colorectal cancer is one of the most common malignancies in developed countries. Data on specific and 10-year survival are scarce. This study analyzes overall and disease-specific survival for ...patients with colorectal cancer and assesses the value of clinical factors on disease-specific survival.
a retrospective cohort study of newly diagnosed invasive colorectal cancer cases diagnosed from 1992 to 2007 were identified through the Hospital del Mar Cancer Registry. Five-and 10-year survival functions were estimated using Kaplan-Meier method. Cox proportional hazard models were used to assess prognostic factors.
a total of 2,080 patients with colorectal cancer were identified. The median age at diagnosis was 72 years and 58.5%were men. By the end of the follow-up period (December 2008), 1,225 patients had died and 68.4% of deaths were due to colorectal cancer. The 5- and 10-year cancer-specific survival rates were 55.5% (95%CI 53.9-57.9%) and 48.5% (95%CI 45.6-51.3%), respectively. The 5-year specific survival rate improved in the last period (2003-2007) (60.4%, 95%CI 55.4-65.0) compared with 1992-1997(53.4%; 95%CI 49.2-57.4) and 1998-2002 (52.0%; 95%CI 47.8-56.2). Various factors were independently associated with excess CRC mortality: male sex (HR 1.21), age at diagnosis > 75 years(HR 1.97), rectal location (HR 1.33), more advanced stages (stage IV: HR 18.54), poorly differentiated/undifferentiated tumors (HR 1.80), and admission through the emergency department (HR 1.52).
cancer-specific survival improved from 1992 to 2007. This improvement could be due to more effective treatment, since changes in stage distribution or age at diagnosis were not observed during the study period. Overall survival rates should notably improve with the implementation of a population-based colorectal cancer screening program in Spain.
BACKGROUND // Pleural mesothelioma is a neoplasm almost exclusively attributed to occupational exposure to asbestos and is
legally considered an occupational disease. Nevertheless, only a few cases ...achieve that official recognition. The objective of this work
was to describe and analyse this issue, and to identify the major obstacles to its recognition.
METHODS // A descriptive and retrospective epidemiological study of data was carried out, including figures and some characteristics,
of all patients with pleural mesothelioma registered in the official health and labor registries of the Valencian Community from 2012 to
2018, using frequencies, proportions, and incidence rates.
RESULTS // There were large differences between the two sets of data collected in the different registries, especially regarding the
number of cases. During the seven years of data examined, 590 pleural mesotheliomas were diagnosed in the Valencian public health
system. Of these, the number of cases that were related to occupational exposure was at least 437. Despite the legal duty of doctors
to report such cases, only 31 were reported as suspected occupational disease (7.09%), of which only 13 were ultimately officially
recognized as such. It was estimated that the annual economic overcost to the public system of unrecognised patients with this
occupational disease by was 2,2270,520 euros.
CONCLUSIONS // Only a small proportion of occupational mesotheliomas are officially recognized as such. This has important
health care and economic repercussions for the individuals involved as well as for the public health system.
FUNDAMENTOS // El mesotelioma de pleura es un cáncer atribuido casi en exclusiva a la exposición laboral al amianto y que tiene
la consideración legal de enfermedad profesional, aunque pocos casos consiguen ese reconocimiento oficial. Describir y analizar este
problema y los obstáculos para su reconocimiento fue el objetivo de este trabajo.
MÉTODOS // Se realizó un estudio epidemiológico descriptivo y retrospectivo de las cifras y algunas características de todos los pacientes
de mesotelioma de pleura recogidos en los principales registros oficiales, sanitarios y laborales, de la Comunidad Valenciana,
desde 2012 a 2018, utilizando frecuencias, fracciones y tasas de incidencia.
RESULTADOS // Hubo grandes diferencias en el número de casos recogidos en los distintos registros. En los siete años estudiados,
los mesoteliomas de pleura diagnosticados en el sistema sanitario público valenciano fueron 590. De ellos, aplicando la fracción
atribuible al trabajo con amianto, al menos 437 fueron atribuibles al trabajo. Los facultativos comunicaron 31 casos como sospechas
de enfermedad profesional, el 7,09% del total, y, finalmente, 13 casos se reconocieron oficialmente como enfermedad profesional. El
coste económico estimado de su atención sanitaria para el sistema público valenciano fue de 2.270.520 euros.
CONCLUSIONES // Una mínima parte de los mesoteliomas obtienen el reconocimiento de enfermedad profesional. Este hecho
conlleva importantes repercusiones asistenciales y económicas para las personas afectadas y para el sistema sanitario público.
Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA ...mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H).
Background
Instruments that enable to select individuals that will benefit most from bariatric surgery (BS) are necessary to increase its cost-efficiency. Our goal was to assess if intake capacity, ...measured with a standardized test, predicts response to BS.
