Higher metastatic efficiency of KRas G12V than KRas G13D in a colorectal cancer model.

Although all KRas (protein that in humans is encoded by the KRas gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared the metastatic efficiency of KRas G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) and KRas G13D (Kirsten rat sarcoma viral oncogene homolog with aspartic mutation at codon 13) oncogenes in an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones of the SW48 CRC cell line [Kras wild-type (Kras WT)] expressing the KRas G12V or KRas G13D allele were microinjected in the mouse cecum. The percentage of animals developing lymph node metastasis was higher in KRas G12V than in KRas G13D mice. Microscopic, macroscopic, and visible lymphatic foci were 1.5- to 3.0-fold larger in KRas G12V than in KRas G13D mice (P < 0.05). In the lung, only microfoci were developed in both groups. KRas G12V primary tumors had lower apoptosis (7.0 ± 1.2 vs. 7.4 ± 1.0 per field, P = 0.02), higher tumor budding at the invasion front (1.2 ± 0.2 vs. 0.6 ± 0.1, P = 0.04), and a higher percentage of C-X-C chemokine receptor type 4 (CXCR4)-overexpressing intravasated tumor emboli (49.8 ± 9.4% vs. 12.8 ± 4.4%, P < 0.001) than KRas G13D tumors. KRas G12V primary tumors showed Akt activation, and ß5 integrin, vascular endothelial growth factor A (VEGFA), and Serpine-1 overexpression, whereas KRas G13D tumors showed integrin ß1 and angiopoietin 2 (Angpt2) overexpression. The increased cell survival, invasion, intravasation, and specific molecular regulation observed in KRas G12V tumors is consistent with the higher aggressiveness observed in patients with CRC expressing this oncogene.

Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4+ colorectal cancer models.

Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4+ tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4+ tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier.

Predicting the pathological features of the mesorectum before the laparoscopic approach to rectal cancer.

Pelvic anatomy and tumour features play a role in the difficulty of the laparoscopic approach to total mesorectal excision in rectal cancer. The aim of the study was to analyse whether these characteristics also influence the quality of the surgical specimen. We performed a prospective study in consecutive patients with rectal cancer located less than 12 cm from the anal verge who underwent laparoscopic surgery between January 2010 and July 2013. Exclusion criteria were T1 and T4 tumours, abdominoperineal resections, obstructive and perforated tumours, or any major contraindication for laparoscopic surgery. Dependent variables were the circumferential resection margin (CMR) and the quality of the mesorectum. Sixty-four patients underwent laparoscopic sphincter-preserving total mesorectal excision. Resection was complete in 79.1% of specimens and CMR was positive in 9.7%. Univariate analysis showed tumour depth (T status) (P = 0.04) and promontorium-subsacrum angle (P = 0.02) independently predicted CRM (circumferential resection margin) positivity. Tumour depth (P < 0.05) and promontorium-subsacrum axis (P < 0.05) independently predicted mesorectum quality. Multivariate analysis identified the promontorium-subsacrum angle (P = 0.012) as the only independent predictor of CRM. Bony pelvis dimensions influenced the quality of the specimen obtained by laparoscopy. These measurements may be useful to predict which patients will benefit most from laparoscopic surgery and also to select patients in accordance with the learning curve of trainee surgeons.

[Laparoscopic approach of achalasia. Long-term clinical and functional results and quality of life]. / Abordaje laparoscópico de la acalasia. Resultados clínicos, de calidad de vida y funcionales a largo plazo.

