Search

Background and Objectives : Colon cancer (CC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like matted nodes (lymph node conglomerates), are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of matted nodes in CC. Materials and Methods : From a retrospective analysis of 502 CC consecutive cases treated with colectomy (2005-2018), we identified 255 (50.8%) cases with lymph node metastasis (our study group), which were categorized into two groups: (1) lymph node metastasis alone (n = 208), and (2) lymph node metastasis with matted nodes (n = 47). A comparative survival analysis was performed. Results : Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for patients with matted nodes was 47.7%, compared to 60% without ( p = 0.096); however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and adjuvant chemotherapy use as independent factors contributing to survival. Conclusions : This study underscores matted nodes as potential prognostic indicators in CC, emphasizing their association with higher pN stage and reduced survival. Although the patients with matted nodes showed lower survival, this figure did not search statistical significance, but a tendency was detected, which necessitates precise further research, which is essential for validating these findings and integrating matted nodes into the broader context of colorectal cancer management.

Background: Matrix metalloproteinase 11 ( MMP11 ) plays a vital role in cell proliferation, apoptosis, tumor angiogenesis, migration, and other basic processes. Currently, few studies have examined the value of MMP11 in pancreatic cancer in relation to prognostic risk, diagnostic indicators, and immunotherapy. This study aims to explore the association between MMP11 and the tumor immune microenvironment in pancreatic adenocarcinoma (PAAD)., Methods: We selected clinical samples and data downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression, in addition, we use other online data for further analysis. Through a comprehensive bioinformatics investigation, we systematically analyzed the clinical significance and expression level of MMP11 in pancreatic cancer., Results: MMP11 was overexpressed in many cancers, and a higher expression of MMP11 was associated with a poorer prognosis in pancreatic cancer. Conversely, the hypermethylation of MMP11 was associated with better overall survival. The MMP11 expression network had widespread effects on the prognosis and immune activation of PAAD. The expression of MMP11 was significantly associated with a variety of tumor-infiltrating immune cells. An association was also found between MMP11 expression and chemokines in PAAD. High MMP11 expression might be involved in immune cell migration to the tumor microenvironment., Conclusions: MMP11 is a prognostic biomarker for patients in pancreatic cancer and may regulate the tumor immune microenvironment. The potential effects and mechanisms of MMP11 in PAAD require further exploring., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-425/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Synovial sarcoma (SS) and solitary fibrous tumor (SFT) are entities with considerable morphological and immunohistochemical similarities that sometimes show a non-confirmatory profile (TLE1 negative, CD34 and focal or negative STAT6 and lack of specific fusion IHC markers), in which the utility ultrastructure is unknown. A cross-sectional, retrospective, analytical, nonexperimental study was carried out by the Department of Pathology of the National Cancer Institute of Mexico (INCan) e from January 1, 2009 to December 31, 2018. With 17 SFT cases with diffuse or focal CD34 and STAT6 positivity and 18 cases of SS with positive FISH molecular test t(X:18) breakapart were studied by electron microscopy of fresh glutaraldehyde fixed or paraffin-embedded tissue. The ultrastructural findings with a significant difference present in the SS were tandem tight junctions, desmosomes and abundance of dilated rough endoplasmic reticulum (RER) cisternae ( p  < 0.001, 0.003, and 0.001, respectively); while in the (SFT) the presence of abundant glycogen, basal lamina, long and slender cytoplasmic processes, pinocytic vesicles, hemidesmosomes, and/or dense plaques, collagen skein, and microvilli-like buds ( p  = 0.028, 0.005, and <0.001 for the last five). We then infer that the five distinctive markers of the SFT are the collagen skeins intermingled with cellular processes in a shape of "squid can," and the pinocytic vesicles as they were not observed in any case of SS. Conversely, tandem junctions were not found in any SFT case. Although the presence of multivesicular buds in the SFT was not significant, it had not been previously described.

Background: Helicobacter pylori (Hp) infection is highly prevalent globally and is predominantly managed by antibiotics. Recently, the anti-adhesive, antioxidant, antitoxin, immunomodulatory, anti-coagulant, and anti-infective activities of fucoidan, a polysaccharide extracted from brown seaweeds, have been widely studied, and the results showed promise. Fucoidan has the potential to be utilized in Hp eradication therapy. Our present clinical study was designed to evaluate the efficiency of Lewuyou ® , a fucoidan plant drink (FPD) in eradicating Hp in humans., Methods: This multi-center, clinical study was conducted between October 2020 and July 2021. Hp infection was confirmed by urea breath test (UBT). A total of 122 patients with confirmed Hp infection were enrolled; after exclusion of incomplete data, 85 eligible patients (37 males and 48 females aged 20-81 years) were included in the final analysis. FPD (50 mL per vial) was orally administered twice daily for a 4-week cycle, and 41 patients completed an 8-week cycle., Results: No adverse event (AE) was reported in all 122 participants who had consumed FPD. The Hp eradication rate and clearance rate were 77.6% (66/85) and 20.0% (17/85), respectively, after 4 weeks of FPD consumption and 80.5% (33/41) and 26.8 (11/41) , respectively, after 8 weeks of consumption., Conclusions: The 4- and 8-week protocols of FPD consumption were safe and effective at reducing Hp load on the gastric mucosa, with Hp eradicated in the majority of participants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-63/coif). All authors report that Blue Regale Clinical Nutrition Technology Co., Ltd. provides product support for this study. QHP is from Blue Regale Clinical Nutrition Technology Co., Ltd., Kunshan, China. The authors have no other conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer., (© 2023. BioMed Central.)

