Thyroidectomy via unilateral axillo-breast approach (UABA) with gas insufflation: prospective multicentre European study.

BACKGROUND: Extracervical approaches for thyroidectomy are seldom explored in the western population. The objective of this study was to evaluate the outcomes of hemithyroidectomy via endoscopic unilateral axillo-breast approach (UABA) with gas insufflation. METHOD: Consecutive patients undergoing UABA hemithyroidectomy for symptomatic benign or cytologically indeterminate nodules (Bethesda III lesions) of less than 5 cm from July 2015 to December 2020 at three European institutions were included. Patients were excluded if presenting with a BMI more than 25 kg/m2, had previous neck surgery and/or radiation, had bilateral thyroid lesions, retrosternal goitre, Hashimoto thyroiditis or Graves' disease. Follow-up was carried out at 2 weeks, 3 months and 1 year. Outcomes of interest were surgical (including operating time, mean duration of hospital stay and complications) and self-assessed cosmetic outcomes. RESULTS: Out of 984 patients treated with hemithyroidectomy during the study interval, 253 were selected, including 214 women and 39 men. Patients' mean age was of 46.6 years with a mean BMI of 22.57. Mean operating time was 72.9 minutes. A transient recurrent laryngeal nerve injury was reported in 3.6 per cent of the patients, but none was persistent. Transient pectoral/cervical hypoesthesia was noted in 24.1 per cent of patients, with no permanent hypoesthesia. Skin burns and subcutaneous hematoma developed in 2.4 per cent and 2 per cent of patients but resolved within the third month after surgery. There was no tracheal/oesophageal perforation, conversion to open surgery or reoperation. The final pathology revealed 241 benign nodules, nine underlying papillary thyroid carcinomas, and three cases of follicular carcinoma. Hospital discharge was achieved on the first in 68.8 per cent of the patients and on the second postoperative day in 31.2 per cent of the cases. All patients were satisfied with the cosmetic aspect. CONCLUSION: In selected patients, UABA with gas insufflation for hemithyroidectomy could be performed for the treatment of unilateral thyroid pathologies.

CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer.

CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability.

Inhibitory effects of leptin on pancreatic alpha-cell function.

OBJECTIVE: Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in alpha-cell function has not been studied in detail. In the present study, we have investigated this functional interaction. RESEARCH DESIGN AND METHODS: The presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp and Ca(2+) signals by confocal microscopy. Exocytosis and glucagon secretion were assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS: The expression of several ObR isoforms (a-e) was detected in glucagon-secreting alphaTC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in alphaTC1-9 cells as well as in mouse and human alpha-cells. The application of leptin (6.25 nmol/l) hyperpolarized the alpha-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l glucose. Additionally, leptin inhibited Ca(2+) signaling in alphaTC1-9 cells and in mouse and human alpha-cells within intact islets. A similar result occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and were counteracted by the phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement of this pathway in leptin action. CONCLUSIONS: These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipoinsular communication.

[Prediction of prognosis of patients with pancreatic adenocarcinoma with curative intent resection by means of histologic grade and pathologic N stage]. / Predicción del pronóstico de los pacientes con adenocarcinoma pancreático resecado con intención curativa mediante el grado histológico y el estadio N patológico.

BACKGROUND AND OBJECTIVE: Pancreatic cancer has the poorest prognosis of any common gastrointestinal malignancy, with a 5-year overall survival of less than 5%. A better knowledge of prognostic factors related to this neoplasia might help improve the survival of these patients. We evaluated the prognostic significance of different factors in both overall survival and tumor recurrence in patients with pancreatic adenocarcinoma who had undergone pancreatic resection with curative intent. PATIENTS AND METHOD: All patients with pancreatic adenocarcinoma submitted to surgical resection in our unit from January 1995 to February 2005 were evaluated. Twenty-three pre-surgical, therapeutic, and histopathologic variables were analyzed. Univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) analyses were performed to select independent prognostic factors. RESULTS: Ninety-four patients were evaluated. The median age of patients was 63 years and 53% were woman. The probability of overall survival was 63% at 1 year, 18% at 3 years, and 8% at 5 years, with a median survival of 18 months. Univariate analysis identified performance of adjuvant therapy, histologic grade, percentage of involved-resected lymph nodes, pathologic N stage, and pathologic TNM stage as variables associated with overall survival. On the other hand, the probability of tumor recurrence was 52% at 1 year, 83% at 3 years, and 91% at 5 years, with a median time to tumor recurrence of 12 months. Predictive variables of tumor recurrence in the univariate analysis were preoperative N stage, preoperative TNM stage, postoperative CA 19.9 serum concentration, histological grade, percentage of involved-resected lymph nodes, pathologic N stage and pathologic TNM stage. Multivariate analysis identified histological grade and pathologic N stage as independent predictive factors of both overall survival (histologic grade: HR=2.341 [CI 95%, 1.342-4.098; p=0.003]; pathologic N stage: HR=2.242 [1.213-4.149; p=0.01]) and tumor recurrence (histological grade: HR=1.742 [CI 95%, 1.121-3.086; p=0.05]; pathologic N stage: HR=2.096 [1.089-4.032; p=0.027]). CONCLUSIONS: The histological grade and pathologic N stage predict the prognosis of patients with pancreatic adenocarcinoma after surgical resection.

