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Infectious Diseases (London, England) 2019Fascioliasis is a tropical zoonotic disease caused by the parasite. The adult parasite usually resides in the liver and biliary ducts; however, several cases of ectopic...
Fascioliasis is a tropical zoonotic disease caused by the parasite. The adult parasite usually resides in the liver and biliary ducts; however, several cases of ectopic fascioliasis (EF) have been reported. This study is a highlight on EF according to the confirmed case reports. In a setting of systematic review, we found 25 eligible articles containing 26 confirmed cases of EF (any date until 30 November 2018), including abdominal and intestinal EF in six cases, skin and subcutaneous tissues in five cases, eye in four cases, brain and pancreas in three cases, neck and lymph node in two cases, and lung, dorsal spine, and peritoneal cavity in one case, respectively. The result indicates that fascioliasis can have diverse ectopic forms and should be more attended in the endemic regions of fascioliasis in order to distinguish from other endemic diseases.
Topics: Animals; Endemic Diseases; Fasciola; Fascioliasis; Humans; Zoonoses
PubMed: 31507248
DOI: 10.1080/23744235.2019.1663362 -
Journal of Lower Genital Tract Disease Apr 2019The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function,...
EXECUTIVE SUMMARY
The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available.
RESULTS
Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer.
RECOMMENDATIONS
The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunocompromised Host; Mass Screening; Middle Aged; Papillomavirus Infections; Practice Guidelines as Topic; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Neoplasms; Young Adult
PubMed: 30907775
DOI: 10.1097/LGT.0000000000000468 -
International Journal of Pediatric... Jun 2019Burkitt lymphoma (BL), an aggressive form of B-cell non-Hodgkin's lymphoma, arising from the nose and paranasal sinuses is relatively rare. It can present with various...
INTRODUCTION
Burkitt lymphoma (BL), an aggressive form of B-cell non-Hodgkin's lymphoma, arising from the nose and paranasal sinuses is relatively rare. It can present with various symptoms leading to potential misdiagnosis and delayed treatment. BL is fatal if left untreated, while early identification and treatment can improve prognosis.
OBJECTIVES
1) To review clinical presentations and sites of involvement of six cases of pediatric BL with rhinologic manifestations and compare these with the current literature. 2) To raise awareness on the variety of presentations of BL in this particular anatomic location.
METHODS
A series of six cases of pediatric (0-18 years) BL with rhinologic manifestations is presented. Age, sex, ethnicity, symptoms, imaging, staging, treatment and outcome were recorded. A systematic review of literature was also conducted using PRISMA guidelines. The search strategy used keywords related to rhinologic manifestations of BL (nasal cavity, nasopharynx, paranasal sinus etc.; Burkitt etc.) and included studies published in English and French describing patients 0-18 years of age.
RESULTS
42 patients were included (six from case series and 36 from current literature). Most common presenting symptoms were: nasal obstruction (29%), facial swelling (24%), headache (21%) and proptosis (19%). Most frequent sites of presentation were: nasopharynx (40%), maxilla (40%) and sphenoid (33%). More than half (60%) had systemic involvement, of which the most common locations were: kidney (19%), pancreas (17%) and liver (17%). Mortality from BL in children from this study population was correlated with a longer duration of symptoms prior to presentation, as well as a misdiagnosis preceding the final diagnosis of BL.
CONCLUSIONS
This study brings understanding to the numerous presentations of the same aggressive disease, promotes high clinical suspicion when evaluating common otolaryngologic symptoms and can guide healthcare providers in diagnosing pediatric BL with rhinologic manifestations.