Background: Dysphagia is the most frequent symptom in patients diagnosed with esophageal cancer. Self-expanding metal stents (SEMS) are the current palliative treatment of choice for dysphagia in patients with non-curable esophageal cancer. This study aimed to evaluate the efficacy and adverse events (AEs) of different types of SEMS for palliation of dysphagia., Methods: We performed a retrospective cohort study of patients with advanced esophageal cancer and SEMS placement for dysphagia palliation in a tertiary care center. The primary outcome was the clinical success defined as an improvement in dysphagia (reduction of at least 2 points in the Mellow-Pinkas scoring system for dysphagia) after SEMS placement., Results: Between January 1999 and May 2020, 295 patients with esophageal cancer were identified. Among them, 75 had a SEMS placement for dysphagia palliation. The mean age of the patients was 61.3 years (standard deviation: 13.4), 69 patients (92%) were men, and the mean Mellow-Pinkas scoring for dysphagia pre- and post-SEMS placement were 3.1 and 1.4 (change from baseline -1.7), respectively. Technical success and clinical success were achieved in 98.6% and 58.9%, respectively. AEs were identified in 35/75 patients (46.7%), and SEMS migration was the most frequent AE in 22/75 patients (29.3%). There were no significant differences in improvement in dysphagia ( p  = 0.054), weight changes ( p  = 0.78), and AE ( p  = 0.73) among fully covered SEMS (fc-SEMS) and partially covered SEMS (pc-SEMS). The median follow-up was 89 days (interquartile range: 29-221)., Conclusion: SEMS placement was associated with a rapid improvement in dysphagia, high technical success, and a modest improvement in dysphagia with no major AE among fc-SEMS and pc-SEMS., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Background: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors., Methods: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors., Results: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45)., Conclusion: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems., Trial Registration: researchregistry7882., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent., Methods: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS)., Results: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031)., Conclusions: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values., (© 2023. The Author(s).)

Background: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colon cancer. However, there is no information of their survival impact in rectal cancer with neoadjuvant chemoradiotherapy (n-CRT)., Methods: Retrospective study in 223 patients with rectal cancer with n-CRT. A survival analysis of factors associated with decreased overall survival (OS) including TDs was performed., Results: From 223 patients, 131 (58.7%) were men, mean age 59.8 (± 13.06) years, and 42 (18.8%) of them revealed TDs. Survival analysis of TDs showed no association with mortality. Factors associated with decreased 5-year OS were the histologic grade (p = 0.42), perineural invasion (p = 0.001), and mesorectal quality (p = 0.067). Perineural invasion (HR = 2.335, 95% CI = 1.198-4.552) remained as independent factor in the multivariate analysis., Conclusions: TDs were not associated with mortality in rectal cancer patients treated with n-CRT. Factors associated with decreased survival were inadequate mesorectal quality and perineural invasion., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polypoid melanoma is considered an exophytic and frequently non-pigmented variant of nodular melanoma with an adverse prognosis; however, very few studies have been published about it with contradictory results. Therefore, our objective was to determine the prognostic value of this configuration in melanomas. A transversal retrospective study of 724 cases was analyzed according to the main configuration (polypoid vs. non-polypoid) regarding their clinicopathologic characteristics and survival analysis. Of the 724 cases, 35 (4.8%) met the definition of polypoid melanoma; such cases, compared with non-polypoid melanomas, were associated with a high Breslow thickness (7 mm vs. 3 mm), 68.6% had a Breslow >4 mm; showed different clinical stages of presentation, and presented more ulceration (77.1 vs. 51.4%). In the 5-year overall survival (OS) analysis, polypoid melanoma is associated with a lower 5-year OS, together with lymph node metastasis, Breslow thickness, clinical stage, mitoses per mm 2 , vertical growth phase, ulceration, and state of the surgical margins; however, in the multivariate analysis, the factors that remained independent predictors of death were the Breslow thickness groups, the clinical stage, the presence of ulceration, and the state of the surgical margins. Polypoid melanoma was not an independent predictor of OS. We found a prevalence of 4.8% of polypoid melanomas, which showed a worse prognosis than non-polypoid melanomas, explained by a higher proportion of ulcerated cases, greater Breslow thickness, and ulceration. However, polypoid melanoma was not an independent predictor of death., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours., Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186., Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039)., Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants ( path&#95;MMR ) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time., Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path&#95;MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender., Findings: Gynaecological cancers were more frequent than colorectal cancers in path&#95;MSH2, path&#95;MSH6 and path&#95;PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path&#95;MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path&#95;MMR carriers undergoing colonoscopy surveillance, particularly path&#95;MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers., Interpretation: In path&#95;MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome., Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017., Competing Interests: R.B. has received honoraria for lectures and advisory boards from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Illumina, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, and Targos MP Inc. R.B. is a Co-Founder and Scientific Advisor for Targos Mol. Pathology Inc. Kassel/Germany. T.T.S. is the CEO and co-owner of Healthfund Finland Oy and reports consultation fees from Boehringer Ingelheim Finland and Amgen. FB is supported by JANSSEN PHARMACEUTICALS (clinical trial for Familial Adenomatous polyposis). RH is supported by the 10.13039/501100002424Fujifilm Germany and Janssen-Pharmaceuticals. LK is consultant of Sandoz, Novartis and Abbott. GM reports consultancy fees from Johnson & Johnson., (© 2023 The Author(s).)