Predicción del pronóstico de los pacientes con adenocarcinoma pancreático resecado con intención curativa mediante el grado histológico y el estadio N patológico / Prediction of prognosis of patients with pancreatic adenocarcinoma with curative intent resection by means of histologic grade and pathologic N stage

Fundamento y objetivo: el cáncer de páncreas tiene el peor pronóstico de los tumores gastrointestinales, con una supervivencia media a los 5 años de menos del 5%. Un mejor conocimiento de los factores pronósticos de esta neoplasia podría ayudarnos a mejorar la supervivencia de estos pacientes. El objetivo de este estudio fue evaluar el significado pronóstico de diferentes factores en relación tanto con la supervivencia general como con la recurrencia tumoral en pacientes con adenocarcinoma pancreático intervenidos con intención curativa. Pacientes y método: se ha evaluado a todos los pacientes con adenocarcinoma pancreático intervenidos en nuestra unidad desde enero de 1995 a febrero de 2005. Se analizaron 23 variables prequirúrgicas, terapéuticas e histopatológicas. Para seleccionar los factores pronósticos independientes se realizó un análisis univariable (con curvas de Kaplan-Meier y prueba de rangos logarítmicos) y otro multivariable (regresión de Cox). Resultados: se evaluó a 94 pacientes. La mediana de edad de los pacientes fue 63 años y el 53% eran mujeres. La supervivencia general fue del 63% al año, del 18% a los 3 años y del 8% a los 5 años, con una mediana de supervivencia de 18 meses. El análisis univariable identificó como variables relacionadas con la supervivencia general el grado histológico, el porcentaje de ganglios afectados de los que fueron resecados, el estadio N patológico y el estadio TNM patológico. Por otro lado, la probabilidad de recurrencia tumoral fue del 52% al año, del 83% a los 3 años y del 91% a los 5 años, con una mediana para la recurrencia tumoral de 12 meses. Las variables predictivas de recurrencia tumoral en el análisis univariable fueron el estadio N preoperatorio, el estadio TNM preoperatorio, la concentración sérica postoperatoria de CA19.9, el grado histológico, el porcentaje de ganglios afectos de los que fueron resecados, el estadio N patológico y el estadio TNM patológico. El análisis multivariable identificó el grado histológico y el estadio N patológico como los factores predictivos independientes tanto de la supervivencia general (grado histológico: hazard ratio [HR]=2,341; intervalo de confianza[IC] del 95%, 1,342¿4,098; p=0,003; estadio N patológico: HR=2,242; IC del 95%, 1,213¿4,149; p=0,01) como de la recurrencia tumoral (grado histológico: HR=1,742; IC del 95%, 1,021¿3,086; p=0,05; estadio N patológico: HR=2,096; IC del 95%, 1,089¿4,032; p=0,027). Conclusiones: el grado histológico y el estadio N patológico predicen el pronóstico de los pacientes con adenocarcinoma pancreático después de la resección quirúrgica (AU)

Background and objective: Pancreatic cancer has the poorest prognosis of any common gastrointestinal malignancy, with a 5-year overall survival of less than 5%. A better knowledge of prognostic factors related to this neoplasia might help improve the survival of these patients. We evaluated the prognostic significance of different factors in both overall survival and tumor recurrence in patients with pancreatic adenocarcinoma who had undergone pancreatic resection with curative intent. Patients and method: All patients with pancreatic adenocarcinoma submitted to surgical resection in our unit from January 1995 to February 2005 were evaluated. Twenty-three pre-surgical, therapeutic, and histopathologic variables were analyzed. Univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) analyses were performed to select independent prognostic factors. Results: Ninety-four patients were evaluated. The median age of patients was 63 years and 53% were woman. The probability of overall survival was 63% at 1 year, 18% at 3 years, and 8% at 5 years, with a median survival of 18 months. Univariate analysis identified performance of adjuvant therapy, histologic grade, percentage of involved-resected lymph nodes, pathologic N stage, and pathologic TNM stage as variables associated with overall survival. On the other hand, the probability of tumor recurrence was 52% at 1 year, 83% at 3 years, and 91% at 5 years, with a median time to tumor recurrence of 12 months. Predictive variables of tumor recurrence in the univariate analysis were preoperative N stage, preoperative TNM stage, postoperative CA 19.9 serum concentration, histological grade, percentage of involved-resected lymph nodes, pathologic N stage and pathologic TNM stage. Multivariate analysis identified histological grade and pathologic N stage as independent predictive factors of both overall survival (histologic grade: HR=2.341 [CI 95%, 1.342¿4.098; p=0.003]; pathologic N stage: HR=2.242 [1.213¿4.149; p=0.01]) and tumor recurrence (histological grade: HR=1.742 [CI 95%, 1.121¿3.086; p=0.05]; pathologic N stage: HR=2.096 [1.089¿4.032; p=0.027]). Conclusions: The histological grade and pathologic N stage predict the prognosis of patients with pancreatic adenocarcinoma after surgical resection (AU)

The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation.

We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs. Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)). Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it. The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.

Posttraumatic intrapancreatic aortosplenic fistula causing portal hypertension.

Arterioportal fistulas are uncommon. The case of a patient with massive uncontrollable esophageal variceal bleeding is presented. Reversible portal hypertension was caused by a posttraumatic giant intrapancreatic aortosplenic fistula. Percutaneous closure was unsuccessful, and pancreatectomy was performed to control the bleeding. The case is discussed and the literature on this exceptional cause of portal hypertension is reviewed.

Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors.

BACKGROUND: This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia. METHOD: Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed. RESULTS: SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%). CONCLUSION: SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.