Treatment strategies for rectal cancer with synchronous liver metastases: surgical and oncological outcomes with propensity-score analysis.

BACKGROUND: The optimal sequence of surgery for rectal cancer (RC) with synchronous liver metastases (SLM) is controversial. OBJECTIVES: The primary objective was to explore differences between the rectum first (RF) and the liver first strategy (LF) to achieve the complete resection (CR) of both tumors. METHODS: Patients diagnosed of RC with resectable or potentially resectable SLM were included. Data collected prospectively were analyzed with an intention-to-treat perspective, adjusting for between-sample differences (propensity score). The complete resection rate (CRR) was the main outcome variable. RESULTS: During a 5-year period, 23 patients underwent the LF strategy and 24 patients the RF strategy. Median overall survival (OS) was 32 months in the LF group and 41 months in the RF group (p = 0.499), and was 51 and 17 months, respectively, for patients achieving or not achieving CR of both tumors (p < 0.001). CRR's were 65% in liver first group and 63% in rectum first group, (p = 0.846). No between-strategy differences in morbidity or duration of treatment were observed. CONCLUSIONS: This study supports the notion that the achievement of CR of RC and SLM should be the goal of oncological treatment. Both RF and LF strategies are feasible and safe, but no between-strategy differences have been found in the CRR.

Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes.

BACKGROUND: The goal of treatment for patients with synchronous liver metastases (SLM) from rectal cancer is to achieve a complete resection of both tumor locations. For patients with symptomatic locally advanced rectal cancer with resectable SLM at diagnosis, our usual strategy has been the rectum first approach (RF). However, since 2014, we advocate for the interval approach (IS) that involves the administration of chemo-radiotherapy followed by the resection of the SLM in the interval of time between rectal cancer radiation and rectal surgery. METHODS: From 2010 to 2016, 16 patients were treated according to this new strategy and 19 were treated according RF strategy. Data were collected prospectively and analyzed with an intention-to-treat perspective. Complete resection rate, duration of the treatment and morbi-mortality were the main outcomes. RESULTS: The complete resection rate in the IS was higher (100%, n = 16) compared to the RF (74%, n = 14, p = 0.049) and the duration of the strategy was shorter (6 vs. 9 months, respectively, p = 0.006). The incidence of severe complications after liver surgery was 14% (n = 2) in the RF and 0% in the IS (p = 1.000), and after rectal surgery was 24% (n = 4) and 12% (n = 2), respectively (p = 1.000). CONCLUSION: The IS is a feasible and safe strategy that procures higher level of complete resection rate in a shorter period of time compared to RF strategy.

Extreme liver surgery as treatment of liver tumors involving the hepatocaval confluence.

OBJECTIVE: Analyze the characteristics, surgical technique, morbidity and survival of patients treated with extreme liver surgery. MATERIALS AND METHODS: We present a series of consecutive patients with malignant liver tumors in hepatocaval confluence treated in a single center with extreme liver surgery (April 2008-March 2015). Data were collected prospectively and analyzed with SPSS 21.0. RESULTS: 12 patients were included. 50 % were male and 50 % were female with a mean age of 59 ± 10 years old. The median of comorbidities was 7 according to the Charlson Age Comorbidity Index. The 75 % of the tumors were metastases, most of them from colorectal cancer. Most of the patients received neoadjuvant chemotherapy and in 58 % preoperative portal embolization was performed. Major hepatectomies were performed (66.7 % extended right hepatectomy, 33.3 % left extended hepatectomy). The 83.3 % of the patients needed vascular reconstruction. Postoperative morbidity was more than grade II in 50 % of the patients according to Dindo-Clavien classification. There was no intraoperative mortality. The postoperative mortality rate at 90 days was 33 % due to hepatic failure and biliary fistula. In December 2015, 33 % of the patients are still alive with a mean survival of 19 months (13-23) with an ECOG Performance Status of 0. CONCLUSION: Extreme liver surgery carries a high rate of morbidity and mortality that seem to increase with age and with higher tumor volumes, according to the literature. It is a therapeutic option to consider in patients with low comorbidity suffering from malignant neoplasms that involve the hepatocaval confluence, when no other treatment with curative intention can be performed.