INTRODUCTION: Laparoscopic Heller myotomy has become the gold standard procedure for patients with achalasia. This study evaluates the clinical status, quality of life, and functional outcomes after laparoscopic Heller myotomy. MATERIAL AND METHODS: We analyzed patients who underwent laparoscopic Heller myotomy with an associated anti-reflux procedure from October 1998 to December 2010. Before surgery, we administered a clinical questionnaire and as of 2002, we also evaluated quality of life using a specific questionnaire (GIQLI). In 2011, we performed a follow up for all available patients. We administered the same clinical questionnaire and quality of life test as before surgery and performed manometry and 24-hour pH monitoring. According to the length of follow up, patients were divided into 3 groups. Group 1 with a follow-up between 6 and 47 months; group 2 follow-up between 48 and 119 months, and group 3 with a follow-up of more than 120 months). Moreover, 27 patients had already been evaluated with this same protocol in 2003. Pre- and postoperative data were compared for the 3 groups and for patients who completed follow up in 2003 and 2011. RESULTS: Ninety-five patients underwent laparoscopic Heller myotomy. Seventy-six (80%) were available for follow-up. Mean follow-up was 56 months (range 6-143). Global improvement in dysphagia was 89%. Total DeMeester score decreased in the 3 groups. GIQLI scores improved after surgery, reaching normal values. Manometric determinations showed normal LES pressures after myotomy in the 3 groups. Ten percent of overall 24-hour pH monitoring was abnormal. The group of patients followed up in 2003 and in 2011 showed no impairment in the variables studied in the long term. CONCLUSIONS: Long-term follow up of the laparoscopic approach to achalasia showed good results concerning clinical status and quality of life, with normal sphincteric pressures and a low incidence of gastroesophageal reflux.

Minimally invasive therapy for epiphrenic diverticula: Systematic review of literature and report of six cases.

INTRODUCTION: Epiphrenic diverticula (ED) are infrequent and conventional surgical treatment entails aggressive open or transthoracic surgery. Minimally invasive treatment has changed the surgical approach but some surgical controversies are not resolved. OBJECTIVE: The objective of this study is to describe our experience in minimally invasive treatment of the ED and to perform a systematic review of the current literature in this subject. MATERIALS AND METHODS: We reviewed all data from the Hospital de Sant Pau, focusing on patients that underwent minimally invasive treatment for an ED since 1998 to date. Furthermore, we performed a systematic literature review focused on the minimally invasive approach for ED. RESULTS: A total of 6 patients have been treated (5 transhiatal and 1 with abdominal and thoracic approach). We found a predominance of males with a median age of 63. The diagnosis was made with an endoscopy, barium swallow and manometry. Half of the manometry results were pathologic. The surgical technique involved a diverticulectomy, myotomy and a Dor partial founduplication. Two patients that presented suture line leakage (SLL) were treated conservatively. No mortality was reported. The systematic review was carried out under the Preferred Reporting Items for Systematic Reviews and Meta-analyses scheme, with a total of 20 studies where 189 patients were found. No comparative or prospective randomised trials were found. Overall morbidity was 24%, with a SLL rate of 12%, hospital stay of 5 days and mortality of 1.5%. After a median follow-up of 42 months, 81.5% of the patients were asymptomatic. CONCLUSION: The minimally invasive approach for ED is a safe and feasible procedure.

A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement.

Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of ß1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement.

Single incision versus reduced port splenectomy--searching for the best alternative to conventional laparoscopic splenectomy.

BACKGROUND: Laparoscopic splenectomy (LS) is a well accepted approach for the treatment of multiple hematologic diseases. Single port access splenectomy (SPAS) emphasizes the concept of surgery through one small incision. The reduced port access splenectomy (RPAS) entails the use of fewer trocars of smaller sizes. The aim of this study was to compare the clinical outcomes after LS, SPAS, and RPAS, and to analyze the aesthetic result and patient satisfaction. METHODS: We included patients who underwent LS (group 1, n = 15), SPAS (group 2, n = 8), and RPAS (group 3, n = 10) between June 2008 and February 2012, whose final spleen weight was less of 500 g. The outcome parameters analyzed were operative time, need of additional trocars, blood loss, blood transfusion, weight of the spleen, postoperative complications, and duration of hospital stay. To evaluate the cosmetic result, patients were asked to take the Body Image Questionnaire. RESULTS: Patients in group 3 were younger than group 1. Operative time was significantly longer in group 2 compared to groups 1 and 3 (83 ± 19 vs. 131 ± 43 vs. 81 ± 22 min, p = 0.01). There was no need to convert to open surgery in any group, nor were there differences in intra- or postoperative outcome. There were no differences between the groups in relation to the analgesic requirements. Twenty-two out of the 33 patients answered the questionnaire. There was a significant advantage in group 2 and 3 in the body image index with respect to group 1. There were no differences between groups 2 and 3 (7.3 ± 2.8 vs. 5.8 ± 1.3 vs. 5.1 ± 0.4, p < 0.02). CONCLUSIONS: RPAS is a good alternative to LS and SPAS. It improves the aesthetic results as compared to LS, whereas minimizes the technical challenges faced with SPAS.

