Pascual Parrilla

Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer

The laparoscopic treatment of rectal cancer is controversial. This study compared surgical outcomes after laparoscopic and open approaches for mid and low rectal cancers.

Laparoscopic Versus Open Gastric Bypass in the Treatment of Morbid Obesity: A Randomized Prospective Study

Objective:The objective of the study was to compare the results of open versus laparoscopic gastric bypass in the treatment of morbid obesity. Summary Background Data:Gastric bypass is one of the most commonly acknowledged surgical techniques for the management of morbid obesity. It is usually performed as an open surgery procedure, although now some groups perform it via the laparoscopic approach. Patients and Methods:Between June 1999 and January 2002 we conducted a randomized prospective study in 104 patients diagnosed with morbid obesity. The patients were divided into 2 groups: 1 group with gastric bypass via the open approach (OGBP) comprising 51 patients, and 1 group with gastric bypass via the laparoscopic approach (LGBP) comprising 53 patients. The parameters compared were as follows: operating time, intraoperative complications, early (<30 days) and late (>30 days) postoperative complications, hospital stay, and short-term evolution of body mass index. Results:Mean operating time was 186.4 minutes (125–290) in the LGBP group and 201.7 minutes (129–310) in the OGBP group (P < 0.05). Conversion to laparotomy was necessary in 8% of the LGBP patients. Early postoperative complications (<30 days) occurred in 22.6% of the LGBP group compared with 29.4% of the OGBP group, with no significant differences. Late complications (>30 days) occurred in 11% of the LGBP group compared with 24% of the OGBP group (P < 0.05). The differences observed between the 2 groups are the result of a high incidence of abdominal wall hernias in the OGBP group. Mean hospital stay was 5.2 days (1–13) in the LGBP group and 7.9 days (2–28) in the OGBP group (P < 0.05). Evolution of body mass index during a mean follow-up of 23 months was similar in both groups. Conclusions:LGBP is a good surgical technique for the management of morbid obesity and has clear advantages over OGBP, such as a reduction in abdominal wall complications and a shorter hospital stay. The midterm weight loss is similar with both techniques. One inconvenience is that LGBP has a more complex learning curve than other advanced laparoscopic techniques, which may be associated with an increase in postoperative complications.

Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.

Conservative treatment versus antireflux surgery in Barrett's oesophagus: long-term results of a prospective study.

The results obtained for the treatment of 59 patients diagnosed with Barretts oesophagus, randomized to receive medical treatment (n = 27) or antireflux surgery (n = 32) were assessed prospectively. Median follow‐up for the patients undergoing medical treatment was 4 (range 1–11) years and for patients undergoing surgical treatment 5 (range 1–11) years. Satisfactory symptomatic control (excellent to good results) was achieved in 24 patients after medical therapy and in 29 after antireflux surgery. The proportion of patients with persistent inflammatory lesions (54 per cent) and persistent or recurrent stenosis (47 per cent) was significantly higher after conservative treatment than after surgery (5 and 15 per cent, respectively). A decrease in the length of the segment of columnar mucosa was observed in eight of the patients who underwent antireflux surgery, and in only two of those given medical therapy. Conversely, an upward progression of the columnar lining was more frequent in the latter group (11 versus three). Mild dysplasia was observed in five patients, all from the group undergoing medical treatment. Severe dysplasia was detected in two patients, one undergoing medical treatment and the other following surgical therapy, in whom an antireflux procedure had failed previously. Both patients underwent oesophageal resection, with confirmation of a carcinoma in situ. The patients in whom antireflux surgery proved effective showed no dysplastic change or progression to adenocarcinoma. These results, despite the small number of patients and methodological limitations, question the systematic conservative approach in the initial management of patients with Barretts oesophagus.

Prospective Study of Postoperative Complications After Total Thyroidectomy for Multinodular Goiters by Surgeons With Experience in Endocrine Surgery

Objetives:(1) To show that total thyroidectomy (TT) can be performed in multinodular goiter (MG) by surgeons with experience in endocrine surgery with a definitive complication rate of 1% or less; and (2) to analyze the risk factors for complications in these patients. Summary Background Data:There is current controversy over the role of TT in the treatment of MG; although there are potential benefits, high rates of complications are not acceptable in surgery for a benign pathology. Patients and Method:A prospective study was conducted on 301 MGs meeting the following criteria: (1) bilateral MG; (2) no prior cervical surgery; (3) operation by surgeons with experience in endocrine surgery; (4) no associated parathyroid pathology; (5) no initial thoracic approach; and (6) minimum follow-up of 1 year. Age, sex, time of evolution, symptoms, cervical goiter grade, intrathoracic component, thyroid weight, and presence of associated carcinoma were analyzed as risk factors for complications. The χ2 test and a logistic regression analysis were applied. Results:Complications were presented by 62 patients (21%), corresponding to 29 hypoparathyroidisms, 26 recurrent laryngeal nerve injuries, 4 lesions of the superior laryngeal nerve, 3 cervical hematomas, and 1 infection of the cervicotomy. The variables associated with the presence of these complications were hyperthyroidism (P = 0.0033), compressive symptoms (P = 0.0455), intrathoracic component (P = 0.0366), goiter grade (P = 0.0195), and weight of excised specimen (P = 0.0302); hyperthyroidism (relative risk [RR] 2.5) and intrathoracic component (RR 1.5) persisted as independent risk factors. Definitive complications appeared in 3 patients (1%), corresponding to 2 hypoparathyroidisms and 1 recurrent laryngeal nerve injury. Two cases corresponded to a toxic goiter, and the third to an intrathoracic goiter with compressive symptoms. Conclusion:In endocrine surgery units, TT can be performed for MG with a definitive complication rate of around 1%; the main independent risk factors for the development of complications are hyperthyroidism and goiter size.

Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus.

ObjectiveTo compare the results of medical treatment and antireflux surgery in patients with Barrett’s esophagus (BE). Summary Background DataThe treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question. MethodsOne hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1–18) in the medical treatment group and 6 years (range 1–18) in the surgical treatment group. ResultsSatisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery. ConclusionsThese results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus.

Spanish Experience in Liver Transplantation for Hilar and Peripheral Cholangiocarcinoma

Objective:To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival. Summary Background Data:Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs. Methods:We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival. Results:The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III–IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma. Conclusions:OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.

Tranexamic Acid Reduces Red Cell Transfusion Better than ε-aminocaproic Acid or Placebo in Liver Transplantation

We evaluated the efficacy of the prophylactic administration of &egr;-aminocaproic acid and tranexamic acid for reducing blood product requirements in orthotopic liver transplantation (OLT) in a prospective, double-blinded study performed in 132 consecutive patients. Patients were randomized to three groups and given one of three drugs prophylactically: tranexamic acid, 10 mg · kg−1 · h−1; &egr;-aminocaproic acid, 16 mg · kg−1 · h−1, and placebo (isotonic saline). Perioperative management was standardized. Coagulation tests, thromboelastogram, and blood requirements were recorded during OLT and in the first 24 h. There were no differences in diagnosis, Child score, or preoperative coagulation tests among groups. Administration of packed red blood cells was significantly reduced (P = 0.023) during OLT in the tranexamic acid group, but not in the &egr;-aminocaproic acid group. There were no differences in transfusion requirements after OLT. Thromboembolic events, reoperations, and mortality were similar in the three groups. Prophylactic administration of tranexamic acid, but not &egr;-aminocaproic acid, significantly reduces total packed red blood cell usage during OLT. Implications In a randomized study of 132 consecutive patients undergoing liver transplantation, we found that tranexamic acid, but not &egr;-aminocaproic acid, reduced intraoperative total packed red blood cell transfusion.

Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days

Background. It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates. Methods. Five orthotopic liver xenotransplants from pig to baboon were carried out: three from unmodified pigs and two using livers from h-DAF transgenic pigs. Findings. The three control animals transplanted with livers from unmodified pigs survived for less than 12 hr. Baboons transplanted with livers from h-DAF transgenic pigs survived for 4 and 8 days. Hyperacute rejection was not detected in the baboons transplanted with hDAF transgenic pig livers; however, it was demonstrated in the three transplants from unmodified pigs. Baboons transplanted with livers from h-DAF transgenic pigs were extubated at postoperative day 1 and were awake and able to eat and drink. In the recipients of hDAF transgenic pig livers the clotting parameters reached nearly normal levels at day 2 after transplantation and remained normal up to the end of the experiments. In these hDAF liver recipients, porcine fibrinogen was first detected in the baboon plasma 2 hr postreperfusion, and was present up to the end of the experiments. One animal was euthanized at day 8 after development of sepsis and coagulopathy, the other animal arrested at day 4, after an episode of vomiting and aspiration. The postmortem examination of the hDAF transgenic liver xenografts did not demonstrate rejection. Interpretation. The livers from h-DAF transgenic pigs did not undergo hyperacute rejection after orthotopic xenotransplantation in baboons. When HAR is abrogated, the porcine liver maintains sufficient coagulation and protein levels in the baboon up to 8 days after OLT.

FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression withdrawal.

Background. Human liver allografts do sometimes survive in a recipient after withdrawal of immunosuppression (IS), commonly referred to as “operational tolerance.” Preliminary clinical data have suggested an increase in the frequency of regulatory T cells (Treg) CD4+CD25high and FoxP3 expression in operationally tolerant liver transplant recipients (Gr-T). In the context of human liver transplantation, the dynamics of Treg have not been studied. We designed a prospective study to ascertain the profile of the Treg population and FoxP3 expression during IS withdrawal. Methods. To identify such parameters, we analyzed peripheral blood mononuclear cell populations and FoxP3 mRNA expression in 12 liver allograft recipients under cyclosporine A-based IS, who showed stable function of the allograft for more than 2 years. Results. An increase was observed in the frequency of CD4+CD25high cells when the IS was withdrawn in Gr-T patients (n=5). These patients exhibited a 3.5-fold increase for relative mRNA FoxP3 expression before the complete IS withdrawal and this continued when IS therapy was stopped. In patients who suffered rejection (n=7) there was no increase in the CD4+CD25high cells or FoxP3 expression. Conclusions. With the present study, the first evidence is provided that the increase of CD4+CD25high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.