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Manuel Trias

Publications and source records attributed to Manuel Trias.

18 recordsLinked to original sources

Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is effective as chemopreventive against colon cancer and it is the only nonsteoroidal antiinflammatory drug approved by the FDA for adjuvant therapy in patients with familial adenomatous polyposis. It is also being evaluated, within Phase II and III clinical trials, in combination with standard chemotherapy to treat sporadic colorectal cancer. Nevertheless, its antitumor mechanism of action is still not fully understood. In this study, we have evaluated the in vitro growth inhibitory effect of celecoxib in colon carcinoma cells and analyzed its mechanism of action. We report that the deregulation of the focal adhesion assembly protein Crk-associated substrate 130 kDa (p130Cas) by celecoxib plays a relevant role in the cytotoxic effect of this drug. Thus, celecoxib induces the proteolysis of p130Cas and the nuclear translocation of the 31 kDa generated fragment leading to apoptosis. Furthermore, overexpression of wild-type p130Cas reverts, in part, the growth inhibitory effect of celecoxib. In contrast, FAK and AKT do not appear to be involved in this activity. Our data suggest, for the first time, that the antitumor mechanism of action of celecoxib includes the induction of anoikis, an effect that is not related to COX-2 inhibition. Besides providing new insights into the antitumor effect of celecoxib, this novel mechanism of action holds potential relevance in drug development. Indeed, our results open the possibility to develop new celecoxib derivatives that induce anoikis without COX-2 inhibition so as to avoid the cardiovascular toxicity recently described for the COX-2 inhibitors.

Anoikis↗

K-ras Asp12 mutant neither interacts with Raf, nor signals through Erk and is less tumorigenic than K-ras Val12.

Different mutant amino acids in the Ras proteins lead to distinct transforming capacities and different aggressiveness in human tumors. K-Ras Asp12 (K12D) is more prevalent in benign than in malignant human colorectal tumors, whereas K-Ras Val12 (K12V) associates with more advanced and metastatic carcinomas, higher recurrence and decreased survival. Here, we tested, in a nude mouse xenograft model, whether different human K-Ras oncogenes mutated at codon 12 to Val, Asp or Cys would confer NIH3T3 fibroblasts distinct oncogenic phenotypes. We studied tumor histology and growth, apoptotic and mitotic rates, activation of signal transduction pathways downstream of Ras and regulation of the cell cycle and apoptotic proteins in tumors derived from the implanted transformants. We found that the K12V oncogene induces a more aggressive tumorigenic phenotype than the K12D oncogene, whereas K12C does not induce tumors in this model. Thus, K12V mutant tumors proliferate about seven times faster, and have higher cellularity and mitotic rates than the K12D mutant tumors. A molecular analysis of the induced tumors shows that the K12V mutant protein interacts with Raf-1 and transduces signals mainly through the Erk pathway. Unexpectedly, in tumors induced by the K12D oncogene, the K-Ras mutant protein does not interact with Raf-1 nor activates the Erk canonical pathway. Instead, it transduces signals through the PI3K/Akt, JNK, p38 and FAK pathways. Finally, the higher growth rate of the K12V tumors associates with enhanced Rb phosphorylation, and PCNA and cyclin B upregulation, consistent with faster G1/S and G2/M transitions, without alteration of apoptotic regulation.

Animals↗

[Immediate peritoneal response to contamination during laparoscopic surgery in an experimental mouse model].