Methods
Patients with criteria for BS were randomly allocated to laparoscopic gastric bypass (LRYGB) or sleeve gastrectomy (LSG). We measured caloric intake capacity before and 1 year after surgery using a standardized nutrient drink test. We evaluated if pre-surgery satiation could predict satiation and weight loss (%) 1 year after surgery using multiple regression modeling. Descriptive statistics are given as mean ± SD.
Results
Fourteen women (48 ± 9 years old, BMI 41 ± 3 kg/m
2
) were evaluated before and 11 ± 2.6 months after surgery (seven LRYGB, seven LSG). Caloric intake capacity diminished after surgery (−950 ± 85 kcal on average 70 ± 8 % decrease over basal intake capacity;
p
= 0.002) and similarly in both LRYGB (72 ± 7 % decrease) and LSG groups (68 ± 8 % decrease);
p
= 0.5. There was a significant weight reduction after surgery (-32 ± 10 kg 30 ± 8 % of total basal weight) with a mean post-surgery BMI of 29 ± 2 kg/m
2
. The best predictive model of weight loss (%) after surgery (
R
2
= 89 %,
p
= 0.0009) included: BMI (
p
= 0.0004), surgery type (
p
= 0.01) and pre-surgery intake capacity (
p
= 0.006). Weight loss was higher in heavier patients and those undergoing LRYGB. Patients with higher intake capacity had a poorer outcome independently of basal BMI and surgery type.
Conclusions
Caloric intake capacity, as measured by a standard nutrient drink test, helps to predict weight loss after bariatric surgery. This test might be useful in algorithms of obesity treatment decision.
In the last two decades, the incidence of esophageal cancer has progressively increased, especially that of adenocarcinomas localized in the esophagogastric junction. The incidence of gastric cancer ...has decreased in the last few decades, although this decrease shows wide geographical variations. Thus, the prevalence of gastric cancer continues to be high in countries such as Chile, Colombia and Ireland and this disease remains the most frequent neoplasm in both sexes in China and Japan. In the meeting of the American Gastroenterological Association, notable among all the studies presented on the prevention and treatment of esophageal and gastric cancer were the following contributions: the use of clinical practice guidelines for the prevention and surveillance of Barrett's esophagus (BE) should be improved; treatment with proton pump inhibitors does not seem to reduce the risk of esophageal cancer; endoscopic therapy of intramucosal cancer through complete mucosal resection is effective; Helicobacter pylori eradication prevents the development of metachronous gastric cancer in patients treated for a first intramucosal adenocarcinoma through endoscopic resection; the risk of developing gastric cancer is 6 times higher in patients with mucosa-associated lymphoid tissue (MALT) lymphoma than in the general population; and photodynamic therapy may be an alternative for the treatment of "invisible" gastric adenocarcinoma, which should be followed-up endoscopically.
Nuclear IKKα regulates gene transcription by phosphorylating specific substrates and has been linked to cancer progression and metastasis. However, the mechanistic connection between tumorigenesis ...and IKKα activity remains poorly understood. We have now analyzed 288 human colorectal cancer samples and found a significant association between the presence of nuclear IKK and malignancy. Importantly, the nucleus of tumor cells contains an active IKKα isoform with a predicted molecular weight of 45 kDa (p45-IKKα) that includes the kinase domain but lacks several regulatory regions. Active nuclear p45-IKKα forms a complex with nonactive IKKα and NEMO that mediates phosphorylation of SMRT and histone H3. Proteolytic cleavage of FL-IKKα into p45-IKKα is required for preventing the apoptosis of CRC cells in vitro and sustaining tumor growth in vivo. Our findings identify a potentially druggable target for treating patients with advance refractory CRC.
Display omitted
► A truncated active form of IKKα is found in colorectal cancer cells ► Nuclear complex containing p45-IKKα phosphorylates SMRT and histone H3 ► Cleavage of IKK(alpha) into p45-IKKα is required for cancer cell growth
Nuclear IKKa regulates gene transcription by phosphorylating specific substrates, a role linked to cancer and metastasis. However, the mechanistic connection between tumorigenesis and IKKa activity remains poorly understood. Espinosa and colleagues now identify a 45 kDa active nuclear isoform of IKKa (p45-IKKa) that associates with nonactive IKKa and NEMO to inhibit SMRT corepressor activity. Proteolytic cleavage of IKKa into p45-IKKa is required in order to sustain tumor growth in vivo. These findings identify a possible druggable target for treating patients with advanced refractory colorectal cancer.
The potential protective effect of renin–angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). ...To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48–0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66–0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.
•Angiotensin-converting enzyme inhibitors protect against colorectal cancer.•This effect is limited to males and people under 65years old.•The stronger association is observed in proximal colon.
PDF
