Sulfasalazine in Prevention of Pouchitis After Proctocolectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for refractory ulcerative colitis. A non-standardized preventative treatment exists. Sulfasalazine has proved effective in acute pouchitis therapy. AIMS: The aim of this study was to retrospectively evaluate the effect of sulfasalazine in primary prophylaxis of pouchitis after proctocolectomy with ileal pouch-anal anastomosis. METHODS: Data files of patients who underwent total proctocolectomy with ileal pouch-anal anastomosis for refractory ulcerative colitis and/or dysplasia from January 2007 to December 2014, with a follow-up until August 2015, were analyzed. After closure of loop ileostomy, on a voluntary basis, patients received a primary prophylaxis of pouchitis with sulfasalazine (2000 mg per day) continually until acute pouchitis flare and/or drop out due to side effects. RESULTS: Follow-up data were available for 51 of the 55 surgical patients. Median follow-up time was 68 months (range 10-104). Thirty postoperative complications occurred in 25 patients. 45% of patients developed pouchitis. Sulfasalazine prophylaxis was administered in 39.2% of patients; 15% of the these developed pouchitis versus 64.5% (20/31) of the non-sulfasalazine patients (p < 0.001). Pouchitis-free survival curves were 90.55 months in sulfasalazine patients and 44.46 in non-sulfasalazine patients (log-rank test p = 0.001, Breslow p = 0.001). CONCLUSION: Sulfasalazine may be potentially administered in pouchitis prophylaxis after proctocolectomy with ileal pouch-anal anastomosis, but large prospectively controlled trials are needed.

A rare case of giant pseudopolyp and colitis cystica profunda coexistence in an ulcerative colitis patient / Un caso raro de coexistencia de un pseudopólipo gigante y colitis cística profunda en un paciente con colitis ulcerosa

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The challenge of education in colorectal cancer surgery: a comparison of early oncological results, morbidity, and mortality between residents and attending surgeons performing an open right colectomy.

OBJECTIVES: Ongoing education in surgical oncology is mandatory in a modern residency program. Achieving acceptable morbidity and mortality rates, together with oncological adequacy, is mandatory. The aim of the study was to compare early surgical outcomes in 2 groups of patients, those operated on by a surgical resident supervised by an attending surgeon and those operated on by 2 attending surgeons. DESIGN: Data from consecutive patients with right colon cancer undergoing a right hemicolectomy were collected and analyzed. The patients were divided into 2 groups according to the surgeons' credentials: residents supervised by an attending surgeon and 2 attending surgeons. To evaluate the specific case mix of the 2 groups, the Portsmouth-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (P-POSSUM) was calculated. Observed over expected 30-day morbidity and mortality rates were compared for the 2 groups. The number of lymph nodes retrieved was chosen to determine oncological appropriateness. Duration of the procedures was also recorded. RESULTS: From January 2008 to January 2012, 139 patients underwent an right hemicolectomy (76 resections performed by surgical residents and 63 by attending surgeons). Patient characteristics according to the P-POSSUM score and cancer stage were equivalent in the 2 groups. Observed over expected mortality and morbidity rates according to P-POSSUM were 0%/3.5% and 21.6%/40.5%, respectively, for the resident group (p = nonsignificant, p = 0.01) and 4.7%/5.8% and 25.4%/42.9%, respectively, for the attending surgeons (p = nonsignificant). The node count was 23.6 nodes for residents and 23.1 for the attending surgeons. The length of surgery was 159.9 minutes vs 159.4 minutes for residents and attending surgeons, respectively. CONCLUSIONS: Surgical oncology training of residents by expert surgeons cannot put patient's safety at risk. Our study showed that oncological accuracy and the 30-day complication rate were equivalent to the standard of care in both groups. Duration of the procedure was not affected by the presence of a trainee.

Small bowel obstruction caused by a large B-cell lymphoma in a patient with multicentric Castleman's disease: An unusual occurrence.

Multicentric Castleman's disease is a rare condition of systemic nonclonal lymph node hyperplasia. Because of its strong association with human herpes virus 8 (HHV8), the multicentric, more aggressive, form may progress to Kaposi sarcoma or non-Hodgkin lymphoma. While surgery is curative in the treatment of localized Castleman's disease, operative treatment of the diffuse form has as yet been unsatisfactory. We report the case of a patient presenting with postprandial vomiting of 1 month duration consistent with partial small bowel obstruction secondary to terminal ileum intussusception. Resection of the small bowel showed a stenosing tumor triggering the intussusception. On pathological examination, the tumor was found to be composed of HHV8-positive plasmablastic lymphoma cells. To our knowledge, this represents the first case of a complication due to the progression of multicentric Castleman's disease requiring surgical intervention for intussusception.