Retrospective analysis of pathological response in colorectal cancer liver metastases following treatment with bevacizumab.

AIMS: Pathological response has been shown to be a predictor for survival after preoperative chemotherapy and surgical resection of colorectal cancer liver metastases. This retrospective analysis evaluated the effect on pathological response of adding bevacizumab to standard neoadjuvant chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver metastases. METHODS: Patient records from two Spanish centres were retrospectively examined for this analysis. Patients were included if they had stage IV mCRC with liver metastases, were unresectable or marginally resectable tumour before chemotherapy, and had oxaliplatin- or irinotecan-based chemotherapy, with or without bevacizumab, before resection. Tumour response was evaluated using response evaluation criteria in solid tumours (RECIST). Pathological response was assessed by pathologists blinded to treatment. RESULTS: Ninety-five patients were included. Good pathological responses (PR0/PR1) were observed in 37 patients (39 %). The RECIST response rate was 51 %. Only 42 % of patients with a good pathological response had a complete or partial response according to RECIST, while 57 % of those with a poor pathological response had a complete or partial response according to RECIST. RECIST response rates were similar with and without bevacizumab, although 49 % of bevacizumab-treated patients had a good pathological response versus 27 % of those receiving chemotherapy alone (χ (2) P = 0.0302). CONCLUSION: Pathological response may be a better indicator of treatment efficacy than RECIST for patients with mCRC receiving bevacizumab in the neoadjuvant setting. Adding bevacizumab to chemotherapy has the potential to increase pathological response rates. Well-designed prospective clinical studies are required to establish the efficacy and tolerability of this approach.

Preoperative treatment with bevacizumab in combination with chemotherapy in patients with unresectable metastatic colorectal carcinoma.

PURPOSE: This prospective observational study assessed the efficacy of bevacizumab in combination with chemotherapy as preoperative treatment to downsize tumours for radical resection in patients with unresectable metastatic colorectal cancer (mCRC). PATIENTS/METHODS: Patients with mCRC initially unresectable according to predefined criteria were included. Preoperative treatment consisted of bevacizumab (5 mg/kg) combined with oxaliplatin- or irinotecan-based chemotherapy, which was followed by surgery in patients showing clinical benefit. Resection rate was the primary endpoint. Response rate (RR) and clinical benefit of preoperative chemotherapy, and overall survival (OS) were secondary endpoints. RESULTS: A total of 120 eligible patients were included and received preoperative treatment. Chemotherapy was irinotecan-based in 73 (61 %) patients, oxaliplatin-based in 25 (21 %) and 22 (18 %) patients received more than one line. A RR of 30 % and a clinical benefit rate of 73 % were observed with preoperative chemotherapy. Metastatic resection was possible in 61 (51 %) patients. Median OS was 33 months (95 % CI 31-NA months) for patients undergoing surgery, and 15 months (95 % CI 11-25 months) in non-operated patients. Thirty-five patients experienced 59 postoperative complications (morbidity rate 57 %). CONCLUSION: Preoperative bevacizumab-based chemotherapy offers a high surgical rescue rate in patients with initially unresectable mCRC.

Multidisciplinary approach of colorectal liver metastases.