Introduction: Appropriate size of resection margins in acral melanoma is not clearly established., Objective: To investigate whether narrow-margin excision is appropriate for thick acral melanoma., Methods: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm)., Results: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003)., Conclusion: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma., (Copyright: © 2023 Permanyer.)

Background: Apatinib is approved in China for the treatment of advanced gastric adenocarcinoma that had progressed or relapsed after standard systemic chemotherapy treatments. However, the effectiveness of Apatinib under real-world condition has not been evaluated and the drug performance under ideal and controlled circumstances has not been validated. In fact, genetic factors, poor healthcare access, social economic status, comorbidities compliance and other factors play significant role in drug performance under "real-world" conditions. Real-world experience can help validate the safety and efficacy of apatinib., Methods: In this observational, prospective study we evaluated the safety and efficacy of Apatinib in patient treated in China. Between March 2018 and March 2019, a total of 943 patients with gastric cancer treated with Apatinib were enrolled. Response Evaluation Criteria in Solid Tumors, version 1.1 and Common Terminology Criteria for Adverse Events, version 4.0 were used to evaluate efficacy and adverse effects., Results: The median progression-free survival (PFS) was 5.65 months (5.22-6.05 months), and the median overall survival (OS) was 11.47 months (10.41-12.52 months). Apatinib in combination with more than two agents was superior to single agent apatinib in overall response rate (ORR) [18.18% vs. 9.43%, 95% confidence interval (CI): 1.03-5.90] and disease control rate (DCR) (82.82% vs. 77.87%, 95% CI: 1.21-2.59). Apatinib in combination with single agent chemotherapy was also superior to apatinib alone with DCR (86.29% vs. 77.87%, 95% CI: 1.47-2.99) irrespective of the dose (250 or 500 mg). In the patient cohort who received a starting dose of 250 mg, the DCRs of the combined treatment and monotherapy groups were 86.22% vs. 80.00% (95% CI: 1.18-3.09), respectively. The most common treatment-emergent adverse events were anemia, anorexia and thrombocytopenia (66.28%, 37.75%, 36.06%, respectively)., Conclusions: Efficacy of Apatinib in this observational study is promising and toxicities are manageable. Combination of Apatinib with chemotherapy agents has a higher response rate and better disease control at the expense of increased serious adverse events. Better OS can be achieved by receiving apatinib treatment earlier. As a supplement and further validation of explanatory randomized controlled trials, the real-world study reflects the real efficacy of apatinib in practical application., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5995/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Cutaneous melanoma is an aggressive neoplasm with growing incidence and continuous research is undertaken for novel prognostic factors. This current research aims to determine if tumor budding is an independent factor that correlates with the survival of patients with melanoma. A total of 742 cases of melanoma were evaluated. A receiver operating curve (ROC) was performed to analyze tumor budding impact on survival, identifying a cutoff point associated with death. Subsequently, two groups of participants were created based on that result. Participants within the two groups were compared for clinicopathologic characteristics and survival analysis. Also, a multivariate analysis was performed. Of the total, 447 (60.2%) melanomas occurred in women and 295 in men. The mean age was 57.5 years + 15.75. The most common location was in acral areas (68.2%) followed by trunk (16.7%) and head and neck (15.1%). At presentation, 142 cases (19.1%) presented as stage I, 307 (41.4%) as stage II, 269 (36.3%) as stage III, and 24 (3, 2%) in stage IV. Regarding tumor budding, 586 (79%) cases showed tumor budding (at least one bud in 0.785 mm 2 ), with a median of 5. From the ROC curve, 4.5 tumor buds/0.785 mm 2 was the best cutoff point for correlation with death, grouping the series in low budding (0-4 buds/0.785 mm 2 ) and high budding ( > 5 buds/0.785 mm 2 ). Cases with high tumor budding were associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death. High tumor budding was associated with a significant decrease in 5-year overall survival (94.4% vs. 55.5%, P < 0.001). In the multivariate analysis, the factors remaining as independent predictors of survival were acral location, clinical stage IV, recurrence during clinical follow-up, and high tumor budding. High tumor budding (>5 buds in 0.785 mm 2 ) independently correlates with 5-year overall survival rates and is associated with older age, acral location, advanced clinical stages, ulceration, recurrence, and death., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants., Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path&#95;MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path&#95;MMR carriers who were first- or second-degree relatives of Lynch syndrome probands., Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path&#95;MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path&#95;MSH2 50% and 39%; for path&#95;MSH6 13% and 17% and for path&#95;PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups., Conclusions: Prospectively observed CRC incidences (PLSD) in path&#95;MLH1 and path&#95;MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path&#95;MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path&#95;PMS2 carriers subjected to colonoscopy, but not significantly so., (© 2022. The Author(s).)