Long-term outcome and quality of life after laparoscopic treatment of large paraesophageal hernia.

BACKGROUND: Laparoscopy has been widely used for surgical repair of large paraesophageal hernias (PEHs). The technique, however, entails substantial technical difficulties, such as repositioning the stomach in the abdominal cavity, sac excision, closure of the hiatal gap, and fundoplication. Knowledge of the long-term outcome (>10 years) is scarce. The aim of this article was to evaluate the long-term results of this approach, primarily the anatomic hernia recurrence rate and the impact of the repair on quality of life. METHODS: We identified all patients who underwent laparoscopic repair for PEH between November 1997 and March 2007 and who had a minimum follow-up of 48 months. In March 2011, all available patients were scheduled for an interview, and a radiologic examination with barium swallow was performed. During the interview the patients were asked about the existence/persistence of symptoms. An objective score test, the gastrointestinal quality of life index (GIQLI), was also administered. RESULTS: A total of 77 patients were identified: 17 men (22 %) and 60 women (78 %). The mean age at the time of fundoplication was 64 years (range 24-87 years) and at the review time 73 years (range 34-96 years). The amount of stomach contained within the PEH sac was <50 % in 39 patients (50 %), >50 % in 31 (40 %), and 100 % (intrathoracic stomach) in 7 (9.5 %). A 360º PTFe mesh was used to reinforce the repair in six cases and a polyethylene mesh in three. In May 2011, 55 of the 77 patients were available for interview (71 %), and the mean follow-up was 107 months (range 48-160 months). Altogether, 43 patients (66 %) were asymptomatic, and 12 (21 %) reported symptoms that included dysphagia in 7 patients, heartburn in 3, belching in 1, and chest pain in 1. Esophagography in 43 patients (78 %) revealed recurrence in 20 (46 %). All recurrences were small sliding hernias (<3 cm long). In all, 37 patients (67 %) answered the GIQLI questionnaire. The mean GIQLI score was 111 (range 59-137; normal 147). Patients with objective anatomic recurrence had a quality of life index of 110 (range 89-132) versus 122 in the nonrecurrent hernia group (range 77-138, p < 0.01). Mesh was used to buttress the esophageal hiatus in nine patients. One patient died during the follow-up period. Five of the remaining eight patients (62 %) developed dysphagia, a mesh-related symptom. Three patients required reoperation because of mesh-related complications. Esophagography revealed recurrence in four (50 %) of the eight patients. GIQLI scores were similar in patients with recurrence (126, range 134-119) and without it (111, range 133-186) (p > 0.05). CONCLUSIONS: Long-term follow-up (up to 160 months) in our study showed that laparoscopic PEH repair is clinically efficacious but is associated with small anatomic recurrences in ≤50 % of patients. Further studies are needed to identify the anatomic, pathologic, and physiological factors that may impair outcome, allowing the procedure to be tailored to each patient.

[Hepatic resection in hepatocarcinoma: a comparative study between patients under and over 70 years-old]. / Resección hepática por hepatocarcinoma: estudio comparativo entre pacientes menores y mayores de 70 años.