Colorectal cancer (CRC) is the second most common cause of cancer death in Spain. Fifty percent of patients will develop colorectal liver metastases (CLM) during the course of the disease. Less than 20% of patients with CLM are initially resectable and for them 5-year disease-free survival (DFS) is about 20-25%, with a high recurrence rate. CLM is a heterogeneous disease. From a clinical point of view, four main groups can be differentiated: initially resectable, not optimally resectable, unresectable that could be resectable and unresectable that never will be likely to be resected. Treatment of CLM must be established, always, in a multidisciplinary team discussion with an analysis of prognostic factors and resectability. For patients with resectable CLM, the EORTC trial 364 demonstrated that chemotherapy plus surgery is better than surgery alone. Consequently most patients should be treated with perioperative chemotherapy based on oxaliplatin, and if resection has been done without chemotherapy, they should receive adjuvant chemotherapy after R0 resection. Based on oncological factors, the 5-year survival rate after resection of CLM ranges from 60% to only 14% with a poor score. If a patient has more than one of the poor prognostic factors he should probably be referred for preoperative (induction) chemotherapy. Only a minority of patients with CLM are amenable to surgery; therefore, efforts have been made to increase the percentage of patients who could be candidates for resection. Studies, mostly retrospective, have confirmed the ability of neoadjuvant chemotherapy (conversion chemotherapy) to render some metastases resectable. The regimens we must use depend on the KRAS mutational status and the toxicity profiles of drugs in the context of each patient. In k-ras mutated tumours we can use bevacizumab combined with standard chemotherapy or concomitant administration of the three active agents (FOLFOXIRI) in suitable patients. In k-ras wild-type patients, the combination of cetuximab and FOLFIRI-FOLFOX improved response rates and resection rate in phase III-II trials. With a lower level of evidence, panitumumab is an alternative combined with FOLFOX. Bevacizumab is also an alternative as it does not depend on KRAS status. Radiotherapy is becoming an alternative in selected patients, where surgery is not an alternative. For the majority of patients, who will never be resectable, the continuum of care with chemotherapy will be the paradigm for their management.

Surgical treatment for hepatocellular carcinoma in cirrhotic patients. Guide to the selection and decision-making process in a context of multimodal strategy.

Hepatocellular carcinoma (HCC) is the fifth most frequent malignant tumour and the third leading cause of death due to cancer worldwide [1]. Surgical treatment is the only long-term curative therapy. But the resection rate remains low in cirrhotic patients due to contraindications imposed mainly by hepatic insufficiency and excessively advanced tumoral stages. In recent years, however, due to the extended use of screening programmes in high-risk patients, tumours are smaller at presentation, making treatments easier. In the current context of shortage of organs for transplantation, surgical resection remains the best available treatment option for most patients with HCC in cirrhotic livers. Despite the encouraging results reported by several groups in terms of overall survival, the high recurrence rate is still an unsolved problem. Recently, a large, randomised, placebo-controlled trial has shown that a multikinase inhibitor targeting Ras-kinase and VEGFR-2, sorafenib, improves survival of patients with advanced HCC. Sorafenib was approved by regulatory agencies during 2007 and is likely to become the new standard therapy for HCC patients with advanced disease.

Customized birthweight standards for a Spanish population.

OBJECTIVE: To analyse the biological factors affecting birthweight and to derive customized birthweight standards for a Spanish population. METHODS: A retrospective cohort was created with all the singleton pregnancies delivered at term and free of pathology in our Institution. Birthweight was modeled by multiple linear regression from maternal (ethnic origin, maternal height, booking weight, smoking, and parity), and fetal (gender, gestational age) characteristics. RESULTS: In addition to gestational age and sex, height, booking weight, ethnic origin, parity, and smoking all have significant and independent effects on birthweight. Women from East-Asia, Morocco and South-America had newborns on average 83 g, 74 g and 95 g heavier than White-European Spanish women. The effect of smoking was found to be dose-related. CONCLUSION: We found the relative effect of the maternal and fetal characteristics to be very similar to that reported in previous studies. We report coefficients for ethnic groups that account for a sizeable proportion of the population composition of several European countries.

Guidelines for the detection and treatment of liver metastases of colorectal cancer.

The spread of the surgical treatment for hepatic metastases have been crucial in the improvement of treatment and survival of metastatic colorectal cancer. The early and accurate diagnosis of metastases and the assessment of their size are essential factors to reach the optimal results with this treatment strategy. The precise indication of the surgical technique with or without the previous administration of neoadjuvant chemotherapy is of significant importance for the choice of R0 surgery and the timing of intervention. Although there is an agreement regarding some parameters related to diagnosis techniques and surgical criteria such as the bilobar extension, the size of the remaining liver post-surgical removal and the indication of pre-operatory chemotherapy, it is necessary to consider all these factors to set up standard criteria and optimize the results. In this article we review all these parameters, from disease follow up to detect metastatic dissemination to the basic criteria for use of neoadjuvant chemotherapy, in order to suggest some general recommendations of evidence level II and recommendation grade A.