INTRODUCTION: Several studies have shown that laparoscopic surgery (LS) minimizes surgical trauma and preserves immune response. Another advantage is the lower incidence of infectious complications. However, several in vitro studies have shown that an atmosphere with CO2 affects macrophage physiology, which would affect the response to peritoneal contamination. This observation is controversial, given the experimental evidence of a better conserved response to peritoneal contamination. The aim of the present study was to investigate the immediate response of the peritoneum to contamination in an atmosphere with CO2. MATERIAL AND METHOD: A total of 192 CD-1 rats were distributed into three groups: group I, LP, n= 64, (laparotomy); group II, LC-CO2, n= 64, (laparoscopy-CO2), group III, LC-T, n= 64, (laparoscopy-traction). The rats were randomized to receive 1 ml of a suspension of Escherichia coli (1x10(4) CFU/ml) (contamination [C]) or saline serum (no contamination [NC]). Peritoneal fluid was obtained at 1.5, 3, 6, and 12 h after surgery. Monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6 and prostaglandin.E2 (PGE2) were determined. RESULTS: MCP-1 levels were significantly higher and increased earlier in group II (LC-CO2-NC) than in group I (LP-NC) (p< .007). Simultaneously, the increase in the traction group was significantly higher (p< .002) than after laparotomy, without differences with respect to group II (LC-CO2-NC). When contamination was added, there was a significant increase in the three groups (p< .5). The modifications in MCP-1 in the LP-C group were statistically significantly greater and appeared earlier than those in the traction groups, LC-T-C (p< .002) and LC-CO2-C (p< .02). Interleukin 6: the three models showed a significant increase, which appeared later in the LP-NC group. Simultaneously, the increase in IL-6 appeared earlier and was significantly greater in the LC-T-NC group than in the LP group (p< .003), with no differences between the LC-CO2-NC and LC-T-NC groups. There was a significant difference between contaminated and uncontaminated groups in the LC-CO2 model. The traction model (LC-T-C group) showed a greater increase than the LP-C and LC-CO2-C groups (p< .001). PGE2: a significant increase was observed in the three models without contamination. However, when contamination was added, no differences were observed. CONCLUSION: Pneumoperitoneum with CO2 provokes a peritoneal response that is qualitatively different from open surgery and modifies the response to contamination with a greater increase in MCP-1 and IL-6.

Animals↗

Laparoscopic resection of clinically suspected gastric stromal tumors.

Gastrointestinal stromal tumors (GISTs) account for 5% of all gastric tumors. Preoperative diagnosis is relatively difficult because biopsy samples are rarely obtained during fibergastroscopy. Surgical radical resection is the gold standard treatment, allowing pathologic study for both diagnosis and prognosis. Laparoscopic resection has become an alternative to the open approach, but long-term results are not well known. The aim of this study is to report experience with laparoscopic resection, placing special emphasis on preoperative diagnosis and describing long-term results. A retrospective analysis was made of all patients undergoing a laparoscopic resection for clinically suspected gastrointestinal stromal tumors between November 1998 and August 2006 at 2 tertiary hospitals. The medical records of all participants were reviewed regarding surgical technique, clinicopathologic features, and postoperative long-term outcome. Laparoscopic gastric resection was attempted in 22 patients (13 women and 9 men) with a mean age of 66.7 years (range, 29-84 years). One patient had 2 gastric tumors. Tumor localization was upper gastric third in 6 patients, mid-gastric third in 7, and distal third in 10. Surgical techniques were transgastric submucosal excision (n = 1), wedge resection (n = 13), partial gastrectomy with Y-en-Roux reconstruction (n = 6), and total gastrectomy with Y-en-Roux reconstruction (n = 2). Two patients (9.1%) required conversion to the open procedure because of tumor size. Postoperative morbidity was delayed gastric emptying in 3 patients. Median postoperative stay was 6 days (range, 4-32 days). Pathologic and immunohistochemical study confirmed gastrointestinal stromal tumors in 18 cases. The other 4 cases were adenomyoma, hamartoma, plasmocytoma, and parasitic tumor (anisakis). Median tumor size was 5.6 cm (range, 2.5-12.5 cm) in cases of gastrointestinal stromal tumors. Malignant risk of gastrointestinal stromal tumors assessed according to mitotic index and size was low (n = 8), intermediate (n = 6), or high (n = 4). After a median follow-up of 32 months (range, 1-72 months), there was 1 case of recurrence of GIST. Definitive preoperative diagnosis of gastric submucosal tumors is frequently difficult. The laparoscopic approach to surgical treatment of these tumors seems safe and is associated with acceptable intermediate-term results, especially in cases of gastrointestinal stromal tumors.

