Early onset colorectal cancers, defined as arising before 50 years of age, are a growing health hazard in western and eastern countries alike. The incidence of colon and rectal cancers in young ...individuals is projected to increase by as much as 90% and 140%, respectively, by 2030. Although several known cancer risk factors (e.g. smoking, alcohol, dietary habits) have been investigated, there is no single compelling explanation for this epidemiological trend. While some early onset colorectal cancers have been associated with germline mutations in cancer predisposition genes, genetic syndromes are implicated in only a fraction of these cancers (20%) and do not explain the rising incidence.
Colorectal neoplasms develop through microsatellite instability or chromosomal instability pathways, with most of the early onset colorectal cancers exhibiting microsatellite stable phenotypes. Genome-wide hypomethylation is a feature of a subgroup of early onset cancers, which appears to be correlated with chromosomal instability and poor prognosis.
Colorectal cancer incidence and mortality in patients younger than 50 years are increasing, but screening before the age of 50 is not offered in Europe. Advanced-stage diagnosis and mortality from ...colorectal cancer before 50 years of age are increasing. This is not a detection-bias effect; it is a real issue affecting the entire population. Three independent computational models indicate that screening from 45 years of age would yield a better balance of benefits and risks than the current start at 50 years of age. Experimental data support these predictions in a sex- and race-independent manner. Earlier screening is seemingly affordable, with minimal impediments to providing younger adults with colonoscopy. Indeed, the American Cancer Society has already started to recommend screening from 45 years of age in the United States. Implementing early screening is a societal and public health problem. The three independent computational models that suggested earlier screening were criticized for assuming perfect compliance. Guidelines and recommendations should be derived from well-collected and reproducible data, and not from mathematical predictions. In the era of personalized medicine, screening decisions might not be based solely on age, and sophisticated prediction software may better guide screening. Moreover, early screening might divert resources away from older individuals with greater biological risks. Finally, it is still unknown whether early colorectal cancer is part of a continuum of disease or a biologically distinct disease and, as such, it might not benefit from screening at all. The increase in early-onset colorectal cancer incidence and mortality demonstrates an obligation to take actions. Earlier screening would save lives, and starting at the age of 45 years may be a robust screening option.
In uncomplicated diverticular disease, treatment is aimed at relieving symptoms. The aim of the present study was to evaluate the efficacy of mesalazine for symptomatic relief of uncomplicated ...diverticular disease of the colon. Two hundred sixty-eight consecutive eligible outpatients (122 male, 146 female; age, 66.1 years; range, 31-81 years) were enrolled in four treatment schedules in a randomized fashion: Group R1 (66 patients), rifaximin, 200 mg bid; Group R2 (69 patients), rifaximin, 400 mg bid; Group M1 (67 patients), mesalazine, 400 mg bid; and Group M2 (66 patients), mesalazine, 800 mg bid. Treatments were administered for 10 days every month for 12 months. Clinical evaluations were performed at admission and at 3-month intervals for 12 months considering 12 clinical variables (upper and lower abdominal pain/discomfort, tenesmus, diarrhea, abdominal tenderness, fever, bloating, general illness, nausea, emesis, dysuria, bleeding) graded as 0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe. The Global Symptomatic Score (GSS) was calculated using the sum of each symptom score. Two hundred forty-four patients completed the 12- month study; 24 were discontinued (14 treated with rifaximin and 10 treated with mesalazine) either as voluntary dropouts or because they developed side effects and/or complications. Group M2 demonstrated a lower frequency of many symptoms after 6 and 12 months of treatment; the mean GSS was significantly lower in Group M2 after 6 and 12 months of therapy by both intention-to-treat and per-protocol analyses. Patients treated with mesalazine (Groups M1+M2) had a lower GSS than subjects treated with rifaximin (Groups R1+R2) during the 12-month follow-up period. We conclude that cyclic administration of mesalazine is effective for symptomatic relief of uncomplicated diverticular disease of the colon. Some symptoms showed greater improvement with mesalazine, 800 mg bid, than with the other treatment schedules.
