Barriers to the use of tests for early detection of colorectal cancer in Chile.

This study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.

Colorectal cancer trends in Chile: A Latin-American country with marked socioeconomic inequities.

INTRODUCTION: Colorectal cancer (CRC) is the third most frequent malignant disease in the world. In some countries with established screening programs, its incidence and mortality have decreased, and survival has improved. AIMS: To obtain reliable data about the epidemiology of CRC in Chile, we analyzed the trends in the last ten years and the influence of observable factors on survival, including a nationwide health program for CRC treatment access (GES program). METHODS: Publicly available data published by the Ministry of Health and National Institute of Statistics were used. Data were obtained from registries of mortality and hospital discharges, making follow-up of the individuals possible. Crude and age-standardized incidence and mortality rates were calculated, and individual survival was studied by constructing Kaplan-Meier curves. Finally, a Cox statistical model was established to estimate the impact of the observable factors. RESULTS: We found 37,217 newly identified CRC patients between 2008 and 2019 in Chile, corresponding to 103,239 hospital discharges. In the same period, 24,217 people died of CRC. A nearly linear, steady increase in crude incidence, mortality and prevalence was observed. CRC incidence was the lowest in the North of the country, increasing toward the South and reaching a maximum value of 34.6/100,000 inhabitants/year in terms of crude incidence and 20.7/100,000 inhabitants/year in terms of crude mortality in the XII region in 2018. We found that older patients had lower survival rates, as well as men compared to women. Survival was significantly better for patients with private insurance than those under the public insurance system, and the treating hospital also played a significant role in the survival of patients. Patients in the capital region survived longer than those in almost every other part of the country. We found no significant effect on survival associated with the GES program. CONCLUSIONS: We found important inequalities in the survival probabilities for CRC patients in Chile. Survival depends mainly on the type of insurance, access to more complex hospitals, and geographical location; all three factors correlated with socioeconomic status of the population. Our work emphasized the need to create specific programs addressing primary causes to decrease the differences in CRC survival.

Consenso chileno de diagnóstico y manejo de neoplasias quísticas pancreáticas. Club de páncreas Chile-SCHGE / Chilean consensus on diagnosis and management of pancreatic cystic neoplasms

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Sarcomatoid carcinoma of the pancreas - a rare tumor with an uncommon presentation and course: A case report and review of literature.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) is a rare type of pancreatic neoplasm, and only a few cases have been described in the literature. Histologically, it is composed mostly of atypical spindle cells with apparent sarcomatous features. CASE SUMMARY: This is a report of a 61-year-old Chilean woman who underwent medical investigation for acute abdominal pain. Computed tomography identified a solid tumor in the tail of the pancreas with features suspicious of malignancy. En-bloc distal pancreatectomy and splenectomy were performed to excise the tumor. Histopathology and immunohistochemistry were confirmatory of sarcomatoid carcinoma with lymphovascular invasion. After surgery, the patient did not receive chemotherapy. Previous studies indicate a poor prognosis for this type of malignancy. However, our patient has survived for 35 mo with no recurrence to date. CONCLUSION: The case presented herein is a patient with an SCP with a rare presentation and long-term survival after surgery despite not receiving adjuvant chemotherapy.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori.

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

BACKGROUND: Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. RESULTS: A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41-5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63-2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80-3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40-21.33, p = 4.1 × 10- 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13-0.10, p = 0.03). CONCLUSIONS: NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

Polymorphisms PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in a high risk population.

Genetic variants are considered risk factors for gastric cancer. To date, 61 polymorphisms have been identified as associated with this disease. The aim of the present study was to analyze the association of some of those polymorphisms with GC in Chile. We performed a case-control study including 310 gastric cancer cases and 311 controls to assess the association of 36 single-nucleotide polymorphisms genotyped by Global Screening Array (GSA). Three polymorphisms was significantly associated: PSCA rs2294008 (allele model, OR = 1.49, 95%CI 1.17-1.88, P = 1.08 × 10-3), IL-4 rs2243250 (allele model, OR = 1.28, 95%CI 1.01-1.62, P = 0.04), and MUC1 rs4072037 (allele model, OR = 0.78, 95%CI 0.61-0.99, P = 0.04).PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in Chile. It suggests that those polymorphisms could be used as biomarkers to assess the genetic risk for this cancer outside of the previously studied populations, not only for East Asians and Caucasians populations.

[Variceal and non-variceal upper gastrointestinal bleeding. Analysis of 249 hospitalized patients]. / Hemorragia digestiva alta variceal y no variceal: mortalidad intrahospitalaria y características clínicas en un hospital universitario (2015-2017).

