A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients.

SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

Stroke Volume Measurements by Echocardiography and Ultrasonic Cardiac Output Monitor in Children: A Prospective Observational Cohort Study.

OBJECTIVES: Stroke volume (SV) and cardiac output monitoring is a cornerstone of hemodynamic assessment. Noninvasive technologies are increasingly used in children. This study compared SV measurements obtained by transcutaneous Doppler ultrasound techniques (ultrasonic cardiac output monitor [USCOM]), transthoracic echocardiography jugular (TTE-J), and parasternal (TTE-P) views performed by pediatric intensivists (OP-As) with limited training in cardiac sonography (20 previous examinations) and pediatric cardiologists (OP-Bs) with limited training in USCOM (30 previous examinations) in spontaneously ventilating children. METHODS: A single-center study was conducted in 37 children. Each operator obtained 3 sets of USCOM SV measurements within a period of 3 to 5 minutes, followed with TTE measurements from both apical and jugular views. The investigators were blinded to each other's results to prevent visual and auditory bias. RESULTS: Both USCOM and TTE methods were applicable in 89% of patients. The intraobserver variability of USCOM, TTE-J, and TTE-P were less than 10% in both investigators. The SV measurements by OP-As using USCOM, TTE-J, and TTE-P were 46.15 (25.48) mL, 39.45 (20.65) mL, and 33.42 (16.69) mL, respectively. The SV measurements by OP-Bs using USCOM, TTE-J, and TTE-P were 43.99 (25.24) mL, 38.91 (19.98) mL, and 37.58 (19.81) mL, respectively.The percentage error in SV with USCOM relative to TTE-J was 36% in OP-As and 37% in OP-Bs. The percentage error in SV with TTE-P was 33% relative to TTE-J in OP-As and 21% in OP-Bs. CONCLUSIONS: Our findings show that the methods are not interchangeable because SV values by USCOM are higher in comparison with the SV values obtained by TTE. Both methods have low level of intraobserver variability. The SV measurements obtained by TTE-P were significantly lower compared with the TTE-J for the operator with limited training in echocardiography. The TTE-P requires longer practice compared with the TTE-J; therefore, we recommend to prefer TTE-J to TTE-P for inexperienced operators.

Insufficient response to mRNA SARS-CoV-2 vaccine and high incidence of severe COVID-19 in kidney transplant recipients during pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Viral load and duration of BK polyomavirus viraemia determine renal graft fibrosis progression: histologic evaluation of late protocol biopsies.

BACKGROUND: Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis. METHODS: Using a prospective cohort of patients after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months. RESULTS: A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high [71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62-90.0; P = 0.015] or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19-33.7; P = 0.031) with corresponding rise in 'interstitial fibrosis + tubular atrophy' scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years. CONCLUSIONS: These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia.

Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parallel group, open-label, randomized controlled trial.

BACKGROUND: Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. METHODS: From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. RESULTS: Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years. CONCLUSIONS: Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

Tumour necrosis factor-alpha stimulates liver regeneration in porcine model of partial portal vein ligation.

BACKGROUND/AIMS: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Tumor necrosis factor- alpha (TNF-α) is a pleiotropic cytokine that is connected with initial phase of liver regeneration. The aim of this basic pilot study was to accelerate regeneration of liver parenchyma after PVL. The experimental porcine model was developed to be as much compatible as possible with portal vein embolization (PVE) in human medicine. METHODOLOGY: After ligation of portal branches of caudate and right lateral and right medial liver lobes recombinant porcine TNF-α (TNF-α group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed. RESULTS: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05); nevertheless this stimulating effect was lost at the end of experiment. The important differences in biochemical or histological studied parametres between study groups were not proved. CONCLUSIONS: The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-α confirms the role of studied cytokine in priming of liver regeneration.

Risk of Postoperative Bleeding in Tonsillectomy for Peritonsillar Abscess, as Opposed to in Recurrent and Chronic Tonsillitis-A Retrospective Study.

