Sex and gender perspectives in colorectal cancer.

Historically women were frequently excluded from clinical trials and drug usage to protect unborn babies from potential harm. As a consequence, the impact of sex and gender on both tumour biology and clinical outcomes has been largely underestimated. Although interrelated and often used interchangeably, sex and gender are not equivalent concepts. Sex is a biological attribute that defines species according to their chromosomal makeup and reproductive organ, while gender refers to a chosen sexual identity. Sex dimorphisms are rarely taken into account, in either preclinical or clinical research, with inadequate analysis of differences in outcomes according to sex or gender still widespread, reflecting a gap in our knowledge for a large proportion of the target population. Underestimation of sex-based differences in study design and analyses has invariably led to 'one-drug' treatment regimens for both males and females. For patients with colorectal cancer (CRC), sex also has an impact on the disease incidence, clinicopathological features, therapeutic outcomes, and tolerability to anticancer treatments. Although the global incidence of CRC is higher in male subjects, the proportion of patients presenting right-sided tumours and BRAF mutations is higher among females. Concerning sex-related differences in treatment efficacy and toxicity, drug dosage does not take into account sex-specific differences in pharmacokinetics. Toxicity associated with fluoropyrimidines, targeted therapies, and immunotherapies has been reported to be more extensive for females with CRC than for males, although evidence about differences in efficacy is more controversial. This article aims to provide an overview of the research achieved so far into sex and gender differences in cancer and summarize the growing body of literature illustrating the sex and gender perspective in CRC and their impact in relation to tumour biology and treatment efficacy and toxicity. We propose endorsing research on how biological sex and gender influence CRC as an added value for precision oncology.

Plasmatic BRAF-V600E allele fraction as a prognostic factor in metastatic colorectal cancer treated with BRAF combinatorial treatments.

BACKGROUND: Combination of a BRAF inhibitor (BRAFi) and an anti-epidermal growth factor receptor (EGFR), with or without a MEK inhibitor (MEKi), improves survival in BRAF-V600E-mutant metastatic colorectal cancer (mCRC) over standard chemotherapy. However, responses are heterogeneous and there are no available biomarkers to assess patient prognosis or guide doublet- or triplet-based regimens. In order to better characterize the clinical heterogeneity observed, we assessed the prognostic and predictive role of the plasmatic BRAF allele fraction (AF) for these combinations. PATIENTS AND METHODS: A prospective discovery cohort including 47 BRAF-V600E-mutant patients treated with BRAFi-anti-EGFR ± MEKi in clinical trials and real-world practice was evaluated. Results were validated in an independent multicenter cohort (n= 29). Plasmatic BRAF-V600E AF cut-off at baseline was defined in the discovery cohort with droplet digital PCR (ddPCR). All patients had tissue-confirmed BRAF-V600E mutations. RESULTS: Patients with high AF have major frequency of liver metastases and more metastatic sites. In the discovery cohort, median progression-free survival (PFS) and overall survival (OS) were 4.4 and 10.1 months, respectively. Patients with high BRAF AF (≥2%, n = 23) showed worse PFS [hazard ratio (HR) 2.97, 95% confidence interval (CI) 1.55-5.69; P = 0.001] and worse OS (HR 3.28, 95% CI 1.58-6.81; P = 0.001) than low-BRAF AF patients (<2%, n = 24). In the multivariable analysis, BRAF AF levels maintained independent significance. In the validation cohort, high BRAF AF was associated with worse PFS (HR 3.83, 95% CI 1.60-9.17; P = 0.002) and a trend toward worse OS was observed (HR 1.86, 95% CI 0.80-4.34; P = 0.15). An exploratory analysis of predictive value showed that high-BRAF AF patients (n = 35) benefited more from triplet therapy than low-BRAF AF patients (n = 41; PFS and OS interaction tests, P < 0.01). CONCLUSIONS: Plasmatic BRAF AF determined by ddPCR is a reliable surrogate of tumor burden and aggressiveness in BRAF-V600E-mutant mCRC treated with a BRAFi plus an anti-EGFR with or without a MEKi and identifies patients who may benefit from treatment intensification. Our results warrant further validation of plasmatic BRAF AF to refine clinical stratification and guide treatment strategies.

