic and clinical parameters. Intraoperative visualization of perfusion by fluorescence angiography was achieved in all patients without unwanted side-effects. In 6 (12%) patients, the resection line was adjusted based on the fluorescence angiography. The incidence of anastomotic leak was insignificantly lower in the group with fluorescence angiography (18% vs. 10%), which led to significantly shorter hospital stay. Other postoperative complications were comparable between the two groups. CONCLUSIONS: Fluorescence angiography using indocyanine green is a safe and effective method with the potential of reducing anastomotic leak during minimally invasive low resection of the rectum for cancer.

The expression of PD-L1 in patients with castrate prostate cancer treated with enzalutamide.

PURPOSE: The purpose of our retrospectively study was to evaluate the PD-L1 expression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: A total of 33 patients with mCRPC were treated with enzalutamide. All patients were previously treated by one or two lines of chemotherapy. Enzalutamide was administered in the standard dose (160 mg orally once daily as four 40 mg capsules). No corticosteroids were concomitantly administered. PD-L1 expression was determined semiquantitavely by immunohistochemistry. RESULTS: Enzalutamide was well tolerated with predominantly G1-2 toxicity. G3-4 anaemia was found in 6 patients and G3-4 thrombocytopenia in 2 patients. One patient had cerebral hemorrhage. The median progression free survival (PFS) was 7.0 months (95% CI 6.1-7.9). The median overall survival (OS) was 8.4 months (95% CI: 5.1-11.7). The shorter OS was noted in the subgroup of patients with decreasing hemoglobin levels during enzalutamide treatment with hazard ratio (HR) 0.155 (95% CI 0.053-0.449) and in patients with Gleason score 8-10 with HR 0.334 (95% CI 0.12-0.927) according to the regression analysis. All tissue samples were scored as negative in the detection of PD-L1. CONCLUSIONS: The expression of PD-L1 in prostate cancer cells as potential new predictive biomarker was not confirmed. Further studies are needed to clarify this topic.

The prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression in patients with locally advanced rectal adenocarcinoma.

PURPOSE: To evaluate the prognostic effect of neoadjuvant chemoradiotherapy on the change of programmed death ligand 1 (PD-L1) expression in patients with locally advanced rectal adenocarcinoma, by comparing PD-L1 expression in pretreatment biopsies and PD-L1 expression in pathological specimens after neoadjuvant chemoradiotherapy. METHODS: A total of 25 patients with rectal adenocarcinoma were evaluated. Patients were treated by neoadjuvant chemoradiotherapy (radiotherapy:44Gy normofraxionation; chemotherapy: capecitabine 825 mg/m2 in two daily doses). Surgery was performed 6-8 weeks after the chemoradiotherapy completion. PD-L1 expression was determined in endoscopic biopsies and in resected specimens with immunohistochemistry. RESULTS: All 25 patients received radiotherapy without interruption, while concomitant chemotherapy was discontinued prematurely in one patient because of hematological toxicity. In 13 patients sphincter-saving surgery were performed, and 12 patients underwent rectum resection. Downstaging was noticed in 17 patients. Stable disease was found in 5 patients, and progression in 3. The median disease free survival (DFS) was not reached. Three-year DFS was 54.3% (95% CI 34.3-74.2). The median overall survival (OS) was 60 months (95% CI 48-60). Three-year OS was 75 % (95% CI 57.7-92.3). No PD-L1 expression was noticed in pretreatment biopsy and in resected tissue after chemoradiotherapy. CONCLUSION: No prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression was demonstrated in patients with locally advanced rectal adenocarcinoma.

Carboplatin with intravenous and subsequent oral administration of vinorelbine in resected non-small-cell-lung cancer in real-world set-up.

OBJECTIVES: Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with Stage IIA, IIB or IIIA non-small cell lung cancer (NSCLC) after complete resection. Results obtained for Stage IB were not conclusive. While vinorelbine plus cisplatin is the preferred choice after resection, combining vinorelbine with carboplatin promises improved compliance and delivery of drugs due to lower toxicity. We evaluated the impact of this option on treatment compliance and survival under real-world conditions. MATERIAL AND METHODS: A prospective, single-arm, multicenter, non-interventional study evaluated the tolerability, dose intensity and survival resulting from adjuvant use of intravenous carboplatin (AUC 5 on day 1) with vinorelbine administered both intravenously (25 mg/m2 on day 1) and orally (60 mg/m2 on day 8) within four cycles of 21 days each. A total of 74 patients with a median age of 64 years were observed. RESULTS: The mean number of accomplished cycles was 3.78, and 62 patients (83.7%) completed all four planned cycles. Relative dose intensity for carboplatin was 88.9%, for intravenous vinorelbine 93.1%, and for oral vinorelbine 83.2%. Median follow-up was 4.73 years. Median disease-specific survival (DSS) was 7.63 years, median overall survival (OS) was 5.90 years, median disease-free survival (DFS0) was 4.43 years, and five-year survival was 56.2%. TNM stage of disease significantly affected DSS and OS. Favorable survival was observed in females, nonsmokers, patients aged over 65 years, patient with prior lobectomy, patients with tumor of squamous histology, and those who finished the planned therapy, but the differences were non-significant. CONCLUSION: Adjuvant carboplatin with vinorelbine switched from intravenous to oral administration was shown to be a favorable regimen with regard to tolerability and safety. Compliance to therapy was high, and survival parameters were promising, showing that applied regimen can be another potential option for adjuvant chemotherapy in patients with NSCLC.

The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma.

AIM OF THE STUDY: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival.

Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum.