Background: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a transmembrane receptor that has a complex role in cancer, acting either to promote or inhibit tumor progression in different tumor types. The effect of ROR2 on gastric cancer is unclear., Methods: Immunohistochemistry was used to investigate the role of ROR2 in the prognosis of gastric cancer. Transwell assay and a BALB/c nude mice pulmonary metastasis model were used to ascertain the role of ROR2 in promoting metastasis in vitro and in vivo . A protein expression array, chromatin immunoprecipitation (ChIP) assay, and luciferase reporter assay were employed to search for the target genes of ROR2., Results: ROR2 was found to be upregulated in gastric cancer tissues, which was correlated with poor disease-free survival (DFS) and overall survival (OS) in gastric cancer patients. Moreover, ROR2 promoted gastric cancer cell migratory and invasive behaviors in vitro and metastasis in vivo . Further research showed that ROR2 promoted gastric cancer metastasis via upregulation of matrix metalloproteinase 3 (MMP3). Analyses of clinical data indicated that high expression of ROR2 was correlated with a high expression of MMP3. Further study showed that ROR2 activated c-JUN by translocating phosphorylated JNK1/2 into the nucleus, and c-JUN interacted directly with the MMP3 promoter, leading to enhanced MMP3 transcription., Conclusions: We report for the first time that ROR2 is upregulated in gastric cancer, promotes metastasis, and is associated with poor prognosis in gastric cancer. The findings suggest that ROR2 may be a promising prognostic predictor for gastric cancer. Silencing the JNK1/2-c-JUN pathway, thereby inhibiting MMP3 expression, may serve as a promising strategy to inhibit gastric cancer progression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4583/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is highly malignant due to its late diagnosis and early metastasis. Lung metastasis of PDAC occurs in a significant number of diagnosed patients and represents high severity of disease and poor clinical outcome. However, the molecular regulation of lung metastasis of PDAC is still not fully understood. Tumor-associated macrophages (TAMs) have recently been found to play an important role in cancer initiation, proliferation, progression, and metastasis. The proliferation, differentiation, and polarization of macrophages has been shown to be regulated by interleukin 1β (IL-1β), which is generated by NLR family pyrin domain containing 3 (NLRP3)-induced formation of inflammasome. Herein we investigated whether NLRP3 plays a role in lung metastasis of PDAC through regulation of macrophage polarization., Methods: Gene profiles for NLRP3 (+/+) and NLRP3 (-/-) macrophages obtained from the Gene Expression Omnibus (GEO) public database were compared and analyzed for altered genes related to macrophage polarization. The regulation of macrophage polarization by NLRP3 was examined in a coculture system with naïve NLRP3 (+/+) or NLRP3 (-/-) macrophages and PDAC cells. Cell growth was analyzed by a Cell Counting Kit-8 (CCK-8) assay. Cell invasiveness and migratory potential were analyzed by transwell cell invasion assay and cell migration assay, respectively. PDAC formation and lung metastasis were analyzed in a mouse model of PDAC with and without NLRP3 knockout., Results: GEO database analysis revealed significant alteration in genes that regulate macrophage polarization in NLRP3-depleted macrophages. NLRP3-depletion in macrophages seemed to favor an M1/M2b polarization. In vitro , the presence of NLRP3 in macrophages led to M2a/c/d TAM-like polarization when they were cocultured with PDAC cells. Conversely, NLRP3 depletion in macrophages led to M1/M2b polarization when they were cocultured with PDAC cells. NLRP3-depletion significantly inhibited tumor growth and stage progression in a mouse model of PDAC and significantly reduced the occurrence of lung metastasis., Conclusions: Our results suggested that NLRP3 activation in TAM enhanced lung metastasis of PDAC through regulation of TAM polarization., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-311/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center., Materials and Methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center., Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/μL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1., Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Introduction: Peritoneal tuberculosis (abdominal tuberculosis) can be confused with a malignant neoplasm., Objective: To describe clinical and demographic characteristics of patients with abdominal tuberculosis mimicking advanced ovarian cancer, diagnosed in a national reference cancer center., Methods: Clinical and pathological characteristics of nine patients with abdominal tuberculosis that clinically resembled advanced ovarian cancer are described., Results: Median age was 47 years; the most common socioeconomic status was low (44%). Abdominal pain and weight loss occurred in 77.7%; ascites, in 55.5%; 22.2% had a positive COMBE test, and 100% had no history of pulmonary tuberculosis. CA-125 elevation was reported in 77.7%, with levels > 500 U/mL in 57.1%. Tomography reported carcinomatosis in 50% and pelvic tumor and ascites in 37.5%. All patients underwent surgery, where 62.5% were diagnosed by intraoperative pathology study as neoplastic disease., Conclusion: Tuberculosis is considered the great imitator, which is why abdominal tuberculosis diagnosis should be borne in mind when faced with a suspicious case, even when clinical presentation, imaging studies, and even intraoperative examination suggest ovarian cancer., (Copyright: © 2022 Permanyer.)

