PAK and PI3K pathway activation confers resistance to KRASG12C inhibitor sotorasib.

BACKGROUND: KRAS is a frequently mutated oncogene in human cancer. Clinical studies on the covalent inhibitors of the KRASG12C mutant have reported promising results. However, primary and acquired resistance may limit their clinical use. METHODS: Sotorasib-resistant cell lines were established. We explored the signalling pathways activated in these resistant cell lines and their roles in sotorasib resistance. RESULTS: The resistant cells exhibited increased cell-matrix adhesion with increased levels of stress fibres and focal adherens. p21-activated kinases (PAKs) were activated in resistant cells, which phosphorylate MEK at serine 298 of MEK and serine 338 of c-Raf to activate the mitogen-activated protein kinase pathway. The PAK inhibitors FRAX597 and FRAX486 in synergy with sotorasib reduced the viability of KRASG12C mutant cancer cells. Furthermore, the PI3K/AKT pathway was constitutively active in sotorasib-resistant cells. The overexpression of constitutively activated PI3K or the knockdown of PTEN resulted in resistance to sotorasib. PI3K inhibitor alpelisib was synergistic with sotorasib in compromising the viability of KRASG12C mutant cancer cells. Moreover, PI3K and PAK pathways formed a mutual positive regulatory loop that mediated sotorasib resistance. CONCLUSIONS: Our results indicate that the cell-matrix interaction-dependent activation of PAK mediates resistance to sotorasib through the activation of MAPK and PI3K pathways.

Safety and Efficacy of Oral Nalbuphine on Postoperative Pain in Hemorrhoidectomy Patients: A Randomized, Double-blind, Placebo-controlled, Pivotal Trial.

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20% to 40% of hemorrhoidectomy patients. Compared with morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from the intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale pain intensity scores. RESULTS: Visual Analog Scale results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P =0.0301). According to Brief Pain Inventory Short-Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group ( P <0.0001). Drug-related adverse events were mild-to-moderate and resolved by the treatment end. No drug-related severe adverse events were observed. DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe post hemorrhoidectomy pain and may provide another option for patients to control their pain.

A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America.

Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMICs) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included the use of Escherichia coli asparaginase,6-mercaptopurine instead of thioguanine and the use of rituximab among patients with CD20+. A total of 95 patients with a median age of 23 (range, 14-49) years treated with this modified scheme were prospectively assessed at 5 centers in Mexico and 1 in Guatemala. Among these, 87.8% achieved a complete response after induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.81-10.10) and postinduction minimal residual disease (HR, 4.67; 95% CI, 1.75-12.44). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation, respectively), and the treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.

Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer. METHODS: We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis. RESULTS: CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P = 0.025) and survival of patients with colorectal cancer (P = 0.002), and correlated inversely with tumor regression grading (P = 0.021) after CCRT in patients with rectal cancer. CONCLUSIONS: The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.

Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit.

The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival (p = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.

Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer.

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.

Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.

PURPOSE: The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS: Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS: We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION: These results highlight the collateral damage of COVID-19 in oncology patients.

Necrotizing fasciitis due to acute perforated appendicitis: case report.

Acute appendicitis is one of the most common surgical emergencies. Accurate diagnosis is often hindered due to various presentations that differ from the typical signs of appendicitis, especially the position of the appendix. A delay in treatment increases the likelihood of complications such as perforation, which is associated with an increase in morbidity and mortality rates. We herein present the case of a 76-year-old woman presenting with necrotizing fasciitis of the abdominal wall and right flank regions due to a perforated appendix. Such complication is extremely rare but life-threatening. It may be confused with cellulitis, causing a delay in aggressive treatment. This case represents an unusual complication of a common disease. Also, acute appendicitis or intra-abdominal pathologies should be taken into consideration in determining the cause of necrotizing fasciitis presenting over abdominal, flank, or perineal regions.

Determining the risk factors associated with the development of Clostridium difficile infection in patients with hematological diseases.

BACKGROUND: Clostridium difficile infection (CDI) is a nosocomial condition prevalent in patients with hematological disorders. We aimed to identify the risk factors associated with the development of CDI and assess the mortality rate at 15 and 30 days among hematologic patients admitted to a tertiary care center. METHODS: We conducted a retrospective case-control study from January 2010 to December 2015. Forty-two patients with hematologic malignancy and CDI, and 84 with hematologic disease and without history of CDI were included in the case and control groups, respectively. RESULTS: Univariate analysis revealed that episodes of febrile eutropenia [odds ratio (OR), 5.5; 95% confidence interval (CI), 2.3-12.9; P<0.001], admission to intensive care unit (OR, 3.8; 95% CI, 1.4-10.2; P=0.009), gastrointestinal surgery (OR, 1.2; 95% CI, 1.1-1.4; P<0.001), use of therapeutic (OR, 6.4; 95% CI, 2.5-15.9; P<0.001) and prophylactic antibiotics (OR, 4.2; 95% CI, 1.6-10.7; P=0.003) in the last 3 months, and >1 hospitalization (OR, 5.6; 95% CI, 2.5-12.6; P<0.001) were significant risk factors. Multivariate analysis showed that use of therapeutic antibiotics in the last 3 months (OR, 6.3; 95% CI, 2.1-18.8; P=0.001) and >1 hospitalization (OR, 4.3; 95% CI, 1.7-11.0; P=0.002) were independent risk factors. Three (7.1%) and 6 (14.2%) case patients died at 15 and 30 days, respectively. CONCLUSION: The risk factors for developing CDI were exposure to therapeutic antibiotics and previous hospitalization. Hematological patients who developed CDI had higher early mortality rates, suggesting that new approaches for prevention and treatment are needed.