Effect of surgical resection of metastatic disease on immune tolerance to cancer. How a systemic disease could be controlled by a local therapy.

Surgery represents the only chance of cure for patients with colorectal liver metastases. The results of expanded indications for surgical treatment revealed that even advanced disease can be cured in a significant percentage of cases. What is the explanation for this systemic impact of a local treatment such as surgery? What is different in those patients who can be cured by resection? In this review we analyse the available evidence of the complex relationship between the growing tumour and the immune system. Special attention is directed to the role of T regulatory cells (Tregs) recruited by the tumour to construct a tolerogenic microenvironment in which to grow. Based on the published data we developed the hypothesis that surgery breaks the tumour immune tolerance status because it not only removes the tumour, but also the protective shield of T regulatory cells.

Surgical treatment of liver metastases from colorectal carcinoma in elderly patients. When is it worthwhile?

BACKGROUND: The elderly are under-represented in series of patients operated on for colorectal liver metastases (LM). OBJECTIVE: To analyse the influence of age on surgery of colorectal LM, and the identification of factors that could be used as exclusion criteria. PATIENTS AND METHODS: Six hundred and forty-eight patients underwent liver resection between 1990 and 2006. Demographic data, primary tumour related variables, stage of the disease, morbidity, mortality, survival and recurrence were prospectively recorded. RESULTS: One hundred and sixty of 648 patients (25%) were 70 years old or older. Postoperative mortality was significantly higher in elderly patients (8% vs. 3%, p=0.008). Morbidity was also higher (41% vs. 34%, p=0.008). Survival rate at 1, 3 and 5 years was 88%, 62% and 45% respectively in patients younger than 70 years, and 82%, 48% and 36% in the elderly (p=0.007). Excluding the postoperative mortality, the figures were 90%, 64% and 46%. 90%, 53% and 38% (p=0.061). Disease-free survival rates at 1, 3 and 5 years excluding postoperative mortality were 68%, 32% and 25% in younger patients, compared to 68%, 34% and 30% (p=0.71) in the elderly. Major liver resections increased mortality in the elderly. In the multivariate analyses only a tumour size equal to or more than 10 cm significantly increased the postoperative mortality risk in elderly patients. CONCLUSIONS: The elderly have a higher mortality. In recent years that difference has been markedly reduced. Excluding the postoperative mortality, the overall survival and disease-free survival are similar between both groups. The criteria to indicate surgery must be the same in both groups.

Colecistitis agudas: Actuales bases etiológicas, diagnósticas y terapéuticas

La colecistitis aguda es una de las patologías más frecuentes en el ámbito de la Cirugía de Urgencias. A pesar de la generalización de la colecistomía como tratamiento de la litiasis vesicular, el porcentaje de colecistitis agudas no ha variado durante los últimos años. Los autores revisan las características clínicas y diagnósticas de esta enfermedad así como los nuevos conceptos en el tratamiento de la misma, y exponen su propia experiencia en esta patología.

Insuficiencia renal aguda del recien nacido. / Acute Kidney failure of the newborn infant

Los autores presentan su experiencia en la insuficiencia renal aguda durante el periodo neonatal. Se resalta su relacion con la edad gestacional, mas frecuente cuanto menor es esta. Las causas fundamentales han sido en los preterminos aquellas que originan hipoxia (anoxia neonatal, neumopatias, apneas, etc.) y en los recien nacidos a terminos aquellas que originan hipovolemia, sobre todo la deshidratacion hipernatremica. Terapeuticamente, en una fase inicial se debe forzar la diuresis y posteriormente en aquellos casos en que no tiene lugar la crisis diuretica la practica de una dialisis peritoneal, la cual es mejor tolerada por los pretermino al presentar menores complicaciones