INTRODUCTION: The ageing population raises concerns about the adequacy of aggressive surgical procedures and their outcomes. The treatment of the elderly with hepatocellular carcinoma is one of the diseases that involve complicated management decisions. We set out to compare the results between an older and younger patient cohort with this disease are compared. MATERIAL AND METHODS: A total of 36 hepatic resections were performed on patients with hepatocellular carcinoma between 2000 and 2011. The cohort was divided into 2 groups (14 patients < 70 and 22 patients ≥ 70 years of age), and their results, disease free and overall survival were compared using Kaplan-Meir curves and log rank test. An attempt was also made at determining the predictive factors of a poor outcome among this patient cohort. RESULTS: Both groups were similar with regards to their pre-operative status. Operation time, procedure, hospital stay, and morbidity and mortality were similar. Overall survival at 3 and 5 years comparing the younger vs. the elderly group was 85.7% vs. 68.7% and 47.6% vs. 60%, respectively (P=.813). Disease free survival at 3 and 5 years comparing the younger vs. the elderly group was 69.3% vs. 35.2% and 39.6% vs. 23.4%, respectively (P=.539). Multivariate analysis of the whole cohort revealed multicentric diseases and elevated alpha-fetoprotein as independent factors of poor disease free survival and overall survival, respectively. CONCLUSIONS: Elderly patients with hepatocellular carcinoma should be managed in a similar fashion to younger patients. Surgeons should expect similar post-operative complications, disease free and overall survival.

[Laparoscopic fundoplication results in the treatment of the non-gastrointestinal symptoms of gastroesophageal reflux]. / Resultados de la funduplicatura laparoscópica en el tratamiento de los síntomas extradigestivos del reflujo gastroesofágico.

INTRODUCTION: Gastroesophageal reflux disease (GERD) can trigger typical and atypical symptoms (cough, dysphonia, asthma…). GERD with typical symptoms has well established surgical indications, but it is not the case when the symptoms are atypical. Our aim is to assess the effectiveness of laparoscopic surgery in those patients in whom the surgical indication was mainly due to atypical symptoms. MATERIAL AND METHODS: Between 1998 and 2011 laparoscopic fundoplication was performed on of 318 patients with GERD, of whom 14 (4%) had atypical symptoms as the main indication. Typical symptoms were present in 12 (86%) cases, and atypical symptoms were: cough in 5 (36%) cases, respiratory symptoms 5 (36%), dysphonia 2 (14%), vocal chords granuloma 1 (7%) and larynx spasm 1 (7%). The GERD diagnosis was established due to evidence of an anatomical or functional alterations of the gastroesophageal junction (hiatus hernia, pathological manometry or pH-metry). The clinical histories of the patients were reviewed and they were given a gastrointestinal quality of life (Gastrointestinal Quality of Life Index [GIQoL]) questionnaire was completed, as well as a subjective assessment (0 to 4) of the modification of their atypical symptoms. RESULTS: A clinical improvement was observed in both the atypical and typical GERD in 12 patients (86%), with the symptoms score decreasing from 3.7 to 0.7. A significant improvement (P<.05) from the pre-surgical value 107(±26) to 122 (±10) points was obtained in the quality of life (GIQoL) in 11 patients (79%). CONCLUSION: Laparoscopic fundoplication is an effective technique in the treatment of the atypical symptoms of GERD.

[Medium term results on introducing colorrectal laparoscopic surgery into clinical practice after having an intensive training course]. / Resultados a medio plazo en la implementación de la cirugía laparoscópica colorrectal en la práctica clínica tras la realización de un curso intensivo.