BACKGROUND: MicroRNAs (miRs) represent a distinct class of posttranscriptional modulators of gene expression with remarkable stability in sera. Several miRs are oncogenic (oncomiRs) and are deregulated in the pathogenesis of breast cancer and function to inhibit tumor suppressors. Routine blood monitoring of these circulating tumor-derived products could be of significant benefit to the diagnosis and relapse detection of early-stage breast cancer (EBC) patients. METHODS: Aim of this project was to determine expression of miR-155, miR-19a, miR-181b, miR-24, relative to let-7a in sera of 63 patients with EBC and 21 healthy controls. Longitudinal multivariate data analysis was performed to stochastically model the serum levels of each of the oncomiRs during disease phases: from diagnosis, after surgery, and following chemo/radiotherapy. Moreover, this analysis was utilized to evaluate oncomiR levels in EBC patients subgrouped using current clinical prognostic factors including HER2, Ki-67, and grade III. RESULTS: EBC patients significantly over-express the oncomiRs at the time of diagnosis. Following surgical resection the serum levels of miR-155, miR-181b, and miR-24 significantly decreased (p = 1.89e-05, 5.41e-06, and 0.00638, respectively) whereas the miR-19a decreased significantly after the therapy (p = 0.00869). Furthermore, in case of high-risk patients serum levels of miR-155, miR-19a, miR-181b, and miR-24 are significantly more abundant in comparison to low-risk group (p = 0.026, 0.02567, 0.0250, and 0.00990) and show a decreasing trend upon therapy. CONCLUSIONS: OncomiRs are significantly more abundant in the sera of EBC patients compared to controls at diagnosis. Differences in oncomiR levels reflecting EBC risk were also observed. Testing the oncomiRs may be useful for diagnostic purpose and possibly also for relapse detection in follow-up studies of EBC.

Laparoscopic abdominoperineal resection with intraoperative radiotherapy for locally advanced low rectal cancer.

AIMS: Intraoperative radiotherapy (IORT) for locally advanced rectal cancer as an integral part of multimodal treatment, may lead to reduced local recurrence but it is not routinely used. The aim of this paper is to describe our experience with IORT in the treatment of patients with locally advanced adenocarcinoma of the lower third of the rectum. MATERIAL AND METHODS: Laparoscopic abdominoperineal amputation of the rectum with intraoperative radiotherapy was performed on 17 patients, 13 men and 4 women, median age 64 years (49-75 years) between 2010-2011. All patients underwent complete therapy according to the treatment protocol. RESULTS: In one patient, the laparoscopic procedure had to be converted to an open resection. The duration of the surgical procedure with IORT was 185 to 345 min (median 285 min). In 14 cases, the intraoperative dose was 10 Gy and in two patients a dose of 12 Gy was used. There were no severe intraoperative complications. Blood loss ranged from 30 to 500 mL (median 100 mL). There were postoperative complications in 4 patients (23.5%); 2 necessitated surgical reintervention (11.8%). The duration of postoperative hospitalization was 6 to 35 days (median 7 days). In the follow-up of 2 to 16 months (median 12 months), no local recurrence or disease generalization have been found to date. CONCLUSIONS: The results show the technical feasibility of laparoscopically assisted abdominoperineal amputation of the rectum in combination with IORT in the treatment of locally advanced rectal carcinoma with an acceptable risk of postperative complications.

Evaluation of laparoscopic resection of colorectal carcinoma from the viewpoint of molecular biology.

AIM: Detection of the possible impact of surgical management on the occurrence of minimal residual disease (MRD) in patients with colorectal carcinoma (CRC) in bone marrow samples, portal and peripheral blood samples. Comparison of MRD prevalence in patients with laparoscopic resection of CRC and those with open colorectal resection. Assessment of the potential impact of MRD on the relapse of the disease and overall survival of patients. MATERIAL AND METHODS: The study included 124 patients with primary CRC without proven distant metastases indicated for elective laparoscopic resection and operated on between September 21, 2006 and December 31, 2008 at the Department of Surgery, Hospital and J.G. Mendel Oncological Centre Novy Jicin. 6 samples were collected from each patient to determine MRD (system venous blood and bone marrow at the beginning of surgery, venous blood from mesenteric bloodstream, system venous blood after the resection, system venous blood and bone marrow 1 month after the surgery). Detection of MRD on the basis of CEA expression was performed by real-time RT-PCR technique. The results were compared with those obtained within the similar research using the same methodology at the 2(nd) Department of Surgery, University Hospital in Olomouc (the group included 230 patients treated with open resection of CRC). RESULTS: In the group of patients treated with laparoscopic resection, a correlation between positive MRD in the sample of bone marrow collected before the surgery and the stage of the disease was found (p < 0.035). We also recorded the impact of surgical management on MRD occurrence in system venous blood in primary negative patients (p < 0.025). However, in the course of the short period of time we have not found a statistically significant correlation between the finding in patients with stage I-III, and the period prior to the relapse of the disease (p < 0.59). With regard to the results obtained, we can expect a potential direct correlation between a positive MRD finding in system venous blood taken prior to surgery in patients with stage I-III CRC and shorter time of survival (p < 0.075). In the group of patients treated with open resection of CRC, no statistically significant relationship between the stage of the disease and MRD occurrence was found. Incidence of circulating tumour cells (CTC) in the samples of venous blood taken prior to surgery is a prognostically important factor (p < 0.05) from the viewpoint of disease-free survival (DFS). Another prognostically important factor with regard to DFS seems to be the occurrence of disseminated tumour cells (DTC) in the bone marrow taken 1 month after the surgery. CONCLUSIONS: The data recorded suggest a relationship between MRD finding and the disease prognosis. Collection of samples as well as evaluation of results continue as we strive to include more patients in our study and to obtain more data within 5-10 years of the follow-up. The comparison between the data obtained in the laparoscopic approach and the data obtained in open resection performed from the viewpoint of molecular biology did not show a significant difference in MRD detection in the samples collected after the surgery.