Can POSSUM accurately predict post-operative complications risk in patients with abdominal Crohn's disease?

BACKGROUND: Although the majority of patients with Crohn's disease (CD) are young, they are often seriously ill when surgery is required. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a risk prediction scoring system estimating 30-day complications. The primary endpoint was to evaluate POSSUM efficacy in this subgroup. The secondary endpoint was to determine any potential correlation between POSSUM, Harvey-Bradshaw Index (HBI), length of stay (LOS) and anastomotic leak. METHODS: All patients affected by abdominal CD who underwent elective and emergency surgery from 2006 to 2011 were prospectively enrolled in the study. POSSUM expected morbidity and mortality were compared to the observed outcomes (O/E ratio). Logistic regression analysis was performed to evaluate POSSUM and HBI adequacy. Correlation between POSSUM, HBI, LOS and anastomotic leak was investigated with linear regression analysis. RESULTS: One hundred twenty-three patients underwent abdominal surgery. The overall 30-day mortality rate estimated by the Portsmouth-POSSUM was 1.22% (95% confidence interval (CI) 0.4-3.6) while no deaths were observed (O/E = 0). The prediction regarding the post-operative complication rate was 22.04% (95% CI 11.1-51.2) and the observed overall morbidity rate was 21.95% (O/E = 0.99). The mean HBI score was 6.85 while LOS was 9.4 days. POSSUM and HBI were found to be significant predictors of post-operative complications at the univariate logistic regression analysis (OR 1.17 95% CI 1.06-1.30 and OR 1.25 95% CI 1.04-1.49, respectively). Linear regression analysis showed a significant correlation between POSSUM, HBI and LOS. CONCLUSION: POSSUM is precise in predicting post-operative complications in patients with abdominal CD. POSSUM correlates with HBI.

A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk.

The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case-control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.

Effectiveness of sentinel lymph node intraoperative examination in 753 women with breast cancer: are we overtreating patients?

OBJECTIVE: The goal of our study was to evaluate the sensitivity and specificity of sentinel lymph node biopsy (SLNB) frozen section (FS) examinations to detect metastatic lymph nodes and also its potential role in avoiding unnecessary demolitive axillary surgery. BACKGROUND: SLNB is the standard of care in surgical oncology of the breast. Intraoperative evaluation of the SLN seems to achieve sufficient sensitivity for macrometastasis (Ma), leading to axillary lymph node dissection (ALND) only when strictly necessary. Is it equally as clear when to perform ALND if micrometastasis (Mi) or isolated tumor cells (ITCs) are detected? METHODS: All consecutive patients from January 2005 to September 2010 operated on for breast cancer were prospectively enrolled. All patients underwent an FS SLNB. The sensitivity and specificity of SLN FSs in detecting Ma, Mi, and ITCs was calculated. All patients with Ma or Mi at FS underwent ALND. For all patients who underwent ALND, the number of metastatic non-SLNs was recorded and correlated to the size of the SLN metastasis. RESULTS: A total of 753 patients were enrolled. FS examination had an overall 54% sensitivity and 100% specificity in detecting metastatic disease (Ma/Mi/ITCs). The sensitivity rises to 89% if only Mas were considered and to 64% if Mas and Mis were counted together. All patients with Mas or Mis detected at FS had a completion ALND during the same procedure (156/222). All patients with Mas detected at final pathology (16 false negatives, 2.6%) and 50 women with Mis or ITCs (119 false negatives, 20%) underwent a delayed ALND. When Mis or ITCs were detected in the SLN, only 8 of 73 (10.9%) and none of 4 (0%) patients, respectively, had at least 1 metastatic non-SLN after ALND. Two patients (2/460, 0.43%) who had negative SLNs showed local axillary recurrence. After a mean follow-up of 32 months, none of the 71 patients with Mis or ITCs who did not undergo a second operation showed local recurrence. CONCLUSIONS: SLNB FS is highly effective in detecting the subgroup of patients who may benefit from completion ALND during the same surgical procedure. The role of Mi/ITCs in the SLN(s) is still unclear, but our data lean toward a less aggressive surgical approach.