INTRODUCTION: Endoscopic surgery has characteristics that increase the difficulties of learning. Five years ago, an intensive colorectal laparoscopic surgery course was designed to offer training in the technical bases of this type of surgery. The aim of this article is to determine the impact of the colorectal surgery course on clinical practice, and to investigate the factors that limit its applicability and the training preferences of the surgeons. MATERIAL AND METHODS: Twenty-two courses of four days duration, with 36 hours of lessons (4 in seminar form and 32 in the surgery), and with 7 trainees, were held between June 2005 and December 2010. A survey was sent out in December 2010 to assess the impact of the course on the colorectal laparoscopic surgery activity of the trainee, to find out the difficulties encountered in its application, and to evaluate the training expectations in endoscopic surgery in this group of surgeons. RESULTS: The questionnaire was sent to 148 surgeons, with 74 (50%) responses received. The mean period after the course was 26.5 (2-60) months. A monthly increase of more than 5 cases was observed in 70% of the centres. The course enabled them to consolidate the activity in local hospitals, while in university and general hospitals it served to re-launch an initial experience. Among the obstacles that made it difficult to introduce were care load and the availability of a surgeon, particularly in general and university hospitals (P=.001), and in local hospitals it was the availability of patients. The majority of surgeons (70%) believed that specific training was required, preferring a short period in a hospital with experience. CONCLUSIONS: An intensive course on colorectal laparoscopic surgery enabled the activity to be consolidated or increased in this area. Training in colorectal laparoscopic surgery requires additional teaching efforts, which are currently unstructured.

Laparoscopic rectal surgery: does immediate outcome differ in respect to sex?

PURPOSE: This study analyzed the immediate postoperative outcome of the laparoscopic approach to the rectum in relation to the sex of the patient. METHODS: Two hundred thirty-nine patients were included in our study. The inclusion criterion was rectal cancer <15 cm from the anal margin. Exclusion criteria were the presence of anesthetic contraindications for pneumoperitoneum, T4, pancolonic polyposis, and ulcerative colitis. The parameters analyzed included demographics, comorbidities, previous abdominal surgery, preoperative chemoradiotherapy, body mass index, operative time, type of operation, difficulty score, conversion, hospital stay, postoperative morbidity according to the Dindo classification, and histopathologic analysis. Analysis was performed on an intention-to-treat basis. Results are given as number of cases and percentages for categorical data, and as median and 95% confidence interval for quantitative variables. Data were analyzed by use of bivariate analysis, contingency tables, and chi or Fisher exact tests for categorical variables, and ANOVA or t test for quantitative variables. The statistical significance level was set at 5% (alpha = 0.05), and two-tailed tests were used throughout. RESULTS: We did not find any statistical differences related to sex in the global series, pure laparoscopy, or converted patients in relation to mortality, conversion, anastomotic leakage, morbidity, reintervention, and morbidity classification according to Dindo (P > .05). We only observed a trend in relation to a longer duration of surgery in men. This was statistically significant in the low anterior resection subgroup (P = .02) and in the overall series (P = .002). Statistical analysis also showed that postoperative stay was longer in men after an anterior resection (P = .015). CONCLUSION: We believe that no important differences exist in perioperative outcomes between men and women after a laparoscopic approach to rectum cancer.

Single incision approach for splenic diseases: a preliminary report on a series of 8 cases.

BACKGROUND: There is a current trend to reduce the invasiveness of minimally invasive procedures, and the single-incision laparoscopic approach (SILS) has been proposed for several intra-abdominal surgical interventions. The spleen poses specific problems for techniques, such as SILS, due to its volume and texture, and little clinical information is available on the topic. We describe our initial experience using SILS for the management of splenic diseases. METHODS: Between December 2008 and September 2009, we attempted SILS in eight patients: four men and four women with a median age of 44 (range, 26-73) years, and body mass index of 24.5 (range, 18-31). Preoperative diagnosis was malignancy (n = 3), ITP (n = 1), HIV-related hypersplenism (n = 1), spherocytosis (n = 1), and splenic cyst (n = 2). SILS was attempted transumbilically in four cases and through a 15-mm subcostal single incision in the other four. As entry port we used either three trocars (one of 12 mm and two of 5 mm) inserted through the single-site incision or the umbilicus, or a multiport (Triport, Olympus) device. Instrumentation used consisted of curved instruments, a flexible-tip 10-mm scope, and the harmonic scalpel. Visualization of the spleen and standard dissection of attachments was accomplished, and splenectomy was completed by stapling of the splenic hilum. The spleen was extracted through the single-site incision. In two cases, unroofing of a splenic cyst was performed transumbilically. RESULTS: The SILS procedure was successful in six of the eight patients (75%). Conversion to conventional laparoscopic splenectomy (LS) was required in two patients due to adhesions and spleen size. Median operative time was 97 (range, 60-150) min. There were no postoperative complications, and median stay was 4 (range, 2-5) days. Median spleen weight was 485 (range, 340-590) g. CONCLUSIONS: SILS access can be safely used for operative visualization, hilum transection, and spleen removal, further reducing parietal wall trauma. The definitive clinical, esthetic, and functional advantages require further analysis.