Analisis estadístico de 134 casos consecutivos de ganglio centinela en el melanoma maligno cutáneo en las islas baleares. Utilidad terapeútica de la biopsia selectiva ganglionar e importancia d ela localización anatómica del tumor primario (2000-2006) / Statistic analyisis of 134 consecutive cases of sentinel lymph node in cutaneous malign melanoma in baleares islands. Therapeutic utility of selective sentinel limph node biopsy biopsy and relevance of anatomic localization of primary tumour (2000-2006)

La biopsia selectiva del ganglio centinela en el melanoma maligno cutáneo nos permite una apropiada estadificación, evitando innecesarias linfadenectomías y verificar que las ideas clásicas de las vías de drenaje linfático no se corresponden con la realidad, existiendo una gran variabilidad según su localización anatómica, y que el Breslow es el factor pronóstico más importante para predecir la supervivencia junto a otros en estos pacientes. La cirugía es pues necesaria para una adecuada clasificación de la enfermedad y planificar su tratamiento, extirpar el tumor primitivo y posibles metástasis de las áreas ganglionares y eliminar metástasis viscerales disminuyendo la masa tumoral para facilitar otros procedimientos. El motivo de este trabajo es observar si existe correlación entre ellos e intentar obtener los resultados que tras una apropiada detección gammagráfica (con un 100% de aciertos en la localización) y quirúrgica del ganglio centinela, determinando si existen diferencias respecto al número de drenajes y de ganglios centinelas extraídos que justifiquen las variaciones encontradas (AU)

The selective biopsy of the sentinel lymph node in the cutaneous malignant melanoma allows us to make an appropriate staging, avoiding unnecessary lymphadenectomies and verify that the classical ideas of lymphatic drainage ways do not correspond with reality, as there is great variability according to anatomic localisation, and the fact that Breslow thickness is the most important prognostic factor for predicting survival along with others in these patients. Thus, surgery is necessary for an adequate classification of the disease and to plan its treatment, remove the primitive tumour and possible metastasis of the ganglionic areas and eliminate visceral metastasis diminishing the tumour mass to facilitate other procedures. The reason for this work is to find out whether there is a correlation between them and try to obtain the results after an appropriate gammagraphic etection (with 100% correct choice in the localisation) and surgery of the sentinel lymph node and determine if there are differences with respect to the number of drainages and extracted sentinel lymph nodes that justify the variations found (AU)

Hidatidosis peritoneal diseminada en curso d eembarazo a término totalmente asintomática. Revisión bibliográfica / Disseminatyed peritoneal hydatidosis asyntomatic in pregnany. A case report and literature review

La asociación de quiste hidatídico y embarazo es rara y ocasiona conductas discutibles sobre la vía del parto. En zonas endémicas la incidencia es de 1/20.000 nacimientos, cuestionándose un progreso rápido de la enfermedad debido a la inmunidad celular reducida en el embarazo; incluso están descritos casos que han llevado a un proceder quirúrgico en el primer trimestre del mismo. Una localización pélvica del quiste puede obstruir el parto vaginal. Apenas hay notificaciones de anafilaxia en pacientes embarazadas con hidatidosis peritoneal, posiblemente porque ya hayan tolerado una diseminación previa. Presentamos un caso de una mujer joven marroquí embarazada y que en los controles ecográficos trimestrales solo evidenció la presencia de un quiste hidatídico con sospecha en las Ecografías ginecológicas en el 7º mes, de diseminación del mismo, lo cual fue puesto de manifiesto en el acto quirúrgico por cesárea sin presentar clínica anterior de anafilaxia. Hacer notar la muy escasa incidencia de esta patología en las Baleares desde 1974 y con un discreto aumento, seguramente ocasionado por la diversa inmigración (AU)

The association between the hydatid cyst and pregnancy is rare and can cause problems during delivery. In endemic zones the incidence is 1 case/ 20.000 deliveries, with a rapid progression of this entity during pregnancy because of a reduced immunity. Some cases that have required surgery during the first three months of pregnancy have been described. A pelvic localization of the cyst can cause an obstruction for the normal vaginal delivery. There are no previous cases of anaphylaxis during pregnancy with peritoneal hydatidosis, maybe because there have been a previous dissemination. We present a case of a young pregnant woman who in the 7th month ecography a hydatid cyst was seen but it was during the caesarean when it could be observed that it was disseminated, without any previous symptoms of anaphylaxia. It must be pointed out that the incidence of this disease in the Balearic Islands is very low but there is an increase in last years mainly because of immigration (AU)

Nuevo tipo de neoválvula en la cirugía dle instestino corto. Estudio experimental en perros previo a su apliaicón clínica / New valve type, in the short bowell surgery. Experimental study in dogs, previous clinic aplication