Fecal detection of Mycobacterium avium paratuberculosis using the IS900 DNA sequence in Crohn's disease and ulcerative colitis patients and healthy subjects.

BACKGROUND AND AIM: Despite the increasing evidence of MAP/DNA isolation in Crohn's disease (CD), its potential pathogenetic role remains unclear. To further clarify the possible relationship between MAP and CD, we investigated the presence of IS900 DNA fragment in feces from Crohn's disease and ulcerative colitis (UC) patients and from healthy controls (HC). METHODS: Stool samples were collected from 31 CD, 20 UC, and 23 HC and stored at -20°C in 200-mg aliquots. DNA was extracted. MAP presence was detected with a specific PCR amplifying a 409-bp fragment from IS900. The specificity of PCR for IS900 was confirmed sequencing three positive products. Statistical analysis was performed using the Chi-square test. RESULTS: Twenty-one of 31 CD (68%), 13 of 20 UC (65%) and 11 of 23 HC (48%) were MAP-positive (CD vs. HC: p = ns; UC vs. HC: p = ns). With the limits of a small sample size, the IS900-positive percentage in CD and UC was higher than HC, although the difference was not statistically significant. CONCLUSIONS: The possibility to track the MAP presence in human feces represents a new approach to the "MAP hypothesis". Detection of MAP DNA in feces is very common, reaching very high prevalence both in CD and in UC and even in HC. Our findings seem consistent with a high prevalence of MAP asymptomatic infection among the general population and so the possible involvement of MAP in CD pathogenesis could be linked to a specific immune defective response.

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes.

Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.

Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The present work aimed at identifying a set of specific mRNAs expressed in colon tissue but not in blood cells. These mRNAs may represent useful markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay, following RNA extraction from peripheral blood samples. Using a data-mining tool called cDNA digital gene expression displayer (DGED), based on serial analysis of gene expression (SAGE) from the Cancer Genome Anatomy Project (CGAP) database, 4-colon and 14-blood cDNA libraries were analyzed. We selected 7 genes expressed in colon tissue but not in blood and were able to test 6 of them by RT-PCR in peripheral blood of CRC patients and healthy controls. We present a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as candidate markers of malignancy in blood samples of patients with colon cancer. SAGE DGED provided a list of the best candidate mRNAs predicted to detect colon cells in the blood, namely those encoding the following proteins: hypothetical protein LOC644844 (LOC644844, whose cDNA was not amplifiable), fatty acid binding protein 1 (FABP1), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), mucin 13 cell surface associated (MUC13), guanylate cyclase activator 2A (GUCA2A), amiloride binding protein 1 (ABP1), galactoside-binding, solute carrier family 26, member 3 (SLC26A3). The mRNA expression of these genes was evaluated in 8 samples from subjects diagnosed with CRC and 9 from healthy controls. We observed the expression of 2 of the 6 investigated genes in the blood samples of the vast majority of patients considered, but also in a subset of the controls. Our data confirm the extreme sensitivity of RT-PCR, making this technique able to detect minimal amounts of mRNA expressed in a non-tissue-specific manner. Moreover, DGED remains a powerful tool to identify candidate epithelial markers in blood, such as colon related mRNAs. However, to date, none of these qualified as tumour markers.

A preliminary audit experience of surgery for rectal cancer after neoadjuvant chemoradiation therapy.

AIMS AND BACKGROUND: A surgical audit is a systematic critical analysis of surgical performance, with the goal to improve the quality of patient care. Rectal cancer surgery is one of the most delicate procedures in the field of surgical oncology, with significant variations in terms of complications from center to center. Neoadjuvant chemoradiation therapy leads to a significant reduction in local recurrences in patients with locally advanced lower and medium rectal cancer. The aim of the study was to evaluate the influence of neoadjuvant chemoradiation therapy on postoperative morbidity and mortality in patients with rectal cancer. METHODS AND STUDY DESIGN: From January 1, 2003, to December 31, 2007, patients who underwent elective surgical resection for lower and medium rectal cancer in our Surgical Unit were prospectively analyzed. Patients (n=42) were divided into two groups: (1) those treated with neoadjuvant chemotherapy and consequent surgical resection (19/42); (2) those treated with primary surgical treatment (23/42). P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity) and CR-POSSUM (ColoRectal-POSSUM) scores were calculated for each patient group. Thirty-day mortality and morbidity rates were prospectively collected in a comprehensive data base. Data were evaluated by comparing the predictions of the two scoring systems in both study groups with clinically observed mortality and morbidity rates. RESULTS: In group 1, no death was registered (0/19). The P-POSSUM and CR-POSSUM expected mortality was 2.43% and 4.52%, respectively (P > 0.05). In group 2, a single death was documented (1/23, 4.35%). The P-POSSUM and CR-POSSUM expected mortality was 2.1% and 4.94%, respectively. The postoperative complications rate for group 1 was 10.52% (2/19) compared to 34.88% as expected from the P-POSSUM score (P < 0.05). In group 2, a postoperative complication rate of 39.13% (9/23) was observed compared to 34.26% as expected from the P-POSSUM score (P > 0.05). CONCLUSIONS: No significant influence on morbidity or mortality was detected in patients who underwent neoadjuvant radio-chemotherapy.

