Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands.

BACKGROUND: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited. OBJECTIVE: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice. METHODS AND MATERIALS: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status. RESULTS: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage. CONCLUSION: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Improved outcome by identification of high-risk nonocclusive mesenteric ischemia, aggressive reexploration, and delayed anastomosis.

BACKGROUND: The factors associated with outcome of patients with nonocclusive mesenteric ischemia are poorly defined. METHODS: Over a 7-year period, 34 consecutive patients with nonocclusive mesenteric ischemia were identified. RESULTS: The mean age of the study patients was 63 years (range 31 to 94); 21 of 34 (62%) were men. The mean delay in diagnosis was 31 hours (range 7 hours to 6 days). Seven of 34 (21%) underwent preoperative visceral arteriography. Two of these 7 required surgery, and both died as a result of intestinal infarction. The remaining 27 had the diagnosis made at celiotomy. Among the 29 who were explored, 16 of 29 (55%) had intestinal infarction. Twenty-one of 29 (72%) had segmental bowel injury whereas 8 of 29 (28%) had massive injury. Among those with segmental infarction, primary anastomosis was performed in 12 of 21 patients (57%); 5 of the 12 (42%) died. Nine of 21 patients (43%) underwent delayed anastomosis; 2 of the 9 (22%) died. No patient with massive injury underwent primary anastomosis. Second-look laparotomy was performed on 22 of 29 (76%). Eleven of those 22 (50%) had a further bowel resection. Overall, 16 of 29 (55%) who underwent surgery for nonocclusive mesenteric ischemia are alive. CONCLUSIONS: Improved survival from nonocclusive mesenteric ischemia is dependent upon the identification of high-risk groups, aggressive reexploration, and delayed intestinal anastomosis.

The role of intrarectal ultrasound (IRUS) in staging of rectal cancer and detection of extrarectal pathology.

Intrarectal Ultrasound (IRUS) is rapidly becoming an effective tool in the staging of rectal cancer. Twenty-nine consecutive patients with adenocarcinoma of the rectum underwent both CT scanning and IRUS in the preoperative assessment of rectal cancer in an effort to correlate IRUS staging with surgical pathology, correlate tumor staging comparing IRUS with CT scan, and determine incidence of extrarectal pathology by IRUS. Patients were reviewed as to IRUS stage, results of CT scan, TNM stage of extirpated tumor, incidence of genitourinary pathology, and sonographic result of preoperative radiotherapy (RT). The mean age of all patients was 69 years; there were 25 males and four females. Twenty-four patients underwent proctectomy with either low pelvic anastomosis or end stoma; five underwent local surgical therapy. Thirteen patients received preoperative RT. CT scan correlated poorly with IRUS staging of tumors penetrating the muscularis propria. IRUS overstaged 40 per cent, understaged 5 per cent, and correctly staged 55 per cent of patients when compared with pathological specimens. Eleven of the 25 males (44 per cent) had abnormal prostates by IRUS. Five (20%) had further urologic intervention, resulting in two prostatic cancers found. Our data suggests that CT scan staging correlated poorly with IRUS staging. CT poorly determines depth of rectal tumor wall invasion. IRUS correlated well with pathology and understaged 5 per cent of patients before surgery. Genitourinary abnormalities were detected in a significant number of patients. IRUS is an effective modality for preoperative staging of rectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Levels of tumor necrosis factor alpha/cachectin (TNF alpha) in sera from patients with sickle cell disease.

Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in a group of adult patients with sickle cell disease (SCD), which include 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNF alpha in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml. The percentage of sera with detectable levels of TNF alpha was significantly increased in SCD patients as compared with the normal controls. Mean TNF alpha values in individuals with detectable levels of the cytokine were also significantly higher in the whole group of SCD patients and in patients bearing either SS or SC hemoglobinopathies than in the control group. An inverse correlation was observed between the percentages of Hb F and the levels of TNF alpha found in the sera from the patients.