Tonsillectomy is a routine surgery in otorhinolaryngology and the occurrence of postoperative bleeding is not a rare complication. The aim of this retrospective, observational, analytic, cohort study is to compare the incidence of this complication for the most common indications. A group of patients indicated for tonsillectomies for peritonsillar abscess (group I) was compared to a group of patients indicated for chronic and recurrent tonsillitis (group II). There are a lot of pathophysiological differences in patients indicated for acute tonsillectomy for peritonsillar abscess and in patients indicated for elective tonsillectomy for chronic or recurrent tonsillitis. No technique to minimize the risk of bleeding after tonsillectomy has been found and a large part of postoperative bleeding occurs in postoperative home-care, which makes this issue topical. In total, 2842 unilateral tonsillectomies from the years 2014-2019 were included in the study. Bleeding occurred in 10.03% and, surprisingly, despite completely different conditions in the field of surgery (oedema, acute inflammation in peritonsillar abscess), there was no statistically significant difference between incidence of postoperative bleeding in the studied groups (p = 0.9920). The highest incidence of bleeding was found in the patients of group I on the eighth postoperative day, with those aged 20-24 years (p = 0.0235) being the most at risk, and in group II, on the sixth postoperative day, with those aged 25-29 years (p = 0.0128) and 45-49 years (p = 0.0249) being the most at risk.

Outcomes and Prognostic Factors Following Surgical Treatment of Pulmonary Metastases from Colorectal Carcinoma.

BACKGROUND/AIM: The lungs are the second most common site of cancer dissemination. The aim of this study was to analyze a cohort of patients operated for pulmonary metastases from colorectal carcinoma over a period of 18 years. PATIENTS AND METHODS: In a group of 104 patients, relations were sought between overall survival or disease-free survival and preoperative levels of selected biomarkers, number of metastases and the condition of the intrathoracic lymphatic nodes. Median observation period was 63 months. RESULTS: The 5-year survival rate was 54.3%. Risk of disease progression and risk of death increases in case of occurrence of 2 or more metastases, affection of intrathoracic lymph nodes and levels of CA 19-9, TPS or CEA above cut-off value. CONCLUSION: Prognostic factors that determine overall survival as well as disease-free survival are the number of metastases, the condition of intrathoracic lymphatic nodes and the preoperative levels of biomarkers.

A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer.

BACKGROUND: Optimal chemotherapy (CT) for advanced breast treatment should be effective, well tolerated and convenient. In this study the efficacy and safety of the fully oral combination of oral vinorelbine (Navelbine Oral) plus capecitabine (Xeloda) in metastatic breast cancer (MBC) patients pretreated with anthracycline, was evaluated. PATIENTS AND METHODS: In this phase II multicenter study, this combination CT was given as a first- or second-line therapy for MBC. The treatment schedule was: oral vinorelbine 60 mg/m2 day 1 and day 8 plus capecitabine 1,000 mg/m2 twice daily from day 1 to day 14, every 21 days. RESULTS: One hundred and fifteen patients were included in this trial. The median age was 58 years (range: 40-75). All the patients had received prior anthracycline-based chemotherapy. The combination was well tolerated, with, in particular, only 0.8% of patients presenting with febrile neutropenia. In the intention-to-treat (ITT) population, an objective response was achieved in 65 patients (56.5%). A complete response was achieved in 22 patients (19.1%); partial response in 43 patients (37.4%); stable disease in 36 patients (31.3%), and progressive disease was observed in 14 patients (12.2%). After a median follow-up of 10.0 months, the median progression-free survival (PFS) was 10.5 months and the median survival was 17.5 months. CONCLUSION: Oral vinorelbine-capecitabine shows very promising activity and low toxicity in MBC treatment, with high compliance of the patients.

Tumor markers in patients with relapse of colorectal carcinoma.