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is one of the main reasons of hospitalization due to gastrointestinal causes. Reported mortality rates range from 5 to 12%. AIM: To determine hospital mortality and associated risk factors in hospitalized patients with UGIB. To compare the clinical characteristics and outcomes of patients with variceal versus non-variceal UGIB. MATERIAL AND METHODS: Review of medical records of 249 patients (62% males) discharged with the diagnosis of UGIB at a clinical hospital between 2015 to 2017. Demographic and clinical characteristics and adverse clinical outcomes (surgery, length of hospital stay and in-hospital mortality) were recorded. A comparative analysis between patients with Variceal and Non-variceal UGIB was carried out. RESULTS: Seventy two percent of UGIB were non-variceal (peptic ulcer in 44%). Two patients required surgery (both died). Median of length of hospital stay was seven days (interquartile range (IQR) 4-13). Overall hospital mortality was 13 and 4% in variceal and non-variceal UGIB, respectively (p = 0.024). The variables associated with mortality were: red blood cell transfusion (odds ratio (OR): 18.7, p < 0.01), elevated creatinine on admission (OR: 3.30, p = 0.03) and variceal bleeding (OR: 3.23, p = 0.02). CONCLUSIONS: Hospital mortality of UGIB remains high, especially in variceal UGIB. Elevated creatinine levels on admission, the need of transfusion of red blood cells and variceal etiology are risk factors for mortality.

Association between autoimmune pancreatitis and ulcerative colitis: a report of 12 patients.

INTRODUCTION: pancreatic manifestations in inflammatory bowel disease (IBD) mainly include acute pancreatitis secondary to drugs and, less frequently, autoimmune pancreatitis, in particular type 2 autoimmune pancreatitis. METHODS: retrospective study of patients diagnosed with ulcerative colitis (UC) and autoimmune pancreatitis (AIP) in control at two centers in Santiago, Chile, between 2007 and 2018. Clinical data, laboratory results, images and response to treatment were recorded. RESULTS: twelve patients were identified with both diseases, the average age was 34 years and 42 % were male. In all cases, a likely diagnosis with type-2 AIP was established based on pancreatic magnetic resonance imaging (MRI), association with IBD and a rapid response to therapy with corticosteroids. Samples for histology were obtained from two patients, which showed inconclusive results. AIP recurrence was reported in only one case. A total of 58 % of patients had extensive UC, 100 % received 5-ASA therapy and 33 % were treated with azathioprine. Only one patient had a serious flare-up, none developed complications and none required biologics or surgery. CONCLUSION: an association between UC and type-2 AIP was confirmed in our cases. No increase in IBD severity was observed in this group of patients.

Hemorragia digestiva alta variceal y no variceal: mortalidad intrahospitalaria y características clínicas en un hospital universitario (2015-2017) / Variceal and non-variceal upper gastrointestinal bleeding. Analysis of 249 hospitalized patients

Background: Upper gastrointestinal bleeding (UGIB) is one of the main reasons of hospitalization due to gastrointestinal causes. Reported mortality rates range from 5 to 12%. Aim: To determine hospital mortality and associated risk factors in hospitalized patients with UGIB. To compare the clinical characteristics and outcomes of patients with variceal versus non-variceal UGIB. Material and Methods: Review of medical records of 249 patients (62% males) discharged with the diagnosis of UGIB at a clinical hospital between 2015 to 2017. Demographic and clinical characteristics and adverse clinical outcomes (surgery, length of hospital stay and in-hospital mortality) were recorded. A comparative analysis between patients with Variceal and Non-variceal UGIB was carried out. Results: Seventy two percent of UGIB were non-variceal (peptic ulcer in 44%). Two patients required surgery (both died). Median of length of hospital stay was seven days (interquartile range (IQR) 4-13). Overall hospital mortality was 13 and 4% in variceal and non-variceal UGIB, respectively (p = 0.024). The variables associated with mortality were: red blood cell transfusion (odds ratio (OR): 18.7, p < 0.01), elevated creatinine on admission (OR: 3.30, p = 0.03) and variceal bleeding (OR: 3.23, p = 0.02). Conclusions: Hospital mortality of UGIB remains high, especially in variceal UGIB. Elevated creatinine levels on admission, the need of transfusion of red blood cells and variceal etiology are risk factors for mortality.

Gastropatía hipertrófica por IgG4: reporte del primer caso en Chile / IgG4 related hypertrophic gastropathy: report of one case

IgG4 related disease is a systemic autoimmune disease, which can affect different organs. The most common digestive manifestation is autoimmune pancreatitis (AIP), followed by involvement of bile ducts and the major papilla. The stomach is only rarely involved. We report a 71-year-old diabetic woman consulting for jaundice and weight loss. Abdominal CAT scan, cholangio resonance imaging, endosonography and a serum IgG4 of five times the normal value, lead to the diagnosis of an autoimmune pancreatitis. An upper gastrointestinal endoscopy showed a diffuse thickening of gastric folds. The pathological study confirmed the presence of IgG4 positive plasma cells. The patient was successfully treated with steroids.

IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer Patients.

BACKGROUND/AIM: Inflammation is a key process in gastric carcinogenesis. Cytokines are mediators of inflammation and are involved in metastasis and tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in gastric cancer risk in Chile. In the present study, we aimed to analyze whether these polymorphisms are associated with overall survival (OS) in gastric cancer (GC) patients. PATIENTS AND METHODS: A total of 153 individuals with GC diagnosis were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox regression models using SNPs as predictor variables. The following SNPs were genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 -251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 -1082A>G); rs28372698 (IL32). RESULTS: Interleukin-8 rs4073 (IL-8 -251T>A) showed association with OS under the dominant model (TA + AA) only when adjusted by clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18), but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q-value=0.37). No significant differences were observed after adjusting for population stratification (PC1 and PC2 from Principal Component Analysis using genotypes from Infinium Global Screening Array). After stratification by clinicopathological variables, the association with shorter overall survival was higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97). CONCLUSION: These results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a prognostic marker of GC survival warrants further investigation.

[Helicobacter pylori infection detected during upper gastrointestinal endoscopy]. / Disminución en la frecuencia de infección por Helicobacter pylori en endoscopías digestivas altas.

BACKGROUND: Helicobacter pylori (HP) is the most widespread chronic human infection worldwide and the most important pathogenic factor of gastric cancer. The calculated prevalence at the Clinical Hospital of the University of Chile from 2002 to 2005 was 44.9%. AIM: To determine the current prevalence of HP in patients undergoing an upper gastrointestinal endoscopy (UGI) and analyze its distribution according to age and endoscopic findings. MATERIAL AND METHODS: We reviewed 3.433 UGI performed during the year 2015, selecting those in which rapid urease test (RUT) was done. A positive RUT or a positive gastric biopsy (GB) were considered as HP infection. RESULTS: RUT was done in 1862 UGI (55%) performed in patients aged 51 ± 17 years, (66% women). In 23% of these endoscopies, the RUT was positive. A GB was obtained 43% of endoscopies and 30% were positive for HP. In 105 patients the RUT was negative and the GB positive (rendering a 19.5% false negative rate). HP was detected by RUT and GB in 29% of endoscopies. The highest prevalence of infection (38.1%) was found between 40 and 49 years. HP infection had odds ratio of 4.24 for nodular gastropathy, 2.63 for gastric ulcer and 2.14 for duodenal ulcer (p < 0.05). CONCLUSIONS: HP prevalence in our center decreased significantly from 44.9% to 28.9% in 11 years. False negative RUT results may bias this finding. The use of proton pump inhibitors and antimicrobials that can interfere with the detection of HP should be registered to properly analyze the results of the RUT.

Polymorphisms in TWIST1 and ZEB1 Are Associated with Prognosis of Gastric Cancer Patients.

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) program has been linked as a driver of metastatic dissemination by conferring migratory and invasive capacity to cancer cells. Gastric cancer (GC) patients with tumors expressing altered levels of EMT markers have low survival. This study aimed to assess if polymorphisms of CDH1, TWIST1, SNAIL2, ZEB1 and ZEB2 genes are associated with survival in GC patients. PATIENTS AND METHODS: A total of 153 individuals with diagnosis of GC were recruited in Santiago, Chile. All patients were genotyped using Infinium Global Screening Array (GSA). Twenty Tag SNPs of the studied genes were retrieved. RESULTS: Three SNPs were associated with survival: rs2526614 (TWIST1) (genotype CA + AA, adjusted HR=0.58, 95%CI=0.37-0.93), rs6953766 (TWIST1) (genotype GG, crude HR=2.02, 95%CI=1.06-3.82, adjusted HR=2.14, 95%CI=1.07-4.25), and rs431073 (ZEB1) (genotype AC + CC, crude HR=1.62, 95%CI=1.01-2.59, adjusted HR=1.96, 95%CI=1.18-3.25). CONCLUSION: To the best of our knowledge, this is the first study proposing a role of these SNPs in cancer prognosis. Their use as prognostic markers of GC survival warrants further investigation.