Un estudio experimental sobre 4 grupos de animales cada uno (perros), nos permitió definir el protocolo quirúrgico y valorar los resultados de una modalidad de restablecer el transito intestinal, tras las práctica en todos ellos, excepto animales controles, de resecciones masivas intestinales que incluyeron el 90% del intestino del delgado, válvula ileocecal, colon derecho, transverso y descendentes mediante 3 tipos de anastomosis: 1) término-terminal yeyuno-sigmoidea; 2) término-terminal yeyuno-sigmoidea según la técnica original de Ricotta y 3) término-terminal yeyuno-sigmoidea con invaginación yeyuno-sigmoidea y cuya realización es de más fácil, cómoda y rápida realización. Al término del trabajo experimental de la tesis y tras su presentación, ya habíamos iniciado (pero no presentado) tras los resultados de la misma, observando que su aplicación experimental y después clínica, fue satisfactoria, siendo técnica fiable, de escasas complicaciones, y no estenosantes y que podíamos aplicarlas en hemicolectomías derechas ampliadas, como en resecciones masivas intestinales, pues su oposición al reflujo cólico por su efecto valvular, contribuirá a evitar la contaminación retrógrada bacteriana (evitando el fallo multiorgánico), y a la regularización mecánica del tránsito intestinal. Su aplicación en un medio séptico seria otra alternativa a la ileostomia cutánea de urgencia (AU)

A new modality for restablishing bowel transit was evaluated in an experimental study with dogs. A surgical procedure wes defined in three groups of dogs (15 in each group). In all animals a masive intestinal resection was made, with a resection of 90% of small bowel including right colon wiht ileocecal valve, middle and left colon, with three modalities of anastomosis: end to small-large bowel, the same with Ricotta technic, and an original technic in which we made a small-large bowel invagination that is quick, convenient and easy. We obtained very good results with experimental and also with clinical appications, with very few complications, and without anastomotical estructures. In right colectomies and in massive intestinal resection, this original technic of anastomosis is very useful for by the reduction of ileocolic reflux and colic contamination by enteric bacteries, and the contribution to regulation of intestinal circulation. Its application in septic conditions can be a good alternative to ileostomy in emergency procedures (AU)

Quiste de inclusión peritoneal multilocular: una extraña lesión pélvica / Multilocular peritoneal inclusion cyst: a rare pelvic lesion

El quiste de inclusión peritoneal multilocular, también llamado mesotelioma quístico benigno, es una rara lesión que afecta al peritoneo abdominal. La etiología es desconocida, pero ocurre predominantemente en mujeres premenopáusicas. Clínicamente, los hallazgos más frecuentes suelen ser dolor abdominal crónico, masa palpable y distensión abdominal, pero también puede ser asintomático o debutar con abdomen agudo. Las pacientes son habitualmente diagnosticadas mediante ultrasonidos, y la cirugía es el tratamiento recomendado primariamente aunque con altas tasas de recurrencias. Presentamos el caso de una mujer de 24 años con dolor abdominal agudo, tratada mediante laparoscopia y exéresis de la lesión (AU)

Neonatal sepsis and meningitis in Mallorca, Spain, 1977-1991.

In a retrospective study at Son Dureta Hospital (Palma de Mallorca, Mallorca, Spain) of the period 1977-1991, 334 cases of culture-proven sepsis and/or meningitis in neonates born at the facility were identified. Overall, there was an incidence rate of 4.9 cases per 1,000 live births. The case-fatality rate was 7.5%. Infection was more frequent in infants of low birth weight, with the exception of infants with meningitis and infections due to group B Streptococcus and Listeria species. The patterns of predominance among bacterial pathogens that were isolated changed during the period studied. From 1977 to 1984, Klebsiella pneumoniae was the most frequent such isolate, but this frequency declined in the following years. Group B Streptococcus organisms and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and late-onset infections, respectively. The frequency with which other pathogens were isolated did not vary significantly during the study period. Invasive infection caused by Candida organisms was found in two patients. The incidence of infection due to group B streptococci has increased in the last few years (to 2.4 cases per 1,000 live births in 1991) and has become a significant problem that requires a thorough epidemiological evaluation.

A 7-year follow-up of newborns vaccinated against hepatitis B.

Of 79 children born to asymptomatic HBsAg chronic carrier mothers and vaccinated at birth against hepatitis B, a total of 71, 66 and 56 could be serologically assessed after 1, 5 and 7 years, respectively. Anti-HBs titres (geometric means) of responders decreased from 2475 to 143 IU l-1 between 1 and 5 years of age and dropped to 82 IU l-1 by 7 years. At this time, a booster dose given to 34 children who showed anti-HBs titres lower or slightly higher than 100 IU l-1 significantly increased titres from 34 to 2985 IU l-1 (p < 0.001). Children whose titres following perinatal vaccination reached 100 to 1000 IU l-1 or above 1000 IU l-1 maintained protective levels (> 10 IU l-1) for 3 and 5 years, respectively. As in adults, anti-HBs titres recorded after the initial vaccination indicate the time at which infants should receive booster vaccination.

Visceral leishmaniasis: another HIV-associated opportunistic infection? Report of eight cases and review of the literature.