Adult↗

[What has changed in adrenalectomy? From open surgery to laparoscopy?].

INTRODUCTION: After the introduction of the laparoscopic approach in adrenal surgery, this technique has become the gold standard in surgical adrenal diseases. Nevertheless, comparative studies with open surgery are scarce and the impact of laparoscopic techniques on these diseases is unknown. OBJECTIVE: To evaluate our experience of adrenal surgery over a 14-year period, before and after the introduction of laparoscopic adrenalectomy, and to analyze the influence of this technique on the surgical management of adrenal diseases. PATIENTS AND METHOD: From January 1990 to June 2004, 78 patients underwent adrenalectomy. Between 1990 and 1998, open adrenalectomy was performed in 24 patients, while between 1999 and 2004, 54 patients underwent the laparoscopic approach and 1 underwent open surgery. Data for the open group were retrospectively reviewed while those for the laparoscopic group were prospectively registered in the advanced laparoscopic surgery database of Hospital Sant Pau (HSP). RESULTS: The mean age was 47 years (16-75) in the open group and was 49 years (17-77) (p = NS) in the laparoscopic group. Distribution by surgical indication was similar in both periods concerning primary hyperaldosteronism, hypercortisolism, and pheochromocytoma, with a significant increase in surgical cases indicated by malignancy (1 vs 4) or incidentaloma (2 vs 13) (p<.001). Operating time was reduced from 150 min (65-210) in the open group to 90 min (30-300) in the laparoscopic group (p<.01). Morbidity was also reduced (20% vs 6%, p<.01). The size of lesions resected by open or laparoscopic surgery (4 cm [0.4-16] vs 3.5 cm [1.2-14]) was similar. The mean length of hospital stay was reduced from 8 days (3-13) to 3 days (2-12) (p<.01). The number of adrenalectomies performed in HSP was 24 in the first period (1990-1997) vs 40 in the second (1998-2004). This represented an increase from 3/year to 6.6/year mainly due to the increase in the number of incidentalomas. CONCLUSIONS: The laparoscopic approach has improved immediate surgical results (operating time, morbidity, and length of hospital stay). There was a clear increase in the number of adrenalectomies, and especially of incidentalomas, due to improved diagnostic techniques and the availability of a less aggressive approach.

Adolescent↗

[Intraductal papillary mucinous neoplasms of the pancreas].

INTRODUCTION: Mucin-producing pancreatic tumors account for 1% of all malignant tumors of the pancreas. Notable among these are intraductal papillary mucinous neoplasms of the pancreas, due to their variable clinical behavior, increased frequency, and the controversy surrounding the most suitable treatment and diagnostic methods. The aim of this study was to analyze the clinical presentation, epidemiological and pathological features, diagnostic methods, treatment and survival rates of these tumors. PATIENTS AND METHOD: We performed a prospective review of patients with a diagnosis of intraductal papillary mucinous neoplasm of the pancreas between 1996 and 2001. Demographic and clinical characteristics, diagnostic tests, surgical treatment, tumor characteristics and survival rates were studied. RESULTS: There were 8 patients. The mean age was 65 years. The most common clinical presentation was abdominal pain. The most frequent localization was the pancreatic head. The most common diagnostic methods used were abdominal computed tomography, endoscopic retrograde pancreatography, and serum CA 19.9 levels. Seven patients underwent pancreatic resection and only one patient was not surgically treated. The mean follow-up period was 38 months with a survival rate of 75% and a recurrence rate of 25%. CONCLUSION: Intraductal papillary mucinous neoplasms of the pancreas generally appear in the sixth decade of life. The most common presenting symptom is abdominal pain. These neoplasms typically occur in the head of the pancreas. The most commonly used diagnostic test is computed tomography and the main treatment is early surgical resection. The prognosis is good after complete resection, with a 5-year survival rate of 60-70%.