Background: Soft tissue sarcomas (STS) are a heterogeneous group of rare tumours that represent less than 1% of all malignant, solid tumours in adults. There is limited epidemiological information regarding STS in Latin America. Therefore, the objective of this study is to present an epidemiological profile of these tumours observed at a single reference centre., Methods: A retrospective study was carried out based on hospital records obtained from a registry of 879 patients with STS of the extremities who were treated at the National Cancer Institute of Mexico from January 1, 1994 to December 31, 2017. Epidemiological variables and relevant clinical data were collected. Five-year survival rates were analysed using Kaplan-Meier estimates, and a multivariate Cox proportional-hazards model measured associations., Results: A total of 879 records were collected. The median age was 45 years (15-95 years), and the ratio of men to women was 1:1, with 433 men (49.3%), and 446 women (50.7%). The median tumour size was 11.4 cm (2-49 cm). The most prevalent histological variants were liposarcomas and synovial sarcomas. The lower limb was the most frequently affected extremity, with the thigh being the most common site followed by the leg. A majority of the patients were diagnosed at clinical stages IIIA-IV., Conclusions: The data collected from the present cohort provides an overview of the epidemiological profile of STS at a single reference centre in Latin America, and allow comparison with global data., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Borderline ovarian tumors (BTs) must be recognized during the surgery by intraoperative consultation (IOC) to guide surgical treatment; however, this diagnosis can be imprecise. Therefore, this study aimed to evaluate the diagnostic accuracy of IOC for the diagnosis of BT., Methods: A retrospective cohort study was carried out including all women diagnosed with a pelvic tumor consecutively surgically treated from 2005 to 2015 with IOC. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) for the IOC and BTs., Results: A total of 758 patients were enrolled, the median age was 44 years, the median tumor size was 11.8 cm, and the median CA-125 levels were 45.65 U/µL. After IOC, 458 (64.1%) cases were diagnosed as benign, 111 (14.7%) as BT, and 161 (21.2%) as malignant. The definitive diagnosis was a benign tumor in 448 (59.1%) cases, BT in 110 (14.5%), and 200 (26.4%) cases were malignant. The diagnostic accuracy of the IOC for BT diagnosis was 89.8% (sensitivity =65.5%, specificity =93.9%). The diagnosis performance of IOC for the diagnosis between BT and benign tumors (n=546) had a sensitivity of 69.9%, a specificity of 98.4%, and a diagnostic accuracy of 84%; meanwhile for the diagnosis between BT and malignant tumors (n=242) IOC had a sensitivity of 92.3%, a specificity of 81.7%, and a diagnostic accuracy of 87%., Conclusions: For practitioners, knowing the accuracy and limitations of the IOC for BT enables the better selection of cases to perform a complete staging surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3932). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.