Exposure to nicotine-derived nitrosamine ketone and arecoline synergistically facilitates tumor aggressiveness via overexpression of epidermal growth factor receptor and its downstream signaling in head and neck squamous cell carcinoma.

Long-term nicotine-derived nitrosamine ketone (NNK) and arecoline exposure promotes carcinogenesis and head and neck squamous cell carcinoma (HNSCC) progression, although most associated data on the two were analyzed individually. The molecular mechanisms underlying tumor progression associated with the synergistic effects of NNK and arecoline remain unclear. We treated SCC-25 and FaDu cells with NNK and arecoline (separately or in combination) for 3 months. Comparative analysis was performed to investigate the mechanism underlying the acquisition of properties related to tumor promotion, including stemness, anti-apoptosis, and resistance to HNSCC therapeutics. Long-term exposure to NNK and arecoline resulted in an increase in cancer stem cell properties, anti-apoptosis, and the resistance to cisplatin in HNSCC. We detected abundant epidermal growth factor receptor (EGFR) expression in HNSCC cells after combined treatment with NNK and arecoline. EGFR was pivotal in inducing tumor promotion and anti-apoptosis in cancer cells by inducing pAKT and NFκB. Combined treatment with NNK and arecoline synergistically facilitated tumor aggressiveness via EGFR-AKT signaling. Targeting EGFR-AKT signaling may be a feasible strategy for treating HNSCC.

Heterotopic mesenteric ossification after total colectomy for bleeding diverticulosis of the colon--a rare case report.

Heterotopic bone formation within an abdominal incision is a rare sequela of abdominal surgery. Only a few previous reports have noted heterotopic ossification in the mesentery of the small intestine and peri-ileostomy. Here, we report the case of a 60-year-old man who underwent emergent laparotomy and total colectomy with end ileostomy and developed this condition 1 month postoperatively. Heterotopic ossification in the peri-ileostomy tissue caused stenosis of the ileostoma. Laparotomy for re-anastomosis due to a large bone formation at an abdominal midline scar is very difficult and results in a massive abdominal wall defect. Therefore, we used a lower transverse incision to avoid the site of bone formation and resected the terminal ileum with its ossified mesentery. Then, we successfully carried out an anastomosis between the ileum and the rectum. The possible pathogenesis is a metaplastic mechanism of differentiation of immature multipotent mesenchymal cells. Our case provides the experience of treatment and new perspective on currently held hypotheses of heterotopic bone formation.

Increased chemoresistance via Snail-Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative.

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC.

The molecular and clinical verification of therapeutic resistance via the p38 MAPK-Hsp27 axis in lung cancer.

UNLABELLED: Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin-resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance-related genes. Gradual morphological alterations showing epithelial-to-mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival. SUMMARY: DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK-Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients.

The outcome of 5-fluorouracil chemotherapy after the completion of neoadjuvant chemoradiotherapy, administered until 2 weeks before rectal cancer resection.

BACKGROUND: In most institutions, locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy followed by surgery 6-8 weeks later, allowing time for tumor response and recovery from chemoradiotherapy-related toxicities. In our hospital, we continuously administer chemotherapy after the completion of chemoradiotherapy, until 2 weeks before surgery for most patients. METHODS: This was a retrospective study. Patients received a diagnosis of adenocarcinoma of the rectum at our hospital between January 2003 and December 2008 and received neoadjuvant chemoradiotherapy and curative surgery. Chemoradiotherapy consisted of continuous infusion of 225 mg/m(2) 5-fluorouracil, 5 days per week. Radiation therapy was delivered at 1.8 Gy per day, 5 days per week for 5-6 weeks (median radiation dose, 50.4 Gy). Chemotherapy was continued until 2 weeks before surgery, and surgery was performed 6-8 weeks after completion of chemoradiotherapy. RESULTS: The study included 119 patients (median age, 61 years; range, 24-84 years). Twenty-nine patients (24.4%) had a complete response and 65 (54.6%) had a partial response. Over a median follow-up duration of 52 months, 10 patients experienced local recurrence and 18 had distant metastasis. The 5-year overall and disease-free survival rates were 80.6% and 72.9%, respectively. Grade 3-4 toxicity only occurred in 14 patients (11.8%). CONCLUSION: Continued chemotherapy with 5-fluorouracil after completing neoadjuvant chemoradiotherapy until 2 weeks before surgery for locally advanced rectal cancer results in a good pathological control rate, with low toxicity. Patients who achieved a complete pathological response had a better long-term oncological outcome than those who did not.

Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.

BACKGROUND: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. METHODS: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. RESULTS: Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. CONCLUSION: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.

Prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 / Prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus

Resumen Introducción: La enfermedad cardiovascular es la causa principal de muerte en pacientes con diabetes mellitus. La prevalencia de cardiopatía isquémica asintomática es más alta en pacientes diabéticos que en no diabéticos y se asocia a peor pronóstico. Objetivo: Identificar la prevalencia de cardiopatía isquémica asintomática en pacientes con diabetes mellitus tipo 2 en un hospital de tercer nivel de atención de Guatemala y analizar la posible asociación de dicha enfermedad con características epidemiológicas, clínicas y metabólicas. Métodos: Estudio de corte transversal en el que se estudió una muestra de 92 pacientes diabéticos seleccionados de forma aleatoria simple. Se realizó electrocardiograma, que cuando fue negativo para isquemia ameritó prueba de esfuerzo, o de lo contrario, ecocardiograma de estrés con dobutamina. Resultados: La edad media de los participantes fue de 57 años, 88% de los cuales eran mujeres; la duración media de la diabetes fue 7 años. Se encontró cardiopatía isquémica asintomática en el 22,8% de los casos. No se hallaron posibles asociaciones entre cardiopatía isquémica asintomática y edad, sexo, enfermedad arterial periférica, índice de masa corporal, índice tobillo-brazo, hipertensión arterial, dislipidemia, tabaquismo activo, sedentarismo, sobrepeso/obesidad, alcoholismo, glucosa en ayunas, hemoglobina glicosilada, colesterol total, colesterol HDL, colesterol LDL, ácido úrico, creatinina, tasa de filtrado glomerular y microalbuminuria. Conclusiones: La prevalencia de cardiopatía isquémica asintomática en la población estudiada con diabetes mellitus tipo 2 fue de 22,8%. No se encontraron posibles asociaciones de cardiopatía isquémica asintomática con las variables estudiadas.

Abstract Introduction: Cardiovascular disease is the main cause of death in patients with diabetes mellitus. The prevalence of asymptomatic ischaemic heart disease is higher in diabetic patients than in non-diabetic ones, and is associated with a worse prognosis. Objective: To determine the prevalence of asymptomatic ischaemic heart disease in patients with type 2 diabetes mellitus in a third level of care hospital in Guatemala, as well as to analyse the possible relationship of this disease with epidemiological, clinical, and metabolic characteristics. Methods: A cross-sectional study was conducted on a sample of 92 randomly selected diabetic patients. An electrocardiogram was performed, which when it was negative for ischaemia, an exercise stress test or a dobutamine stress echocardiogram was performed. Results: The mean age of the participants was 57 years, 88% of whom were women. The mean duration of the diabetes was 7 years. Asymptomatic ischaemic heart disease was found in 22.8% of case. No significant associations were found between ischaemic heart disease and age, gender, peripheral arterial disease, body mass index, ankle-brachial index, arterial hypertension, dyslipidaemia, active smoking, sedentarism, overweight/obesity, alcoholism, fasting glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, creatinine, glomerular filtration rate, and urine microalbumin. Conclusions: The prevalence of asymptomatic ischaemic heart disease was 22.8% in the population studied with type 2 diabetes mellitus. No significant associations were found between ischaemic heart disease and the variables studied.

Hand-assisted laparoscopic total colectomy for slow transit constipation.

PURPOSE: Current medical treatments for slow transit constipation (STC) are often ineffective, and total colectomy with ileorectal anastomosis has been the procedure of choice for selected patients with refractory STC. Today, minimally invasive approaches are being utilized in a greater number of procedures as surgeons become more familiar with the techniques involved. The aim of this study was to assess the safety and utility of hand-assisted laparoscopic total colectomy for STC. METHOD: From January 2002 to December 2005, 44 women presented with complaints of intractable constipation and failed to respond to medical treatment. Slow transit constipation was diagnosed after a series of examinations, including a colonic transit test, anal manometry, balloon expulsion test, and barium enema. All eligible patients underwent a hand-assisted laparoscopic total colectomy with ileorectal anastomosis. Main outcome measures included the operative time, conversion to open procedure, blood loss, time to return of flatus, length of postoperative hospital stay, and complications. RESULT: The mean operative time was 197 min (range, 125-295 min). The mean estimated blood loss was 113 ml (range, 100-300 ml). The mean day of first time to flatus was 2 days, and the mean hospital stay was 7.6 days. There was no conversion to an open procedure and no surgical mortality. In the following period, two patients developed intestinal obstruction, which underwent exploratory laparotomy. However, some 39 patients (88.6%) expressed excellent or good in satisfaction. CONCLUSION: Hand-assisted laparoscopic total colectomy could be a safe and efficient technique in the treatment of STC.