Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer.

BACKGROUND: The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS: A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION: Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.

ANTECEDENTES: No se conoce la seguridad y la eficacia oncológica de la re-resección laparoscópica del cáncer incidental de vesícula biliar. Este estudio tiene como objetivo comparar las re-resecciones del cáncer incidental de vesícula biliar por vía laparoscópica y vía abierta, minimizando el sesgo de selección. MÉTODOS: Estudio de cohortes observacional, retrospectivo y multicéntrico de pacientes con cáncer incidental de vesícula biliar que se sometieron a una re-resección con intención curativa en 4 centros entre 2000 y 2017. Se analizó la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurrence free survival, RFS) según intención de tratamiento. Se calculó la probabilidad inversa de la ponderación del tratamiento quirúrgico utilizando puntuación de propensión. RESULTADOS: Se incluyeron 255 pacientes con re-resección (190 por vía abierta y 65 por vía laparoscópica). Se convirtieron 19 pacientes del grupo laparoscópico. El único factor relacionado con la conversión fue la realización de la cirugía antes de año 2011. La mediana de la estancia hospitalaria fue más corta tras la re-resección laparoscópica (4 versus 6 días; P < 0,001). La OS a tres años fue del 87% y del 62% (P = 0,502) para las re-resecciones laparoscópicas y abiertas, respectivamente). Los factores predictivos independientes relacionados con una peor OS fueron el hallazgo de cáncer residual en el momento de la re-resección (cociente de riesgos instantáneos, hazard ratio, HR 1,91; i.c. del 95% 1,17-3,11), una pérdida hemática > 500 ml (HR 1,83; i.c. del 95% 1,23-2,74) y la presencia de ≥ 4 ganglios positivos (HR 3,11; i.c. del 95% 1,46-6,65). En el análisis de riesgo competitivo, la RFS fue mayor para la resección laparoscópica (P = 0,038), pero no hubo diferencias en la OS entre ambos grupos. Los factores predictivos independientes de peor RFS fueron la detección de 1-3 ganglios positivos (HR 2,16; i.c. del 95% 1,29-3,60), ≥ 4 ganglio positivos (HR 4,39; i.c. del 95% 1,96-9,82) y el cáncer residual (HR 2,42; i.c. de 95% 1,46-4,0). CONCLUSIÓN: En pacientes seleccionados, los resultados oncológicos de la re-resección laparoscópica de un cáncer incidental de vesícula biliar no son inferiores a los que se obtienen por vía abierta. Una mayor difusión de las técnicas laparoscópicas avanzadas y una oportuna derivación de los pacientes con cáncer de vesícula biliar incidental a centros especializados podrían permitir que un mayor número de pacientes se beneficiaran de este abordaje.

Is there a role for cervical assessment and uterine artery Doppler in the first trimester of pregnancy as a screening test for spontaneous preterm delivery?

OBJECTIVE: To evaluate the role of cervical length (CL) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks as predictors of spontaneous preterm delivery (sPTD) in a Chilean population. METHODS: This was a prospective study of asymptomatic women with singleton pregnancies attending for a nuchal translucency scan at 11+0 to 13+6 weeks' gestation and who underwent a transvaginal scan for evaluation of CL and UtA-PI. Exclusion criteria were fetal and pregnancy complications (other than sPTD) and iatrogenic delivery at<34 weeks. Measurements of CL and UtA-PI were adjusted for fetal crown-rump length and maternal characteristics and expressed as multiples of the median (MoM) of the unaffected group. Prediction of sPTD using maternal and pregnancy characteristics was studied using logistic regression analysis. RESULTS: A total of 3480 women were recruited into the study and, after application of exclusion criteria, 3310 were included in the analysis. The rate of sPTD at<34 weeks was 0.9% (n=31). A previous PTD had occurred in 7.4% of parous women. Patients with sPTD in the index pregnancy were characterized by a significantly higher prevalence of previous PTD (12.9% vs 3.7%, P<0.05). No significant difference was found in either CL or UtA-PI between pregnancies with and without subsequent sPTD. Logistic regression analysis showed that smoking and previous PTD were significantly associated with sPTD at<34 weeks. The combination of these characteristics provided a detection rate of 26% with a false-positive rate of 8%. CONCLUSIONS: Neither UtA-PI nor CL during the first trimester was shown to be a useful predictor of early sPTD. However, a combined model that includes smoking and previous PTD predicts approximately one-quarter of those women destined to deliver at<34 weeks, with a false-positive rate of 8%.

Role of the glucose tolerance test as a predictor of preeclampsia.

OBJECTIVE: To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women. METHODS: A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves. RESULTS: Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate. CONCLUSIONS: This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women.

Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy.