The effect of volume and number on fragmentation of gallstones by lithotripsy.

Several factors may affect the fragmentation of gallstones by lithotripsy. We hypothesized that stone volume is an important determinant of degree of fragmentation, while number of stones is less important. The volume of 30 single stones was measured in vitro by water immersion. Thirty sets of multiple stones were matched with single stones of similar volumes. The stones were subjected to 750 shock waves (18 kV) with the Dornier MPL 9000 lithotripter. Degree of fragmentation was assessed by passing fragments through sieves of 1, 2, and 4 mm and recording percentage of stone weight which passed through each sieve. The mean percentage of stone weight passing through sieves of 1, 2, and 4 mm for single stones was 38.2, 49.4, and 59.8. The corresponding values for multiple stones were 46.4, 61.3, and 75.4. These values were not significantly different at P less than or equal to 0.05. Thus, there was no significant difference in fragmentation between single and multiple stones when their volumes were similar. The mean volume of stones with 100% of fragments less than 4 mm (0.80 +/- 0.05 cc) was significantly less than that of stones with fragments greater than 4 mm (1.95 +/- 0.14 cc) (P less than 0.0001). There was a significant inverse linear correlation between stone volume and degree of fragmentation (r = -0.65). We conclude that stone volume is an important determinant of degree of fragmentation and may be the most important criterion in selecting patients for lithotripsy. In this in vitro setting, stone number alone had no effect on degree of stone fragmentation.

In vitro antibody synthesis by peripheral blood mononuclear cells from patients with sickle cell disease.

To study the capacity of peripheral blood mononuclear cells (PBMC) from patients with sickle cell disease to synthesize antibodies in vitro, the levels of IgM, IgG, and IgA were quantitated in supernatants of cultured PBMC from a group of asymptomatic adults with sickle cell disease and from normal controls. The rates of spontaneous synthesis of IgM were similar in nonstimulated cultures of PBMC from patients and controls, whereas the amounts of IgG and IgA produced spontaneously by nonstimulated lymphocytes from the patients were significantly greater than those from controls. Similar levels of IgM, IgG, and IgA were detected in the supernatants of cultures stimulated with pokeweed mitogen from patients and controls. Thus, the capacity of PBMC to respond in vitro to pokeweed mitogen was preserved in the patients. The enhanced spontaneous synthesis of IgG and IgA suggests the presence of chronic polyclonal activation of B cells and/or defective regulation of the production of antibodies.

[Hemoglobin variants and hematologic and serologic parameters of the population of El Limón (Aragua State, Venezuela)]. / Variantes hemoglobínicas y parámetros hematológicos y serológicos de población de El Limón (Estado Aragua, Venezuela).

Nine hundred and fifty seven individuals from El Limon (Aragua State, Venezuela) were studied, in order to get information on their hematologic, immunologic and biochemical characteristics. The majority of surnames were of Spanish origin although there were also from other European nationalities. No surname from Venezuelan Indians was found. The pathologic hemoglobin variants (Hb S, Hb C and Hb D-Punjab) have a frequency of 4.3%. Eight albumin variants were detected. The hematologic values suggest a high frequency of iron deficiency. Positivity for hepatitis virus B was found in 0.9% of the population. The carriers and patients for hemoglobin variants per generation was calculated for the whole municipality (5062 and 26, respectively). The African component of the population was estimated in around 18%.

Hemoglobin Hofu associated with beta 0-thalassemia.