Topics: Adolescent; Burkitt Lymphoma; Child; Child, Preschool; Edema; Exophthalmos; Face; Female; Headache; Humans; Infant; Kidney Neoplasms; Liver Neoplasms; Male; Maxilla; Nasal Obstruction; Nasopharynx; Pancreatic Neoplasms; Paranasal Sinuses
PubMed: 30897372
DOI: 10.1016/j.ijporl.2019.03.013 -
Langenbeck's Archives of Surgery Mar 2019Pancreaticoduodenectomy/PD is a technically demanding pancreatic resection. Options of surgical reconstruction include (1) the child reconstruction defined as... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Pancreaticoduodenectomy/PD is a technically demanding pancreatic resection. Options of surgical reconstruction include (1) the child reconstruction defined as pancreatojejunostomy/PJ followed by hepaticojejunostomy/HJ and the gastrojejunostomy/GJ "the standard/s-Child," (2) the s-child reconstruction with an additional Braun enteroenterostomy "BE-Child," or (3) Isolated-Roux-En-Y-pancreaticojejunostomy "Iso-Roux-En-Y," in which the pancreas anastomosis is reconstructed in a separate loop after the GJ. Yet, the impact of these reconstruction methods on patients' outcome has not been sufficiently compared in a systematic manner.
METHODS
A systematic review and meta-analysis were conducted according to the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines by screening Pubmed/Medline, Scopus, Cochrane Library and Web-of-Science. Articles meeting predefined criteria were extracted and meta-analysis was performed.
RESULTS
Nineteen studies were identified comparing BE-Child or Isolated-Roux-En-Y vs. s-Child. Compared to s-Child neither BE-Child (p = 0.43) nor Iso-Roux-En-Y (p = 0.94) displayed an impact on postoperative mortality, whereas BE-Child showed less postoperative complications (p = 0.02). BE-Child (p = 0.15) and Iso-Roux-En-Y (p = 0.61) did not affect postoperative pancreatic fistula/POPF in general, but BE-Child was associated with a decrease of clinically relevant POPF (p = 0.005), clinically relevant delayed gastric emptying/DGE B/C (p = 0.004), bile leaks (p = 0.01), and hospital stay (p = 0.06). BE-Child entailed also an increased operation time (p = 0.0002) with no impact on DGE A/B/C, hemorrhage, surgical site infections and pulmonary complications.
CONCLUSION
BE-Child is associated with a decreased risk for postoperative complications, particularly a decreased risk for clinically relevant DGE, POPF, and bile leaks, whereas Iso-Roux-En-Y does not seem to affect the clinical course after PD. Therefore, BE seems to be a valuable surgical method to improve patients' outcome after PD.
Topics: Aged; Anastomosis, Roux-en-Y; Cause of Death; Female; Humans; Male; Middle Aged; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications; Prognosis; Randomized Controlled Trials as Topic; Plastic Surgery Procedures; Reoperation; Risk Assessment; Survival Analysis; Treatment Outcome
PubMed: 30820662
DOI: 10.1007/s00423-019-01762-5 -
Journal of Laparoendoscopic & Advanced... Feb 2019Laparoscopic distal pancreatectomy with splenectomy is the standard procedure for body and tail pancreatic tumors. Technical difficulties arising from the strict... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laparoscopic distal pancreatectomy with splenectomy is the standard procedure for body and tail pancreatic tumors. Technical difficulties arising from the strict anatomical relationship between pancreas and splenic vessels generally impose a concomitant splenectomy. Previous retrospective studies have shown a reduced risk of postoperative complications and infections in spleen preserved patients, but this is still a debated issue. Aim of this systematic review and meta-analysis was to provide a more robust evidence on the effect of spleen preserving laparoscopic distal pancreatectomy.
METHODS
PubMed, MEDLINE, Embase, and Cochrane databases were consulted. Pooled effect measures were calculated using an inverse-variance weighted or Mantel-Haenszel in random effects meta-analysis. Heterogeneity was evaluated using I-index and Cochran Q-test.