AIM: To evaluate CEA and CA19-9 in a long-term follow-up after radical surgery for colorectal cancer. PATIENTS AND METHODS: A total of 1,090 patients were operated on for colorectal cancer, 716 patients underwent R0 resection, 631 patients were under further surveillance, relapse was diagnosed in 122 patients (20%), 74 patients were indicated for reoperation The resectability of the relapse was 35%. An AxSYM instrument (Abbott) was used for analysis. RESULTS: At the time of relapse both markers were normal in 31% of the patients. When relapse was diagnosed, in patients with normal preoperative levels, CEA and CA19-9 were below cut-off in 48% and 79%, respectively, and in those with primary elevation, they were again elevated in 78% and 64%, respectively. CONCLUSION: The surveillance based only on CEA and/or CA19-9 was cost-effective, but failed to disclose 1/3 of patients suffering from relapse; these markers must be combined with liver and chest imaging methods and colonoscopy.

Changes of serum thymidine kinase in children with acute leukemia.

BACKGROUND: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation tumor marker. Our main goal was to determine the significance of elevated TK levels as a relapse marker during follow-up with child patients suffering from acute leukemia. PATIENTS AND METHODS: TK serum levels in 38 children with acute leukemia (34 lymphoblastic, 4 myeloblastic) were determined using radio-receptor analysis (RRA, Immunotech, Prague, USA). All patients included in this study had had TK examined before the start of the treatment and at least twice during the follow-up. RESULTS: Our results showed that TK serum levels at the time of diagnosis were extremely high (78-5826 U/l, median value 403 U/l, normal < 8 U/l), while in remission TK serum levels were much lower (5-80 U/l, median value 31 U/l). During relapse of acute leukemia (5 cases), TK levels increased considerably to measurements between 120-800 U/l (median value 324 U/l). The study showed that the elevation of TK serum levels during follow-up was a helpful marker for the recognition of an early stage of relapse and in some cases occurred as early as one month before the appearance of clinical signs. Sensitivity in this case was 87% and thus TK serum levels seem to be a very good parameter during follow-up because of acceptable sensitivity, low cost (4 $/sample) and the elimination of a requirement for screening of bone marrow samples. CONCLUSION: While TK serum levels were helpful in predicting relapse during follow-up, it is necessary to note that they did not correlate with prognosis in our group of patients during the time of the initial diagnosis of acute leukemia.

Recurrence of colorectal liver metastases after surgical treatment: multifactorial study.

BACKGROUND/AIMS: The authors evaluated the significance of various factors regarding the recurrence of colorectal liver metastases (CLM) after liver resection or radiofrequency ablation. METHODOLOGY: 82 patients were operated on for CLM at our department between 1998 and 2003. Radical surgery was performed in 58 patients (74.4%), an palliative surgery in 20 (25.6%). Recurrence of the disease was recorded in 53 patients (71.6%), 21 (28.4%) were without any sign of recurrence. The factors examined in the multifactorial analysis were: age and sex, localization of the primary carcinoma, Dukes classification, grading, histology, microscopically free resection line, chemotherapy and radiotherapy after colorectal or liver surgery, different types of liver resection, radical versus palliative liver surgery, complication after liver surgery, laterality of metastatic process, number of metastases, blood transfusion, staging, repeated liver surgery. Long-rank and Wilcoxon test were used for the statistical evaluation. RESULTS: The factors statistically significant for disease-free interval after liver surgery were: unilaterality of metastatic process, microscopically free resection line, radical versus palliative surgical treatment. The survival rates after liver surgery and after the primary operation were dependent on grading, age, radical versus palliative resection, Dukes classification and staging. CONCLUSIONS: These factors could play an important role as predictors of colorectal cancer recurrence in patients' follow-up period after liver surgery for CLM.

Liver Resections for Colorectal Metastases in Patients Aged Over 75 Years.