Visceral leishmaniasis (VL) is considered an opportunistic infection in immunocompromised patients. We review the clinical, laboratory, and therapeutic data in 63 patients (eight new cases and 55 cases reported in the literature) with Mediterranean VL (kala azar) and HIV-1 infection to determine whether VL should be considered an opportunistic infection in HIV-infected adults. We conclude that: (1) in areas where both leishmaniasis and HIV-1 infection are endemic, VL may be more frequent among HIV-infected adults; (2) in HIV-infected patients, the clinical picture did not differ significantly from classical kala azar, although it often ran a recurrent course, with resistance to antimonial therapy. We propose the inclusion of VL in the IVC-2 subgroup of the Centers for Disease Control (CDC) clinical classification of HIV-1 infection while prospective and larger studies further define whether there are clinical presentations that could justify adding VL to the list of opportunistic infections indicative of AIDS.

Microbiological characteristics of Weeksella virosa (formerly CDC group IIf) isolated from the human genitourinary tract.

Weeksella virosa (formerly CDC group IIf) is a nonsaccharolytic, oxidase- and catalase-positive, gram-negative rod which is unable to grow on MacConkey agar. At 48 h of incubation on blood or chocolate agar, the colonies present a characteristic appearance: intensely mucoid, adherent, and cream colored as a result of the production of a nondiffusible yellow pigment. This microorganism has been isolated predominantly from the female genitourinary tract, which indicates the opportunity for sexual transmission. We present the microbiological study of three strains of W. virosa identified in a study of 707 female genital samples, representing an incidence of 0.42%. At the same time, we analyzed the principal biochemical tests used in the identification of this microorganism and the susceptibilities of the organism to the different antimicrobial agents assayed.

Intradermal and intramuscular route for vaccination against hepatitis B.

A recombinant hepatitis B vaccine was administered to high-risk hospital personnel by intramuscular (20 micrograms) or intradermal (2 micrograms) injections for the primary immunization (n = 69) with three doses and booster immunization (n = 51) with one dose. Basic vaccination performed intramuscularly gave rise to significantly higher seroconversion levels (97.2% versus 78.1%) and geometric mean titres of antibody (1649 versus 126 IUl-1) as compared with the intradermal route. Intradermal administration did not boost antibody titres in patients previously vaccinated intradermally. Adverse reactions were not serious or severe. The intramuscular route is recommended as the procedure of choice when vaccinating against hepatitis B.

Urinary tract infection caused by Enterobacter taylorae.

We present a case of urinary tract infection caused by Enterobacter taylorae in a 70-year-old male with renal lithiasis. The microorganism was isolated in significant numbers from a urine culture. The disappearance of clinical symptoms after antibiotic treatment points to the participation of this microorganism as the etiological agent in the infection.

[Infection caused by the human immunodeficiency virus, hepatitis B virus and delta virus in homosexual males]. / Infección por el virus de la immunodeficiencia humana, el virus de la hepatitis B y el virus delta en varones homosexuales.

Serological markers of hepatitis B (HBV) and human immunodeficiency (HVI) viruses were investigated in the sera of 90 homosexual males. In addition, in HBsAg positive individuals antibodies against delta virus (DV) were also investigated. Forty sera (44.4%) were positive for HBV and HIV, 61 (67.7%) for HBV and 52 (57.7%) for HIV. HBsAg was detected in 8 cases (8.8%), 7 of which had positive anti-HIV sera. In no case infection by DV was detected. These data show the high prevalence of HBV and HIV infection in the study population. They also suggest that the HBsAg carrier status is more common among HIV positive homosexual males and that the investigated homosexual population has not yet been infected by DV.

[Analysis of the prevalence of anti-Campylobacter pylori antibodies detected in a healthy human population]. / Análisis de la prevalencia de anticuerpos anti-Campylobacter pylori detectados en la población humana sana.

A study was made of the prevalence of anti C. pylori in the healthy adult population. The analytical method used was indirect immunofluorescence. An analysis was made of 231 sera (122 males and 109 females) from subjects 20 to 82 years-old. The global positivity detected was 21.1%. There was a slight rise in the percentage of positivities as age increased, reaching the maximum rate in the group over 50 years (2.1%). The titers detected were low and unrelated to age. No significant differences by sex were found in the subjects analyzed.

[Chronic fatigue syndrome associated with Epstein-Barr virus infection]. / Síndrome de fatiga crónica asociado a infección por el virus de Epstein-Barr.

Epstein-Barr virus (EBV) infection is ubiquitous and may result in multiple and widely different clinical features; the most common of these is infectious mononucleosis (IM). Recently, a group of patients has been included in the chronic EBV infection syndrome (EBVIS), with a sustained nonspecific syndrome consisting of asthenia, anorexia, low grade fever and changes in mood, associated with a viral infection not necessarily caused by EBV; this has been called chronic fatigue syndrome (CFS). We report a patient who fulfilled the criteria for CFS associated with EBV after an acute, well documented EBV infection. We discuss its etiological and pathophysiological implications, emphasizing the need for extreme caution in the diagnosis of CFS. A merely clinical diagnosis may hide severe mistakes.