A mild anemia (hemoglobin 9 g/dl) was found in a patient from Seville (Spain) with marked morphological abnormalities in the peripheral blood smear. The red cell osmotic fragility showed a mild resistance curve with a mean cell fragility (MCF) of 0.375% NaCl (normal = 0.450). Chemical Chemical and thermal instability test and search for inclusion bodies gave positive results. Hemoglobin electrophoresis at pH 8.9 revealed absence of Hb A, a major component of fast mobility (94%), and increased Hb F and Hb A2 levels (1.5% and 4.6%, respectively). The fast fraction, isolated and purified by means of cellulose acetate electrophoresis, precipitated in acid acetone and treated with urea 8 M and mercaptoethanol, revealed an anomalous beta chain. Trypsin-digested globin peptides were separated by high-voltage electrophoresis at pH 6.4 and ascendant chromatography. With differential staining, an extra peptide was detected in an unusual site, more anodic than alpha Tp4 but in lower position. Peptide map of the fast beta chain, stained with ninhydrin, and also for Tyr, confirmed the position of the new peptide and the absence of the usual beta Tp13. The new peptide, separated by high-voltage electrophoresis at pH 3.5, revealed absence of Val and the presence of an additional Glu residue, which should appear only in position beta 126. The diagnosis of Hb Hofu (alpha 2 beta 2 126 Val----Glu; H4) was reached, thus interpreting its increase and the absence of Hb A, as an association with beta o-thalassemia, producing a mild hemolytic anemia. Evidence was obtained that Hb Hofu is a mild unstable hemoglobin variant.

Caracteristicas hematologicas de la poblacion del Estado Falcon (Venezuela). I. Variantes hemoglobinicas, antigeno Australia y niveles de immunoglobulinas. / Hematologic characteristics of the population of the Falcon State (Venezuela). I. Hemoglobin variants, Australian antigen and immunoglobulin levels

Se estudio 501 donantes voluntarios del Banco de Sangre del Hospital Alfredo van Grieken de Coro en cuanto a variantes o alteraciones hemoglobinicas, antigeno Australia y niveles de inmunoglobulinas. Los grupos sanguineos ABO y Rh mostraron una distribucion que puede considerarse caracteristica para la poblacion venezolana. Se encontro 2,40% con valores aumentados de Hb F, 2,99% con valores moderadamente aumentados de HbA2, 0,40% con valores francamente aumentados de A2, 3,79 de Hb AS, 0,80% de Hb AC y 0,20% de Hb AD Punjab, lo cual indica que en el estado Falcon de cada 11 sujetos 1 tiene alguna variante o alteracion hemoglobinica. Estos resultados representan la intensa mezcla racial que viene operandose en el estado desde la epoca del descubrimiento, habiendose encontrado variantes hemoglobinicas prevalentes en africanos y espanoles. El antigeno Australia, estudiado en 300 donantes, mostro una positividad del 2,33%, que es mayor que la encontrada en Caracas.Los niveles de inmunoglobulinas A, G y M, determinadas en 25 donantes, resultaron un poco mas altos que los obtenidos en donantes de Caracas

Chediak-Higashi syndrome: description of a cluster in a Venezuelan-Andean isolated region.

Fourteen cases of the Chediak-Higashi syndrome found in twelve non-related families living in a defined geographical area not larger than 200 km2 of the Tachira State, Venezuela (population of around 72,000 inhabitants) were diagnosed between 1967 and 1974. The patients were pre-school or nursing age children except one eleven year old female. Six of the patients were male. All showed the same typical somatic characteristics of this syndrome. Four cases were 2 pairs of brothers. Consanguinity of the parents was seen in only two families, even though the majority of them come from the same restricted geographic zone (Pregonero). Since this anomaly is supposedly produced by a rare recessive autosomal gene, the existence of its high frequency in a small Venezuelan region may be explained through the "founder effect" in a population with a high inbreeding coefficient.

Foetal and neonatal albumins in bovines: some biochemical and immunochemical properties.

A study is presented of bovine foetal albumin, a serum protein present in newborns less than 15 days old. As a result of the biochemical and immunochemical analyses, and of the comparison carried out with human foetal albumin, it was concluded that: 1) They share certain characteristics, such as molecular weight, behaviour in the presence of reducing agents, and a great affinity for staining agents. 2) Bovine foetal albumin has a slower electrophoretic mobility than that of the corresponding adult albumin, this aspect differentiating it from human foetal albumin which is faster than human adult albumin.