RESULTS
Ten observational studies were eligible, and 632 patients were included in the quantitative analysis. Overall, 296 (46.8%) patients underwent laparoscopic distal pancreatectomy with splenectomy (Group S), and 336 (53.2%) patients underwent spleen-preserving laparoscopic distal pancreatectomy (Group SP). In-hospital mortality was 0%. In the group S, the estimated pooled odds ratio of postoperative surgical site infection (SSI) and overall complications was 1.51 (95% confidence interval [CI]: 1.01-2.28; P = .048) and 2.30 (95% CI: 1.11-4.76; P = .024). The estimated pooled odds ratio of pancreatic fistula, postoperative bleeding, and reoperation was 1.64 (P = .094), 1.01 (P = .987), and 1.24 (P = .776), respectively.
CONCLUSIONS
Spleen-preserving laparoscopic distal pancreatectomy may reduce postoperative SSI and overall complications. These results should be interpreted with caution but seem meaningful to establish a better evidence-based treatment for distal pancreatic tumors. Further studies are warranted to analyze the role of spleen preserving laparoscopic distal pancreatectomy on long-term outcomes.
Topics: Humans; Laparoscopy; Organ Sparing Treatments; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Postoperative Hemorrhage; Reoperation; Spleen; Splenectomy; Surgical Wound Infection
PubMed: 30592691
DOI: 10.1089/lap.2018.0738 -
The Cochrane Database of Systematic... Nov 2018Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures.Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery.This review was first published in 2012 and was updated in 2018.
OBJECTIVES
To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption.
SEARCH METHODS
We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention.We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies.
DATA COLLECTION AND ANALYSIS
We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study.Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate.In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low.Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate.All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term.
AUTHORS' CONCLUSIONS
This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term.Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.
Topics: Alcohol Abstinence; Alcohol Drinking; Elective Surgical Procedures; Female; Hospital Mortality; Humans; Male; Perioperative Care; Postoperative Complications; Preoperative Care; Randomized Controlled Trials as Topic; Secondary Prevention; Substance Withdrawal Syndrome; Surgical Procedures, Operative
PubMed: 30408162
DOI: 10.1002/14651858.CD008343.pub3 -
Transplantation Feb 2019There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOTs). One such...
BACKGROUND
There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOTs). One such promising marker is the presence of donor-derived cell-free DNA (dd-cfDNA) in the urine or blood of transplant recipients.
METHODS
We systematically reviewed the published literature investigating the use of cfDNA in monitoring of graft health after SOT. Electronic databases were searched for studies relating cfDNA fraction or levels to clinical outcomes, and data including measures of diagnostic test accuracy were extracted. Narrative analysis was performed.
RESULTS
Ninety-five articles from 47 studies met the inclusion criteria (18 kidneys, 7 livers, 11 hearts, 1 kidney-pancreas, 5 lungs, and 5 multiorgans). The majority were retrospective and prospective cohort studies, with 19 reporting diagnostic test accuracy data. Multiple techniques for measuring dd-cfDNA were reported, including many not requiring a donor sample. dd-cfDNA falls rapidly within 2 weeks, with baseline levels varying by organ type. Levels are elevated in the presence of allograft injury, including acute rejection and infection, and return to baseline after successful treatment. Elevation of cfDNA levels is seen in advance of clinically apparent organ injury. Discriminatory power was greatest for higher grades of T cell-mediated and antibody-mediated acute rejection, with high negative predictive values.
CONCLUSIONS
Cell-free DNA is a promising biomarker for monitoring the health of SOTs. Future studies will need to define how it can be used in routine clinical practice and determine clinical benefit with routine prospective monitoring.
Topics: Biomarkers; Cell-Free Nucleic Acids; Graft Rejection; Humans; Organ Transplantation; Tissue Donors
PubMed: 30308576
DOI: 10.1097/TP.0000000000002482 -
Pancreatology : Official Journal of the... Dec 2018Morphometric analysis of sarcopenia has garnered interest due to its putative role in predicting outcomes following surgery for a variety of pathologies, including... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Morphometric analysis of sarcopenia has garnered interest due to its putative role in predicting outcomes following surgery for a variety of pathologies, including resection for pancreatic disease. However, there are no standard recommendations on whether sarcopenia is a clinically relevant predictor of outcomes in this setting. The aim of this study was to review the prognostic impact of preoperatively diagnosed sarcopenia on postoperative outcomes following pancreatic resection.