The EGFR R521K polymorphism influences the risk to develop colorectal cancer.

Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.

An easy-to-use solution for clinical audit in colorectal cancer surgery.

BACKGROUND: Clinical audit has been increasingly required for the accreditation process in every modern healthcare system. Data collection and analysis are excessively time-consuming in everyday practice. The primary aim of our study was to evaluate the effectiveness of an innovative database to assist surgeons in monitoring clinical practice outcomes in colorectal cancer surgery. The second purpose was to compare observed mortality rates to 3 risk-predicting operative scoring systems. METHODS: Data were evaluated from 208 consecutive patients undergoing elective and emergency surgery for colorectal cancer over a 2-year period (2003-2004). A new database was developed with specific queries to compare the observed and the expected mortality rates according to 3 scoring systems: the Portsmouth-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (P-POSSUM), the ColoRectal-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (CR-POSSUM), and the Association of ColoProctology or Great Britain & Ireland (ACPGBI) score. Results were discussed at regular intervals. Surgeons' satisfaction with each system was evaluated with a questionnaire. RESULTS: The observed mortality rate was 6.25%, which was significantly lower than the values predicted by CR-POSSUM and ACPGBI colorectal scores (9.14% and 19.42%, respectively; P < .05). P-POSSUM was the most accurate predictor of mortality, with a value of 7.93%. A total of 80% of the surgical staff considered this type of surgical audit activity as clinically useful. CONCLUSION: The study confirms the usefulness of a dedicated database in a surgical audit activity. The ACPGBI colorectal score largely overestimated 30-day mortality in our experience.

Diffuse cavernous haemangioma of the rectum and anus: an unusual case of rectal bleeding with challenging management.

Diffuse cavernous haemangioma of the rectum (DCHR) is an uncommon vascular pathology usually diagnosed in younger patients (5-25 years old) with painless, recurrent rectal bleeding. Here, an unusual case of an older patient with sigmoid adenocarcinoma and concomitant diffuse DCHR from the rectum to the distal edge of the anal canal is reported.The purpose of this article is to report this unusual case and to discuss pitfalls in diagnosis, preoperative assessment and treatment of DCHR.

Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines.

BACKGROUND: EGFR is frequently overexpressed in colon cancer. We characterized HT-29 and Caco-2, human colon cancer cell lines, untreated and treated with cetuximab or gefitinib alone and in combination with EGF. METHODS: Cell growth was determined using a variation on the MTT assay. Cell-cycle analysis was conducted by flow cytometry. Immunohistochemistry was performed to evaluate EGFR expression and scanning electron microscopy (SEM) evidenced the ultrastructural morphology. Gene expression profiling was performed using hybridization of the microarray Ocimum Pan Human 40 K array A. RESULTS: Caco-2 and HT-29 were respectively 66.25 and 59.24 % in G0/G1. They maintained this level of cell cycle distribution after treatment, suggesting a predominantly differentiated state. Treatment of Caco-2 with EGF or the two EGFR inhibitors produced a significant reduction in their viability. SEM clearly showed morphological cellular transformations in the direction of cellular death in both cell lines treated with EGFR inhibitors. HT-29 and Caco-2 displayed an important reduction of the microvilli (which also lose their erect position in Caco-2), possibly invalidating microvilli absorption function. HT-29 treated with cetuximab lost their boundary contacts and showed filipodi; when treated with gefitinib, they showed some vesicles: generally membrane reshaping is evident. Both cell lines showed a similar behavior in terms of on/off switched genes upon treatment with cetuximab. The gefitinib global gene expression pattern was different for the 2 cell lines; gefitinib treatment induced more changes, but directly correlated with EGF treatment. In cetuximab or gefitinib plus EGF treatments there was possible summation of the morphological effects: cells seemed more weakly affected by the transformation towards apoptosis. The genes appeared to be less stimulated than for single drug cases. CONCLUSION: This is the first study to have systematically investigated the effect of cetuximab or gefitinib, alone and in combination with EGF, on human colon cancer cell lines. The EGFR inhibitors have a weaker effect in the presence of EGF that binds EGFR. Cetuximab treatment showed an expression pattern that inversely correlates with EGF treatment. We found interesting cyto-morphological features closely relating to gene expression profile. Both drugs have an effect on differentiation towards cellular death.