Introduction: Obesity has been linked with an increased incidence of melanoma; however, there are few data about its impact on melanoma prognosis. We aimed to determine if there is an association between body mass index (BMI) and overall survival (OS) in 707 patients with melanoma., Material and Methods: A retrospective study of 707 patients with melanoma collected consecutively from 2005 to 2015 with a diagnosis of melanoma, who were been diagnosed and treated in our institution and who had clinical follow-up was carried out. Survival analysis was performed comparing patients according to their BMI., Results: In a multivariate analysis, factors influencing the 5-year OS were a positive margin (HR = 3.475, 95% CI: 1.829-6.600), the clinical-stage (HR = 2.565, 95% CI: 2.020-3.257, per switch to the upper stage), ulceration (HR = 3.475, 95% CI: 1.829-6.600), and BMI (HR .905, p = 0.018 for the overweight group; HR = 0.663, p = 0.021 for obesity grade I)., Conclusions: Patients who had a BMI between 25 and 34.9 kg/m 2 had better survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Introduction: Lymph node (LN) dissection is an important prognostic factor in gastric cancer. There is little information comparing the LN count depending on whether they are dissected in the operating room or in the pathology laboratory., Aim: To establish if the LN count is greater in either of them., Material and Methods: From 2015 to 2017 all consecutive gastrectomies with D2 dissection were prospectively evaluated based in either of 2 protocols: One started in the operating room where the surgeon separated the LN levels and then submitted the entire adipose tissue with LNs (undissected) to pathology in separate containers; the pathologist dissected the LNs from the specimens. The second protocol consisted of sending the tissue/LNs to pathology as usual (adipose tissue and LN attached to the stomach)., Results: A total of 83 patients were analysed. The mean age was 58.4 years. The median number of LNs dissected in the protocol starting in the operating room was 56 (IQR: 37-74), whereas the pathology laboratory dissected a median of 39 LNs (IQR 26-53) ( p = 0.005). The survival of cases dissected by both protocols were comparable (median survival of 48 and 43 months, p = 0.316)., Conclusions: The LN final count is significantly higher when LN levels are separated beforehand in the operating room compared to dissection only in pathology; however, this does not impact survival, perhaps because the number of dissected nodes in both groups is high and the quality of the surgery is good., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Gastric cancer is a common and deadly cancer. Several factors are associated with its prognosis; however, controversy exists about the role of microsatellite instability (MSI). We aimed to determine the 5-year overall survival (OS) of MSI in gastric adenocarcinoma. A cross-sectional study was carried out on gastric adenocarcinoma in clinical stages I to III treated with D2 gastrectomy between 2010-2013. MSI was demonstrated by immunohistochemistry. We performed a survival analysis comparing cases with and without MSI. From 102 cases, 9.8% showed MSI. The median age was 63 years (range 33-91 years), and 57.8% were men. The more prevalent site of occurrence was the antrum (46.1%), 78.5% of the cases presented in stage III, 47.1% were of the diffuse type, 45.1% were of an intestinal type, and 7.8% were mixed. MSI cases were associated with lower clinical stages (stages I-II) and with better 5-year OS (100 vs. 47 months, p = 0.017). In a multivariate analysis, MSI was independently associated with better survival (HR = 0.209, 95% CI: 0.046-0.945, p = 0.042). MSI gastric cancers presented in early clinical stages and had favourable prognosis compared with non-MSI cancers., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Background: Melanoma epidemiological and prognostic studies are based on Caucasian populations, in whom the predominant subtype is superficially-spreading melanoma and in whom thin melanomas (Breslow < 3 mm) predominate. Mexican patients show a predominance of thick melanomas (Breslow ≥ 3 mm), and the acral subtype is the most common. There are no publications on prognostic factors in thick melanomas. We hypothesize that we will identify factors that determine the prognosis in this group of patients., Objective: To identify clinical-pathological factors associated with the prognosis of patients with thick melanomas in the Mexican population., Material and Methods: Data on melanomas with Breslow > 3 mm were collected from 2010 to 2015. The prognostic influence of various clinical-pathological factors was analyzed., Results: The most common subtypes were acral melanoma in 271 patients (74.9 %) and nodular melanoma in 49 (13.5 %). Median Breslow thickness was 7 mm. 56.6 % of the patients had lymph node metastases (clinical stage [CS] III), 269 (74.3 %) had ulceration, and surgical margins were positive in 15 (4.1 %). Elevated neutrophil: lymphocyte ratio (≥ 2) was found in 188 (51.9 %). The variables associated with lower overall survival were CS (p < 0.001), Breslow thickness (p = 0.044), ulceration (p = 0.004), mitotic activity (p < 0.001), < 2-cm margin (p < 0.001) and an increased neutrophil: lymphocyte ratio (p = 0.037). In the multivariate analysis, the factors associated with overall survival were CS, mitotic activity, and surgical margin., Conclusions: In patients with thick melanomas, overall survival is influenced by mitotic activity, a positive margin, and clinical stage., (Copyright: © 2021 Permanyer.)

Artificial intelligence (AI) is a complex technology with a steady flow of new applications, including in the pathology laboratory. Applications of AI in pathology are scarce but increasing; they are based on complex software-based machine learning with deep learning trained by pathologists. Their uses are based on tissue identification on histologic slides for classification into categories of normal, nonneoplastic and neoplastic conditions. Most AI applications are based on digital pathology. This commentary describes the role of AI in the pathological diagnosis of the gastrointestinal tract and provides insights into problems and future applications by answering four fundamental questions.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5088). The authors have no conflicts of interest to declare.