BACKGROUND: Concerns regarding postoperative complications following liver resection for colorectal liver metastases (CLMs) in elderly patients may lead to preference for conservative therapy. The aim of this study was to evaluate the role of patient age in the development of postoperative complications. PATIENTS AND METHODS: Surgical complications were evaluated in 712 patients who underwent surgery for CLMs over the past 13 years. Seventy-two patients (10.1%) were aged ≥75 years and 640 (89.9%) <75 years. The significance of the type of liver resection, preoperative American Society of Anesthesiologists classification (ASA), Child-Pugh classification,body mass index, quality of liver tissue and preoperative oncological treatment for the development of postoperative complications were evaluated. RESULTS: We did not find any difference in the incidence of early postoperative complications between the two groups of patients. A preoperative ASA score of 3.4 (p<0.001) was the principal factor for developing postoperative complications in patients aged ≥75 years. Postoperative complications in patients with an ASA score of 3.4 were more frequent when the body mass index was >26 kg/m2 (p<0.02). CONCLUSION: Patient age does not represent a contraindication to liver resection for CLMs. An ASA score of 3 or 4 and a body mass index >26 kg/m2 are risk factors for development of early postoperative complications.

The impact of cytomegalovirus disease and asymptomatic infection on acute renal allograft rejection.

BACKGROUND: Cytomegalovirus (CMV) disease is a risk factor for allograft rejection in renal transplant (RTx) recipients. However, the role of asymptomatic CMV infection remains controversial. OBJECTIVES: To determine the impact of CMV disease and asymptomatic infection on biopsy-proven acute rejection (BPAR) during 12 months post-RTx. STUDY DESIGN: A total of 106 consecutive RTx recipients at risk for CMV (donor and/or recipient CMV seropositive) were followed prospectively for 12 months post-RTx. CMV activity was monitored using nested PCR from whole blood. Three-month prophylaxis with valacyclovir or ganciclovir was given to 94 patients. BPAR episodes were classified according to the Banff 97 criteria. Multivariate Cox proportional hazards model was used to estimate the effect of CMV disease, asymptomatic infection, and other covariates on BPAR. RESULTS: Asymptomatic CMV infection occurred in 23% of the patients and 10% developed CMV disease. The incidence of BPAR was 29%. CMV disease was an independent risk factor for BPAR (HR=3.0, P=0.014), while asymptomatic CMV infection was not (P=0.987). In addition to CMV disease, expanded criteria donor and donor age were independent predictors for BPAR. In univariate analysis, valacyclovir (HR=0.26, P=0.008) decreased the risk of BPAR. A similar trend was observed with ganciclovir (HR=0.42, P=0.058). Only valacyclovir remained significant in multivariate analysis (HR=0.18, P=0.044). CONCLUSIONS: CMV disease, but not asymptomatic infection, is an independent risk factor for BPAR during the first 12 months post-RTx.

Quantitative estimation of CEA and CK20 expression in tumour tissue of colorectal cancer and its liver metastases with reverse transcription and real-time PCR.

BACKGROUND: Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) are established tumour markers and the CEA pre-operative levels in serum have prognostic value. The aim of this study was to verify the usefulness of the estimation of CEA and CK20 gene expressions in tissues of colorectal cancers and their liver metastases. PATIENTS AND METHODS: Two hundred and twenty-two specimens of colorectal cancers, their liver metastases, other liver tumours and control tissues were analysed by reverse transcription combined with real-time PCR. RESULTS: The expressions of CEA and CK20 were significantly higher in tumours than in controls; there were differences between tumour types and no relationship to staging or clinical development was found. CK20 expression was inversely dependent on grading. The CEA expression in tumours did not correlate with the CEA levels in serum, but did correlate with serum tissue-specific polypeptide antigen (TPS). CONCLUSION: The measurement of CEA and CK20 gene expressions in tumours did not supply any new prognostic information, but raised the question of the mechanism releasing CEA into the blood.

Multiorgan resections for advanced colorectal cancer.