Single-port access: a feasible alternative to conventional laparoscopic splenectomy.

HYPOTHESIS: The laparoscopic approach has become the gold standard for splenectomy despite the fact that the spleen is a solid organ located deep in the splenic fossa. There is currently a trend to reduce the invasiveness of minimally invasive procedures. Transabdominal or transumbilical single-incision laparoscopic (SILS) approaches are an alternative to natural orifice transluminal endoscopic surgery techniques, but no reports of their use have yet been published in relation to the spleen. AIM: To describe the SILS technique for splenectomy in 2 patients. MATERIAL AND METHODS: Two patients were approached by SILS, a 26-year-old male diagnosed of autoimmune thrombocytopenia and a 45-year-old male with recurrent Hodgkin disease. In both cases 3 trocars (1 of 12 mm and 2 of 5 mm) were inserted through the umbilicus in one and in a left subcostal in the other, and a curved transanal endoscopic microsurgery instrument, a flexible-tip 10-mm scope, and the UltraCision were introduced. Visualization of the spleen and standard dissection of attachments were feasible, and splenectomy was completed using transumbilicus stapling of the splenic hilum. The spleen was extracted through the umbilical incision, intact in one case and after morcellation in the other. RESULTS: The postoperative course was uneventful. Both patients had minimal postoperative pain and scarring and were discharged on the second postoperative day. CONCLUSIONS: SILS access can be safely used for operative visualization, hilum transection, and spleen removal with conventional instrumentation, reducing parietal wall trauma to a minimum. The clinical, esthetic, and functional advantages require further analysis.

[Surgical treatment of achalasia: Better than dilations?]. / Tratamiento quirúrgico de la acalasia: ¿mejor que las dilataciones?

Achalasia is an infrequent esophageal disease that severely impairs the quality of life of affected individuals. The etiology of this entity is not well defined and its main clinical features are dysphagia and regurgitation. The treatment of achalasia continues to be palliative and is aimed at providing functional and symptomatic relief through opening of the lower esophageal sphincter. The present article describes and evaluates the medical and surgical treatments most commonly used in clinical practice after the introduction of minimally invasive surgery, which has represented an important addition to the therapeutic alternatives. Currently, the most appropriate initial option is laparoscopic surgery, while pneumatic dilatation and botulinum toxin injection should be reserved for selected patients.

[Laparoscopic treatment of rectal prolapse]. / Tratamiento laparoscópico del prolapso rectal.