Ovarian carcinoma is highly aggressive and difficult to treat neoplasm, which is usually detected in advanced stages where most patients recur. Extensive investigation about several treatment modalities has been performed but this neoplasm has poor benefits from such treatments including targeted therapy. Recent data have begun to highlight the histological and molecular heterogeneity of these tumors defining this neoplasm, not as a single disease but a group of heterogeneous histological subtypes with important differences in terms of genetics, morphology, oncogenesis, prognosis, chemosensitivity and especially molecular characteristics that are likely to be targets of new molecules. In general, high-grade serous carcinomas are characterized by great genomic instability and frequent amplifications and deletions; lowgrade ovarian neoplasms are genomically stable. On this phytopathogenic basis, recent findings suggest a dual model of carcinogenesis consisting of two large groups named types I and II. Type I cancers (serous, mucinous, and low-grade endometrioid) commonly arise from well-described, genetically stable precursor lesions (usually borderline tumors); manifests as large adnexal masses with the early-stage disease, and they have a good overall prognosis. In contrast, type II carcinomas (serous, high-grade endometrioid, mixed, and undifferentiated carcinomas) originate de novo from the adnexal epithelium, often demonstrate chromosomal instability, and have aggressive biological behavior. Surprisingly, most of the genomic abnormalities detected encode known oncogenic proteins for which there is targeted therapy. Then, there is a real potential for personalized medicine adapted to the molecular portrait of tumors. In this review, I synthesize the histology and molecular pathology of ovarian carcinomas and possible strategies to reach targeted therapy.

Background: Evaluating tumor response of rectal cancer to preoperative chemoradiotherapy (NCRT) has a prognostic value on overall survival; however, grading tumor response is a controversial issue due to lack of reproducibility and the lack of information about the standardization of the evaluation., Methods: We performed this study to examine the variability between observers' assessment of the pathological responses to NCRT using a systematic quantitative grading system based on a percentage of tumor response against the proportion of residual tumor burden. As a secondary aim, we classified the tumor response according to six published systems to determine the correlation between the observers into each grading system., Results: From 70 cases, the mean age was 60.6 ± 11.78 years, 36 (51.47%) patients were female, the pathological T stage was pT3 in 48.6% of cases, pT2 in 32.9%, pT1 in 11.4% and 7.1% in pT4, whereas 40% had lymph node metastasis. The median lymph node count was ten lymph nodes (range 6-43). Our method of tumor regression evaluation has a good intraclass correlation (ICC) value. From the scales compared regarding interobserver agreement, the Ryan's and Royal College of Pathologists showed fair agreement (but good ICC); the scales from Dworak, Becker, and Rizk showed substantial agreement (and good to excellent ICC values); and the scale from Rödel showed almost-perfect agreement., Results: All the evaluated systems showed good interobserver agreement, but the best interobserver agreement was reached with the Rödel's scale.

Background: BRAF evaluation is currently limited to molecular techniques, which are expensive and not widely available to practicing pathologists. Our objective was to determine the diagnostic performance of immunohistochemistry (IHC) against BRAF V600E for BRAF mutation and the secondary objective was determining histopathological characteristics of colon carcinomas with BRAF mutated., Methods: Cases of adenocarcinoma of the colon with a known BRAF mutation status were identified from the pathological files of our institution., Results: We analyzed 135 cases, 13 cases had the BRAF mutation (9.6%) and 122 were non-mutated. The mutated cases expressed intense and diffusely the anti-antibody against BRAF V600E, and 119 (97.5%) of the 122 cases without mutation were negative and the remaining 3 were focal and weakly positive. The IHC demonstrated a sensitivity of 100%, specificity of 97.5%, positive predictive value of 81.3% (95% CI = 56.9 to 93.4%), negative predictive value of 100% (95% CI = 89 to 100%), and an overall accuracy of 97.8%. The only significant clinicopathological differences between cancers with BRAF mutated compared with BRAF non-mutated were that mutated had less lymph node metastases (23% vs. 68.1%) and the tumor size was greater (median 90 mm vs. 60 mm). The survival between groups was not statistically significant., Conclusion: IHC against BRAF V600E showed an excellent performance, making it feasible as an alternative for molecular examination. Tumors with BRAF mutated did not show distinctive clinico-pathological characteristics, except for a larger tumor size.

Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting., (Copyright: © 2020 Permanyer.)

Introduction and Aim: Mantle cell lymphoma is an aggressive subtype of B-cell non-Hodgkin lymphoma and its incidence is 0.5/100,000 inhabitants. Gastrointestinal involvement at diagnosis is 15-30%. The aim of our study was to analyze the clinical and endoscopic characteristics of mantle cell lymphoma affecting the digestive tract., Material and Methods: A retrospective study was conducted, based on a case series of patients with mantle cell lymphoma affecting the gastrointestinal tract that were diagnosed over a 10-year period., Results: Ten patients (11.7%) had gastrointestinal tract involvement. The upper endoscopic findings were polypoid lesions (66%), thickened folds (44%), and nonspecific changes in the mucosa (33%). At colonoscopy, polypoid lesions were viewed in 100% of the patients and ulcerated lesions in 40%., Conclusion: Polypoid lesions are the most common endoscopic characteristics in patients with mantle cell lymphoma of the gastrointestinal tract. Upper endoscopy and colonoscopy should be carried out on patients with mantle cell lymphoma, even those with nonspecific symptoms, to check their gastrointestinal status. Gastrointestinal involvement has an impact on disease staging., (Copyright © 2018 Asociación Mexicana de Gastroenterología. All rights reserved.)