Early-onset colorectal cancer (EOCRC) is an increasing and worrisome entity. The aim of this study was to analyze its association with polyps concerning prognosis and surveillance. EOCRC cases were ...compared regarding the presence or absence of associated polyps (clinical and molecular features), during a minimum of 7 years of follow-up. Of 119 cases, 56 (47%) did not develop polyps (NP group), while 63 (53%) did (P group). The NP group showed a predominant location of the CRC in the rectum (50%), of sporadic cases (54%), and diagnosis at advanced stages: Only
and
mutations were statistically linked to this group. The P group, including mainly early-diagnosed tumors, was linked with the most frequent and differential altered chromosomal regions in the array comparative genomic hybridization. The two most frequent groups according to the follow-up were the NP group (40%), and patients developing polyps in the first 5 years of follow-up (P < 5FU) (34%) (these last groups predominantly diagnosed at the earliest stage and with adenomatous polyps (45%)). EOCRC with polyps that developed during the entire follow-up (PDFU group) were mainly located in the right colon (53%), diagnosed in earlier stages, and 75% had a familial history of CRC. Patients developing polyps after the first 5 years (P > 5FU) showed a mucinous component (50%). Our results show that the absence or presence of polyps in EOCRC is an important prognostic factor with differential phenotypes. The development of polyps during surveillance shows that it is necessary to extend the follow-up time, also in those cases with microsatellite-stable EOCRC.
To compare peptic ulcer prevalence in patients referred for upper gastrointestinal endoscopy in two Italian hospitals in pre-Helicobacter era and ten years after the progressive diffusion of ...eradication therapy.
We checked all the endoscopic examinations consecutively performed in the Gastroenterology Unit of Padova during 1986-1987 and 1995-1996, and in the Gastroenterology Unit of Parma during 1992 and 2002. Chi Square test was used for statistic analysis.
Data from both the endoscopic centers showed a statistically significant decrease in the prevalence of ulcers: from 12.7% to 6.3% (P<0.001) in Padova and from 15.6% to 12% (P<0.001) in Parma. The decrease was significant both for duodenal (from 8.8% to 4.8%, P<0.001) and gastric ulcer (3.9% to 1.5%, P<0.001) in Padova, and only for duodenal ulcer in Parma (9.2% to 6.1%, P<0.001; gastric ulcer: 6.3% to 5.8%, NS).
Ten years of extensive Helicobacter pylori (H pylori) eradication in symptomatic patients led to a significant reduction in peptic ulcer prevalence. This reduction was particularly evident in Padova, where a project for the sensibilization of H pylori eradication among general practioners was carried out between 1990 and 1992. Should our hypothesis be true, H pylori eradication might in the future lead to peptic ulcer as a rare endoscopic finding.
Background & Aims We investigated whether serum levels of pepsinogen (sPG)I and sPGII, the ratio of sPGI to sPGII, or serum levels of gastrin-17 (sG17), can be used to assess eradication of ...Helicobacter Pylori 8 weeks after treatment. Methods We performed a prospective study of 228 consecutive patients with H pylori infections. At the start of the trial (baseline), patients were assessed using the13 C-urea breath test (13 C-UBT) and endoscopy, and serum levels of pepsinogens and gastrin levels were measured. Patients were offered a 7-day triple therapy and asked to return 8 weeks after treatment for another13 C-UBT and measurements of serum levels of sG17, sPGI, and sPGII (175 patients completed the study). Results The eradication rate of H pylori was 67%. Percentage variation in levels of sPGI and sPGII, the ratio of sPGI to sPGII, and in levels of sG17 resulted in area under the curve values of 0.858, 0.973, 0.940, and 0.810, respectively, for H pylori eradication. A decrease of 22.7% or greater in the level of sPGII detected H pylori eradication with 100% sensitivity and 96.6% specificity. Spectrum analysis did not identify differences in accuracy. Conclusions Percentage variation of sPGII levels 8 weeks after therapy for H pylori infection correlates with eradication. Additional studies are needed to confirm these results.
The Atlanta classification of acute pancreatitis enabled standardised reporting of research and aided communication between clinicians. Deficiencies identified and improved understanding of the ...disease make a revision necessary.
A web-based consultation was undertaken in 2007 to ensure wide participation of pancreatologists. After an initial meeting, the Working Group sent a draft document to 11 national and international pancreatic associations. This working draft was forwarded to all members. Revisions were made in response to comments, and the web-based consultation was repeated three times. The final consensus was reviewed, and only statements based on published evidence were retained.
The revised classification of acute pancreatitis identified two phases of the disease: early and late. Severity is classified as mild, moderate or severe. Mild acute pancreatitis, the most common form, has no organ failure, local or systemic complications and usually resolves in the first week. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure, that is, organ failure >48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected). We present a standardised template for reporting CT images.
This international, web-based consensus provides clear definitions to classify acute pancreatitis using easily identified clinical and radiologic criteria. The wide consultation among pancreatologists to reach this consensus should encourage widespread adoption.
Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer ...risks according to gene and gender and to determine survival after cancer.
We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years.
There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer.
Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.
This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was ...started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.
In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer ...GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10
). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10
), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10
), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10
), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10
). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
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