Adenocarcinoma, Mucinous↗

Energy sources for laparoscopic colectomy: a prospective randomized comparison of conventional electrosurgery, bipolar computer-controlled electrosurgery and ultrasonic dissection. Operative outcome and costs analysis.

The development of operative laparoscopic surgery is linked to advances in ancillary surgical instrumentation. Ultrasonic energy devices avoid the use of electricity and provide effective control of small- to medium-sized vessels. Bipolar computer-controlled electrosurgical technology eliminates the disadvantages of electrical energy, and a mechanical blade adds a cutting action. This instrument can provide effective hemostasis of large vessels up to 7 mm. Such devices significantly increase the cost of laparoscopic procedures, however, and the amount of evidence-based information on this topic is surprisingly scarce. This study compared the effectiveness of three different energy sources on the laparoscopic performance of a left colectomy. The trial included 38 nonselected patients with a disease of the colon requiring an elective segmental left-sided colon resection. Patients were preoperatively randomized into three groups. Group I had electrosurgery; vascular dissection was performed entirely with an electrosurgery generator, and vessels were controlled with clips. Group II underwent computer-controlled bipolar electrosurgery; vascular and mesocolon section was completed by using the 10-mm Ligasure device alone. In group III, 5-mm ultrasonic shears (Harmonic Scalpel) were used for bowel dissection, vascular pedicle dissection, and mesocolon transection. The mesenteric vessel pedicle was controlled with an endostapler. Demographics (age, sex, body mass index, comorbidity, previous surgery and diagnoses requiring surgery) were recorded, as were surgical details (operative time, conversion, blood loss), additional disposable instruments (number of trocars, EndoGIA charges, and clip appliers), and clinical outcome. Intraoperative economic costs were also evaluated. End points of the trial were operative time and intraoperative blood loss, and an intention-to-treat principle was followed. The three groups were well matched for demographic and pathologic features. Surgical time was significantly longer in patients operated on with conventional electrosurgery vs the Harmonic Scalpel or computed-based bipolar energy devices. This finding correlated with a significant reduction in intraoperative blood loss. Conversion to other endoscopic techniques was more frequent in Group I; however, conversion to open surgery was similar in all three groups. No intraoperative accident related to the use of the specific device was observed in any group. Immediate outcome was similar in the three groups, without differences in morbidity, mortality, or hospital stay. Analysis of operative costs showed no significant differences between the three groups. High-energy power sources specifically adapted for endoscopic surgery reduce operative time and blood loss and may be considered cost-effective when left colectomy is used as a model.

Adult↗

Minimally invasive treatment for obstructive tumors of the left colon: endoluminal self-expanding metal stent and laparoscopic colectomy. Preliminary results.

BACKGROUND: Obstruction of the left colon may be the first manifestation of colorectal cancer. Resection of the colonic segment involved and the construction of an end colostomy (Hartman's procedure) is the most frequent treatment. Alternatives to the placement of a stoma are subtotal colectomy or intraoperative lavage of the colon and primary anastomosis, but their application depends on intraoperative findings and the availability of a skilled surgeon. The use of an expandable stent (SEMS) can enhance the feasibility of laparoscopic colectomy, avoiding the need for a colostomy and offering the advantages of a combination of two minimally invasive procedures. STUDY DESIGN: Between 1997 and 2004, an SEMS was placed in 11 cases of left colonic obstruction due to cancer, the obstruction being successfully resolved in each case. Seven patients were approached by laparoscopy to attempt the definitive colectomy. We evaluated the location and pathological characteristics of the tumor, effectiveness and complications of SEMS insertion, time interval between the insertion of SEMS and laparoscopic surgery, and postoperative data. RESULTS: The tumors were situated in the recto-sigma (1 case), sigma (3 cases) and descending colon (3 cases). Immediate relief of the obstruction was achieved in all cases after SEMS insertion of the stent, and oral diet was started at 24 h. The 7 patients were operated on an average of 8 days (range 6-14) after insertion of the stent. Conversion to open surgery was necessary in one case for reasons not related to the stent. CONCLUSIONS: Preliminary results of the combination of SEMS and elective laparoscopic surgery demonstrate that the procedure is feasible and that it presents all the clinical advantages of a minimally invasive approach. The procedure is a valid alternative to traditional major urgent surgery.