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer.

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted.

Search for epithelial-specific mRNAs in peripheral blood of patients with colon cancer by RT-PCR.

Research has widely supported the efficacy of screening for colorectal cancer in reducing mortality. A blood-based assay potentially represents a more accessible early detection tool for the identification of solid tumor cells originating from a primary tumor site in the body. We demonstrate a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as markers of malignancy in blood samples of patients with colon cancer. The present study aims to identify a set of specific mRNAs expressed in epithelial cells but not in blood cells, which may be useful as markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay following semi-automated RNA extraction from peripheral blood samples. Our approach includes a systematic search for candidate markers using digital differential display, search on UniGene colon EST libraries and analysis of published data on colon cancer gene expression. A final list included the following genes: bone morphogenetic protein 4 (BMP4), cyclin D (CycD), family with sequence similarity 3, member D (FAM3D), gastrin (GAS), glycoprotein A33 transmembrane (GPA33), glutathione peroxidase 2 gastrointestinal (GPX2), galactoside-binding, soluble, 4 (galectin 4) (LGALS4), non-SMC, structural maintenance of chromosomes, element 1 protein (NSE1), tumor-associated calcium signal transducer 1 (TACSTD1), telomerase reverse transcriptase (hTERT), trefoil factor 3 intestinal (TFF3), transmembrane 4 superfamily member 3 (TM4SF3), UDP glycosyltransferase 1 family, polypeptide A9 (UGT1A9), villin 1 (VIL1), and the novel gene FLJ20127. The mRNA expression of these genes was evaluated in a pool of 16 samples from subjects diagnosed with colon cancer and from 16 normal-controls. We observed expression in 13 of the 15 investigated genes from the blood samples of the vast majority of patients considered, but also in a certain percentage of the controls (from 14.3 to 100%). This finding confirms that the extreme sensitivity of RT-PCR is able to detect minimal amounts of mRNA expressed in a non tissue-specific manner ('illegitimate transcription'). On the contrary, NSE1 and GAS mRNAs were not detected either in patient or in control blood samples; however, they were abundantly expressed in normal and cancerous colon mucosa, encouraging further search for useful markers able to detect epithelial cells in peripheral blood.

Cirugía conservadora de los esfínteres para el cáncer de recto bajo / Conservative surgery of the sphincters for low rectal neoplasms

Se revisaron en forma retrospectiva las historias clínicas de 43 pacientes que fueron operados por cáncer de recto situados a menos de 12 cm de la margen anal, en el Servicio de Cirugía Ganeral del Hospital Militar "Dr. Carlos Arvelo" durante el período comprendido entre 1969 y 1988. 21 pacientes (49%) eran del sexo masculino y 22 (51%) femeninos con un promedio de edad de 61 años. En 22 (51%) se practicó cirugía conservadora: 18 resecciones anteriores bajas, 3 anastomosis coloanales y un pull-through, en 21 pacientes (49%) resección abdominoperineal. Todos histológicamente correspondieron a adenocarcinomas excepto un cloacogénico. Se presentaron 2 (9%) muertes operatorias en la cirugía conservadora y 7 (33%) en la no conservadora. De 43 pacientes 34 sobrevivieron el procedimiento quirúrgico, de los sometidos a resección conservadora 4 (20%) mueren sin recurrencia y 2 (10%) con recurrencia. De los casos intervenidos con resección abdominoperineal 1 (7%) murió sin recurrencia y 4 (29%) con recurrencia. Se realiza una evaluación crítica de nuestra experiencia y la publicada en la literatura internacional, sobre la cirugía conservadora del esfínter en el cáncer de recto bajo