OBJECTIVE: To develop a predictive model for pre-eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy. METHODS: This was a nested case-control study within a pre-eclampsia screening project that involved 5367 asymptomatic pregnant women undergoing routine transvaginal uterine artery (UtA) Doppler at 11 + 0 to 13 + 6 weeks. Following exclusions, there were 70 pregnant women who later developed pre-eclampsia and 289 control patients enrolled during the first trimester who had serum or plasma samples taken at enrolment available for the purposes of this study. Of these, 17 pregnancies were diagnosed with early-onset (delivery < 34 weeks) pre-eclampsia and 53 with late-onset (delivery ≥ 34 weeks) pre-eclampsia. The lowest, highest and mean of left and right UtA pulsatility indices (PI) were calculated. Blood samples were stored at -84 °C until biochemical analysis for markers of vasculogenesis was performed. The distributions of the lowest UtA-PI and the biochemical markers were adjusted for maternal characteristics, expressed as multiples of the median (MoM), and compared between groups. Logistic regression analysis was used to evaluate if any variable was significantly associated with pre-eclampsia. RESULTS: Pregnancies that later developed pre-eclampsia were associated with higher maternal prepregnancy body mass index. An increased lowest UtA-PI was significantly associated with both early- and late-onset disease. Placental growth factor (PlGF) MoM was significantly reduced in women who later developed early- or late-onset pre-eclampsia compared with controls (median (interquartile range), 0.69 (0.33-1.46) and 1.10 (0.39-1.56), respectively, vs 1.19 (0.65-1.84), P < 0.05). Different combined models were generated by logistic regression analysis, and the detection rate with a fixed 10% false-positive rate was 47% and 29% for early- and late-onset pre-eclampsia, respectively. CONCLUSION: Pregnancies that later developed early or late pre-eclampsia were characterized by impaired placentation and an anti-angiogenic state during the first trimester of pregnancy. Regression models which include maternal characteristics, UtA Doppler and PlGF can apparently predict approximately half of pregnancies that will be complicated by early-onset pre-eclampsia. We believe more research in several areas is needed to aid in the creation of a better and more population-specific screening test for pre-eclampsia during the first trimester of pregnancy.

Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

Liver transplantation results for hepatocellular carcinoma in Chile.

UNLABELLED: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Liver transplantation is the best treatment for HCC; it improves survival, cures cirrhosis, and abolishes local recurrence. We describe the outcomes of patients with HCC who underwent liver transplantation in two liver transplantation centers in Chile. METHODS: This study is a clinical series elaborated from the liver transplantation database of Pontificia Universidad Católica and Clínica Alemana between 1993 and 2009. The survival of patients was calculated using the Kaplan-Meier survival analysis. The significant alpha level was defined as <.05. RESULTS: From 250 liver transplantations performed in this period, 29 were due to HCC. At the end of the study, 25 patients (86%) were alive. The mean recurrence-free survival was 30 months (range 5 months to 8 years). The 5-year survival for patients transplanted for HCC was >80%; however, the 5-year overall survival of patients who exceeded the Milan criteria in the explants was 66%. There was no difference in overall survival between patients transplanted for HCC versus other diagnosis (P = .548). CONCLUSION: This series confirmed that liver transplantation is a good treatment for patients with HCC within the Milan criteria.

Screening for trisomy 21 during the routine second-trimester ultrasound examination in an unselected Chilean population.

OBJECTIVE: To evaluate the performance of a detailed ultrasound examination during the second trimester as a screening test for Down syndrome in an unselected Chilean population. METHODS: This was part of an ongoing longitudinal study. Included were 3071 women with singleton pregnancies who underwent routine ultrasound examination between 21 + 0 and 25 + 6 gestational weeks as a screening test for chromosomal abnormalities and major congenital structural defects, and who were diagnosed as having trisomy 21 or being chromosomally normal. Maternal age, and eight soft markers and cardiac defects associated with Down syndrome were evaluated as a screening test using logistic regression analysis. RESULTS: The incidence of Down syndrome was 0.6%, and the mean maternal age was 29.4 +/- 6.2 years. At least one of four soft markers (absent nasal bone, nuchal edema, short femur, echogenic foci) and/or cardiac defects was present in 77.8% of Down syndrome fetuses and in 3.1% of normal fetuses. Furthermore, with a false-positive rate of 1%, the detection rate using the combined model of ultrasound markers and maternal age was 72.2%. CONCLUSIONS: Second-trimester ultrasound markers are able to detect over 70% of Down syndrome fetuses with only a 1% false-positive rate.

The novel use of Rh(I) complexes with naphthyridine ligands and poly(oxyethylene) as antitumorals.

Rh(I) complexes adsorbed on polymers, as a way to improve their transport and solubility properties, were studied as antitumor agents. The binding constants of the complexes to the polymer were evaluated in order to determine the conditions for maximum association to the vehicle. The toxicity of the pure complexes and those bound were determined in vivo using female mice. [Rh(NBD)(2,4N)]CIO4, complex A; where NBD = norbornadiene, (2,4N) = 3,3'-dimethylene-2,2'-di-1,8-naphthyridine, was investigated on primary solid tumors and ascitic tumors. [Rh(NBD)(3,4N)]CIO4, complex B; where (3,4N) = 3,3'-trimethylene-2,2'-di-1,8-naphthyridine, was investigated on ascitic tumors. These Rh(I) complexes appear to be promising drugs because of their solubility in aqueous polymer, which make them easier to handle in comparison with the neutral species. These complexes show a similarity to cisplatin by reducing tumor growth and by increasing the survival life span of mice. Poly (oxyethylene) was used to solubilize these poorly water-soluble compounds and to stabilize the compounds in the solution before injection. These studies suggest that both complexes, A and B, are good candidates for tumor control growth and increase the survival time.