Aged↗

Laparoscopic surgery in situs inversus: a literature review and a report of laparoscopic sigmoidectomy for diverticulitis in situs inversus.

BACKGROUND: Situs inversus (SI) is a rare autosomal recessive congenital defect in which the position of abdominal and/or thoracic organs is a "mirror image" of the normal one, in the sagittal plain. In 25% of these cases, SI is part of the Kartagener syndrome, together with bronchiectasis and chronic sinusitis. METHODS: We present a case of a patient with Kartagener syndrome and complete SI that was laparoscopically operated on for diverticulitis. We also review the published English information available on this rare condition. RESULTS: A review of the literature revealed another single case of laparoscopic sigmoidectomy and 27 cases of other laparoscopic interventions in the presence of SI. Those laparoscopic procedures included basic procedures such as explorations and cholecystectomies, as well as advanced procedures such as gastrectomy and gastric bypass. CONCLUSION: The laparoscopic approach is feasible in cases of SI, although technically more complicated because of the different position of the organs and the different laparoscopic view of the anatomy.

Adult↗

Mesh in the hiatus: a controversial issue.

OBJECTIVE: To analyze the experience acquired to date on the use of prosthetic mesh to prevent recurrence after laparoscopic repair of paraesophageal hernia. DATA SOURCES: Current English-language literature review. STUDY SELECTION: Case reports, series, and opinion articles on the use of mesh for paraesophageal hernia repair. DATA EXTRACTION AND SYNTHESIS: Study type and results were analyzed. Most articles were short case series. Few comparative or randomized trials assessing the procedure have been published to date. The information available showed that the use of a mesh for hiatal repair was safe and prevented recurrence. However, data on the long-term results were lacking, and infrequent but severe complications may arise. CONCLUSIONS: The mesh should be used selectively, and the decision to proceed should be based on clinical experience. In light of the evidence available, however, it appears to be safe, and the fears expressed in the past have not been confirmed.

Hernia, Hiatal↗

The massive hiatal hernia: dealing with the defect.

The success of laparoscopic fundoplication has extended the use of the laparoscopic approach to treating more difficult situations such as paraesophageal hernias (PEHs) or type III (mixed) hiatal hernia. The results have shown that laparoscopic repair is feasible and safe. However, several series have shown recurrence rates of up to 42% as a result of difficulty in the closure of the hiatal gap. Some authors recommend the use of prosthetic mesh to reinforce the hiatal closure. This review analyses the different techniques proposed to prevent recurrence after laparoscopic repair of PEHs. The information currently available shows that the use of a mesh for hiatal repair is safe and prevents recurrence. However, data on the long-term results are lacking, and infrequent but severe complications may arise. The mesh should be used selectively, and the decision to proceed should be based on clinical experience.

Fundoplication↗

Is the laparoscopic approach reasonable in cases of splenomegaly?

Laparoscopic splenectomy in cases of splenomegaly has been shown to be feasible in experienced hands, even though the size of the spleen increases the operative time and difficulty. Laparoscopic splenectomy for splenomegaly offers the same advantages as for patients with smaller spleens: a shorter hospital stay and a faster recovery. Recent experience has shown that hand-assisted laparoscopic surgery makes the surgical maneuvers during laparoscopic splenectomy in cases of splenomegaly considerably easier while preserving the advantages of a purely laparoscopic approach. This technique may facilitate and broaden the application of laparoscopy for splenectomy in patients with enlarged spleens.

Humans↗

Hand-assisted laparoscopic surgery.