METHODS
A systematic review of published literature was performed using PRISMA guidelines, and included a search of PubMed, MEDLINE and SCOPUS databases until May 2018.
RESULTS
Thirteen studies, including 3608 patients, were included. There was a significant increase in the mean duration of post-operative hospital stay (mean difference of 0.73 days, CI: 0.06-1.40, P = 0.033), there was no difference in the postoperative outcomes, including: clinically relevant postoperative pancreatic fistula, delayed gastric emptying, post-operative bile leak, surgical site infection, significant morbidity and overall morbidity.
CONCLUSION
Preoperative sarcopenia is associated with prolonged hospital stay after pancreatic surgery. However, sarcopenia does not appear to be a significant negative predictive factor in postoperative morbidity although study heterogeneity and risk of bias limit the strength of these conclusions.
Topics: Humans; Obesity; Pancreas; Pancreatectomy; Pancreatic Diseases; Postoperative Complications; Sarcopenia; Treatment Outcome
PubMed: 30287167
DOI: 10.1016/j.pan.2018.09.011 -
Asia-Pacific Journal of Clinical... Apr 2019This study is a systematic review and meta-analysis compare the short- and long-term outcomes of splenectomy (SP) versus splenic preservation (NSP) in radical gastric... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study is a systematic review and meta-analysis compare the short- and long-term outcomes of splenectomy (SP) versus splenic preservation (NSP) in radical gastric cancer surgery.
METHODS
A comprehensive search of PubMed, Embase, Cochrane Library and Web of Knowledge was performed. Evaluation of short- and long-term outcomes was collected and analyzed by a fixed or random effects model, according to the heterogeneity using RevMan 5.2 software.
RESULTS
A total of 5431 gastric cancer patients who underwent radical surgery (1706 with SP and 3725 with NSP) were reviewed in 11 studies included in this study. Compared with NSP, SP was significantly associated with higher rate of overall postoperative complication and increased incidence of pulmonary complications, abdominal abscess and pancreas complications. No statistical difference was observed regarding mortality, wound infection, anastomotic leakage and postoperative 5-year overall survival.
CONCLUSION
There was no difference in long-term oncological outcome but remarkably poorer short-term outcomes in SP group than NSP group. Therefore, SP seems unnecessary in radical gastric cancer surgery. However, well-designed, multicenter, prospective, randomized controlled trials are warranted for further validation.
Topics: Humans; Prospective Studies; Splenectomy; Stomach Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 30178572
DOI: 10.1111/ajco.13052 -
Pancreas Sep 2018Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate...
Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways. Twenty-two previously identified pancreatic cancer risk genes and 337 germline variants were identified from 97 informative studies that met our inclusion criteria. Fifteen of these genes contained 66 variants predicted to be pathogenic (APC, ATM, BRCA1, BRCA2, CDKN2A, CFTR, CHEK2, MLH1, MSH2, NBN, PALB2, PALLD, PRSS1, SPINK1, TP53). Pancreatic cancer risk genes were organized into key biological mechanisms that promote pancreatic oncogenesis within an oncogenic model. Development of precision medicine approaches requires updated variant information within the framework of an oncogenic progression model. Complex risk modeling may improve interpretation of early biomarkers and guide pathway-specific treatment for pancreatic cancer in the future. Precision medicine is within reach.
Topics: Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Pancreatic Neoplasms; Proto-Oncogene Proteins; Risk Assessment; Risk Factors
PubMed: 30113427
DOI: 10.1097/MPA.0000000000001136