INTRODUCTION: Rectal prolapse is an uncommon disease mainly seen in patients of advanced age. It is treated surgically, although there is still significant controversy as regards the most appropriate technique. In the last few years the laparoscopic route has been shown to be feasible and has the advantage of being a minimally invasive technique. OBJECTIVE: To present the preliminary results of a series of patients with rectal prolapse, the majority of whom were treated by performing a laparoscopic posterior rectopexy. MATERIAL AND METHOD: Between February 1998 and February 2008, 17 patients diagnosed with total rectal prolapse were operated on. In 15 cases, a Wells type posterior rectopexy was performed and in the other two a sigmoidectomy was done. The pre-surgical characteristics, as well as the immediate post-surgical results and the long-term follow up results were analysed. RESULTS: The mean age of the series was 63 (21-87) years, with a mean operation time of 186 (105-240) min and a conversion index of 6.6%. There was no post-surgical morbidity and mortality and the mean hospital stay was 5.2 (3-8) days. The mean follow-up was 39 (6-96) months with no relapses seen. One patient had an intralumen migration of the mesh which was expulsed via the rectum, two years after the surgery. One patient died during follow-up due to his underlying severe cardio-respiratory disease. The prolapse re-occurred in one patient after a sigmoidectomy. Eight patients (53%) previously had constipation and in six cases (40%), incontinence. In the post-surgical reviews, constipation persisted in three patients (20%) and a it was seen de novo in one case (6.6%). The incontinence was resolved in four cases (26%) and persisting in two patients (13%). CONCLUSIONS: Laparoscopic rectopexy is a good technical option with a low morbidity-mortality and a reduced hospital stay, as well as good results in the long-term.

Lower specific micronutrient intake in colorectal cancer patients with tumors presenting promoter hypermethylation in p16(INK4a), p4(ARF) and hMLH1.

BACKGROUND: The diversity of the Mediterranean diet and the heterogeneity of acquired epigenetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and promoter hypermethylation in genes implicated in the pathogenesis of these neoplasms (p16(INK4a), p14(ARF), hMLH1) and the interaction with methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism. PATIENTS AND METHODS: For the molecular study, 120 CRC patients were analyzed for hMLH1 promoter methylation status and MTHFR genotyping. Dietary patterns and molecular data on p16(INK4a) and p14(ARF) methylation were obtained from previous studies with this populations. RESULTS: Patients with methylation in p16(INK4a) consumed significantly less folate (p = 0.01), vitamin A (p = 0.01), vitamin B1 (p = 0.007), potassium (p = 0.03) and iron (p = 0.02) than controls. Patients with methylation in p14(ARF) or hMLH1 consumed significantly less vitamin A (p = 0.001 and p = 0.05, respectively). CONCLUSION: These results support that certain micronutrients protect against colorectal neoplasia and emphasize the importance of considering the different molecular forms of CRC as etiologically distinct diseases.

Codon 12 and codon 13 mutations at the K-ras gene induce different soft tissue sarcoma types in nude mice.

K-ras codon 12 mutation is more oncogenic in in vitro and in vivo experimental systems than K-ras codon 13 mutation. Moreover, human colorectal tumors bearing a codon 12 mutation are more aggressive, invasive, and metastatic than the same tumor types carrying a codon 13 mutation. However, despite the association between specific sarcoma types and codon 12 or codon 13 mutations, the relationship between the position of the mutated codon at ras genes and tumor aggressiveness has not been studied in this tumor type. Here, we used a nude mice model to evaluate the tumorogenic capacity of stable transfectants of NIH3T3 fibroblasts, expressing K-ras mutated at codon 12 (K12) or 13 (K13), and morphologically, functionally, and molecularly compared these tumors. We found histopathological differences between them, K12-derived tumors showing fibrosarcoma-like features, whereas K13-derived tumors resembled malignant fibrous histiocytomas. Moreover, K12 tumors showed shorter latency of appearance, lower apoptotic and mitotic rates, and higher expression of markers for sarcoma aggressiveness (Ki67, p53 and c-myc) than K13 tumors. They also showed differences in the expression or activation of Ras, Ras downstream pathways [c-Jun N-terminal kinase (JNK), MAPK and AKT], and apoptotic [AKT, Bcl-2, Focal adhesion kinase (FAK)] and mitotic (cyclin B1) regulators, which could explain their functional differences. Most remarkably, the significantly diminished apoptotic rate observed in K12-derived tumors was associated with enhanced antiapoptotic signaling through the AKT pathway. These morphological, functional, and molecular differences demonstrate that codon 12 and codon 13 mutations in the K-ras oncogene can induce two different soft tissue sarcoma types in our in vivo model.