HYPOTHESIS: Hand-assisted laparoscopic surgery (HALS) has been proposed as a useful alternative to conventional open or laparoscopic surgery. However, most information is fragmented and comes from specific or selective indications. To assess the current situation of HALS, a general overview of the fields of application, results, and quality of the evidence of these results is necessary. DATA SOURCES: Current English-language literature review. STUDY SELECTION: Case reports, series, and opinion articles on HALS. DATA EXTRACTION AND SYNTHESIS: Evaluation of the type of study and results. Most of the articles are short case series. Only a few comparative or randomized comparative trials on HALS for splenectomy and colectomy have been published. CONCLUSIONS: Hand-assisted laparoscopic surgery seems to be a promising technique that has been applied with success in a wide range of digestive tract-related surgical procedures. The main role is to help in difficult cases before conversion is necessary or for training unskilled surgeons, and not as an alternative to pure laparoscopic surgery. However, not enough evidence-based data are available to know exactly the final outcome of this technique in general surgery. Prospective randomized trials with established open or laparoscopic procedures are lacking, and these trials are needed to support the final role of HALS.

Colectomy↗

Laparoscopic treatment for intussusception of the small intestine in the adult.

The term intussusception refers to a spontaneous invagination of a portion of the intestine into another bowel loop. Its incidence is higher in children, but in adults it causes 1% to 5% of intestinal obstructions. The diagnosis of intussusception in the adult is difficult due to the variability of the symptoms. The condition may be chronic, intermittent, or acute. Surgical intervention is necessary in all cases and in up to 90% of cases an organic lesion inside the invaginated part of the bowel is found to be the lead point. The laparoscopic approach offers both a diagnostic and therapeutic option. Laparoscopy may be used as the final diagnostic or therapeutic tool for intussusception in the adult.

Aged↗

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.

Animals↗

Heterotopic implantation alters the regulation of apoptosis and the cell cycle and generates a new metastatic site in a human pancreatic tumor xenograft model.

Differences in growth and in response to antineoplastic drugs between s.c. and orthotopically implanted tumors in nude mice and between the primary tumor and the metastases in human tumors suggest that implantation site may alter the molecular regulation of tumor cells. We assessed the influence of implantation site on cell cycle and apoptotic regulation and the possible contribution of the implantation site in directing the choice of metastatic site by comparing the behavior of tumor aliquots of two human pancreatic xenografts (NP18 and NP9) implanted in the organ where the tumor grows (orthotopically), in heterotopic sites (the site of metastases (liver), and in nonmetastatic sites (subcutis and colon). We observed that implantation site changes tumor growth by altering apoptotic or cell cycle regulation in a tumor-specific manner. In the NP18 tumor it occurs by altering apoptotic induction and activation of the Bad/Bcl-XL/caspase-3 pathway through AKT and Erk regulation, but in the NP9 tumor by changing the activation and/or expression of the proteins that regulate the cell cycle (Erk, PCNA, and cyclin B1). We also observed that implantation site alters the metastatic pattern of the NP9 tumor, originating a new metastatic site.

Animals↗

Decrease in specific micronutrient intake in colorectal cancer patients with tumors presenting Ki-ras mutation.

BACKGROUND: The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and mutations, such as Ki-ras mutations, in genes implicated in the pathogenesis of these neoplasms. PATIENTS AND METHODS: The study was based on 246 cases and 296 controls. For the molecular study only 117 patients with Ki-ras tumor expression were included. Dietary patterns were assessed using a semi-quantitative food frequency questionnaire. RESULTS: Patients with Ki-ras mutations in codon 12 (K12) consumed significantly less vitamin A (p=0.02), B1 (p=0.01), D (p=0.02) and iron (p=0.03) than controls, whereas patients without these mutations had similar intakes of these nutrients to controls. The consumption of fiber, folate, vitamin E and potassium was lower in the two subgroups of patients (K12-positive or -negative) than in controls. Mutation in codon 13 was not associated with any nutrient deficit. CONCLUSION: These results support previous findings that certain micronutrients protect against colorectal neoplasia and emphasize the importance of considering the different molecular forms of CRC as etiologically distinct diseases.

Aged↗