Disminución en la frecuencia de infección por Helicobacter pylori en endoscopías digestivas altas / Helicobacter pylori infection detected during upper gastrointestinal endoscopy

Background: Helicobacter pylori (HP) is the most widespread chronic human infection worldwide and the most important pathogenic factor of gastric cancer. The calculated prevalence at the Clinical Hospital of the University of Chile from 2002 to 2005 was 44.9%. Aim: To determine the current prevalence of HP in patients undergoing an upper gastrointestinal endoscopy (UGI) and analyze its distribution according to age and endoscopic findings. Material and Methods: We reviewed 3.433 UGI performed during the year 2015, selecting those in which rapid urease test (RUT) was done. A positive RUT or a positive gastric biopsy (GB) were considered as HP infection. Results: RUT was done in 1862 UGI (55%) performed in patients aged 51 ± 17 years, (66% women). In 23% of these endoscopies, the RUT was positive. A GB was obtained 43% of endoscopies and 30% were positive for HP. In 105 patients the RUT was negative and the GB positive (rendering a 19.5% false negative rate). HP was detected by RUT and GB in 29% of endoscopies. The highest prevalence of infection (38.1%) was found between 40 and 49 years. HP infection had odds ratio of 4.24 for nodular gastropathy, 2.63 for gastric ulcer and 2.14 for duodenal ulcer (p < 0.05). Conclusions: HP prevalence in our center decreased significantly from 44.9% to 28.9% in 11 years. False negative RUT results may bias this finding. The use of proton pump inhibitors and antimicrobials that can interfere with the detection of HP should be registered to properly analyze the results of the RUT.

Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer.

The RAS/RAF/MEK/ERK pathway regulates certain cellular functions, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of this pathway leads to the occurrence and progression of cancers mainly by somatic mutations. This study aimed to assess if polymorphisms of the RAS/RAF/MEK/ERK pathway are associated with gastric cancer. A case-control study of 242 gastric cancer patients and 242 controls was performed to assess the association of 27 single nucleotide polymorphisms (SNPs) in the RAS/RAF/MEK/ERK pathway genes with gastric cancer. Analyses performed under the additive model (allele) showed four significantly associated SNPs: RAF1 rs3729931 (Odds ratio (OR) = 1.54, 95%, confidence interval (CI): 1.20⁻1.98, p-value = 7.95 × 10-4), HRAS rs45604736 (OR = 1.60, 95% CI: 1.16⁻2.22, p-value = 4.68 × 10-3), MAPK1 rs2283792 (OR = 1.45, 95% CI: 1.12⁻1.87, p-value = 4.91 × 10-3), and MAPK1 rs9610417 (OR = 0.60, 95% CI: 0.42⁻0.87, p-value = 6.64 × 10-3). Functional annotation suggested that those variants or their proxy variants may have a functional effect. In conclusion, this study suggests that RAF1 rs3729931, HRAS rs45604736, MAPK1 rs2283792, and MAPK1 rs9610417 are associated with gastric cancer.

Association of Chronic Pancreatitis and Malignant Main Duct IPMN: A Rare but Difficult Clinical Problem.

We report the case of a 70-year-old woman who consulted for recurrent short episodes of mild-to-moderate abdominal pain. Dilated main pancreatic duct was seen on CAT scan and magnetic resonance, with multiple calcifications and intraductal stones, typical in CP. However, for a more pronounced cystic dilatation in the pancreatic head, we could not exclude the coexistence of a main duct IPMN. ERCP was performed, with pancreatic sphincterotomy and extraction of pancreatic stones, but, at the same time, mucin extrusion was seen from the dilated duct through the papilla. Pancreatoduodenectomy was performed. Surgery and histology confirmed malignant IPMN with the typical image of chronic pancreatitis and intraductal stones in the vicinity. The patient is doing well 4 years after the surgery, without recurrence of the malignant disease, with changes of chronic pancreatitis in the pancreatic remnant. This paper discusses the possible relationships between the two entities and emphasizes the need of differential diagnosis.

Cólico biliar inducido por morfina / Morphine induced biliary pain: case report

Morphine produces contraction of Oddi’s sphincter, which can be severe and of longer duration in some pathological conditions. This exaggerated response can manifest as a colicky biliary pain, frequently accompanied by a dramatic increase in hepatic enzymes. We report a 32 years old female who consulted in the emergency room for severe low abdominal pain of gynecologic origin, which was completely controlled by morphine. However, she presented a sudden epigastric colicky pain irradiating in the back, which persisted for several hours in spite of the repeated administration of analgesics. Transaminases elevated from previously normal value to over 1,000 U/L, and returned to the normal level without further treatment after several days. Magnetic resonance cholangiography showed normal fine bile duct, without stones. This transient increase in hepatic enzymes was considered as a consequence of high biliary pressure secondary to morphine-induced spastic contraction of Oddi’s sphincter and a consecutive hepatocellular necrosis.