BACKGROUND: A retrospective review is presented of a single institution's experience with multivisceral resections for locally-advanced colorectal cancer. MATERIALS AND METHODS: Twenty-eight patients, who had undergone RO multiorgan resection, were identified from the database of a total of 1150 patients operated on for colorectal carcinoma in the years 1995-2005 at a single center. There were twelve total pelvic exenterations and 16 patients had undergone en bloc primary tumor resection with adherent organs, such as the spleen, diaphragm, pancreas, stomach, kidney, etc. The patients were followed-up according to a standard protocol. RESULTS: The post-operative mortality was 7%, the average follow-up 21.6 months and the 5-year survival 45%. CONCLUSION: Our results confirmed that, in the case of invasion of colorectal cancer to the adjacent intra-abdominal organs or structures, multiorgan resection 'offers the only chance of potentially-curative treatment.

Do Weather Phenomena Have Any Influence on the Occurrence of Spontaneous Pneumothorax? / ¿Tienen los fenómenos meteorológicos alguna influencia en la aparición de neumotórax espontáneo?

INTRODUCTION: The objective of this study was to assess the impact of weather phenomena on the occurrence of spontaneous pneumothorax (SP) in the Plzen region (Czech Republic). METHODS: A retrospective analysis of 450 cases of SP in 394 patients between 1991 and 2013. We observed changes in average daily values of atmospheric pressure, air temperature and daily maximum wind gust for each day of that period and their effect on the development of SP. RESULTS: The risk of developing SP is 1.41 times higher (P=.0017) with air pressure changes of more than±6.1hPa. When the absolute value of the air temperature changes by more than±0.9°C, the risk of developing SP is 1.55 times higher (P=.0002). When the wind speed difference over the 5 days prior to onset of SP is less than 13m/sec, then the risk of SP is 2.16 times higher (P=.0004). If the pressure difference is greater than±6.1hPa and the temperature difference is greater than±0.9°C or the wind speed difference during the 5 days prior to onset of SP is less than 10.7m/s, the risk of SP is 2.04 times higher (P≤.0001). CONCLUSION: Changes in atmospheric pressure, air temperature and wind speed are undoubtedly involved in the development of SP, but don't seem to be the only factors causing rupture of blebs or emphysematous bullae.

Contribution of the ß-ureidopropionase (UPB1) gene alterations to the development of fluoropyrimidine-related toxicity.

BACKGROUND: An impairment of the 5-fluorouracil (5-FU) catabolic pathway, represented by alterations in the dihydropyrimidine dehydrogenase (DPYD) gene, is considered a crucial factor contributing to the development of 5-FU-related toxicity. The ß-ureidopropionase (BUP1) enzyme catalyzes the final step in the 5-FU catabolic pathway; however, alterations in the UPB1 gene coding for the BUP1 enzyme have not yet been analyzed in fluoropyrimidine (FP)-treated patients suffering from 5-FU-related toxicity. METHODS: We have performed a mutation analysis of the entire coding sequence of UPB1 based on denaturing high-performance liquid chromatography in 113 cancer patients treated by FP-containing regimes. These patients included 67 individuals suffering from severe 5-FU-related toxicity and 46 individuals with excellent tolerance of chemotherapy. RESULTS: Nine UPB1 variants were detected in the subpopulation of patients with severe toxicity, including a novel mutation affecting the coding sequence (c.872_873+11del13). An analysis of UPB1 variants on 5-FU-related toxicity in the population of all analyzed patients revealed an association between the c.-80C>G (rs2070474) variant and gastrointestinal toxicity. A strong positive correlation was found between the carriers of the c.-80 GG genotype and the development of severe (grade 3-4) mucositis (OR = 7.5; 95% CI = 2.60 - 21.60; p = 0.0002). CONCLUSION: Our results suggest that UPB1 variants may contribute to the development of 5-FU-related toxicity in some FP-treated patients; however, the role of UPB1 alterations is probably less significant than that of DPYD alterations.