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path&#95;MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path&#95;MSH2 were identified in 37% of females and males, followed by path&#95;PMS2 in 11% of females and 8% of males, path&#95;MSH6 in 13% of females and 3% of males (p < 0.001) and path&#95;EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pancreatic adenocarcinoma (PAC) is a health problem because of high lethality, increasing incidence and the absence of an early diagnosis. Biopsy by fine needle aspiration guided by endoscopic ultrasound has allowed obtaining tissue for cytopathological analysis, but there are several problems with their interpretation. We aimed to compare the diagnostic performance of the cytopathological analysis with the addition of either an immunohistochemical (IHC) panel or the KRAS mutation for the diagnosis of PAC., Methods: We evaluated 62 pancreatic lesions by fine needle aspiration guided by endoscopic ultrasound, applying an IHC panel with mucin (MUC)-1, MUC4, carcinoembryonic antigen (CEA) and p53. All cases also had a KRAS mutation determination. Three cytopathologists blinded to clinical data and the KRAS status reviewed the cytology independently. We calculated diagnostic performances for the cytology alone, cytology+IHC and cytology+KRAS to show the best method to diagnose PAC., Results: From 62 samples, 50 (80.6%) were PAC and 12 benign lesions. The cytopathological analysis correctly interpreted 26 malignant and 12 non-neoplastic cases (sensitivity 52%, specificity 100% and diagnostic accuracy 61.3%). The KRAS mutation was present in 88% of PAC. The cytology+ KRAS mutation increased the sensitivity by 10% and the diagnostic accuracy by 8%. The sensitivity increased by 2% adding either MUC1 or CEA to the cytology, and the diagnostic accuracy by 10 or 18%, respectively., Conclusion: The addition of IHC either with CEA or MUC1 improved the diagnostic performance of the cytology alone to diagnose PAC. The cytology + IHC evaluation was superior to the cytology + KRAS mutation to diagnose PAC., (© 2019 John Wiley & Sons Ltd.)

Purpose: Gastrointestinal stromal tumors (GIST) have the potential to recur and metastasize. Several prognostic schemes have been developed, mostly based on the mitotic count, diameter, and tumor site. However, these systems are not precise enough. The research question was whether the tumor size determined by volumetry allows a better risk stratification than the traditional system, and our aim was to determine the value of tumor volumetry, a feasible and simple parameter, in the recurrence of GIST., Methods: Seventy-four cases of GIST were studied. The cases presented with non-metastatic disease, which were resected and did not receive imatinib. We compared the clinico-pathologic features of the cases with recurrence against those with non-recurrence and compared the tumor volumetry against the classification system based on tumor size and mitosis., Results: The median age was 58 years (range: 25 to 91 years). Half of the cases were presented in the stomach. The tumor size had a median of 8 cm (range of 1-30 cm). The median mitosis count for 50 HPF was 4 (range 0-92). During the period of study, 16 (21.6%) patients suffered recurrence. The significant differences were that patients with recurrence accounted for more deaths and the follow-up period was larger. The area under the curve (AUC) of the volumetry classification was superior to the AUC of the classification system based on tumor size and mitosis (NIH-criteria) (p = .05)., Conclusion: Tumor volumetry calculated in the surgical specimen and/or pre-operative tomography was superior to the NIH consensus in stratifying the risk of recurrence in GIST.

Background and Objectives: Tumor deposits (TDs) are associated with adverse prognostic factors and decreased survival in colorectal cancer. However, controversy exists regarding their definition, evaluation, and staging categories. This study aimed to determine the survival and recurrence impact of the TD in colon adenocarcinomas; and to determine if TD patients behave similarly to stage IV patients., Methods: Cross-section study from 392 patients with colon adenocarcinoma from 2005 to 2012. We performed survival analysis and further stratified patients considering TD patients as a "stage IV-TD" to demonstrate if they behave similarly than stage IV patients., Results: From 392 patients, 204 (52%) were men, the mean age was 57.4 ± 13.9 years and 11.5% of cases had TD. In a multivariate analysis, TD failed to predict mortality and recurrence. Considering cases with TD as stage IV-TD, their mean survival was similar to stage IV patients (69.3 and 64.6 months, respectively) and different to those in stage III (110.5 months), II (135.7 months), and I (114.9 months) (P < 0.001)., Conclusions: TD failed to predict mortality and recurrence. Patients with TD in stage I-III shows similar mortality than stage IV patients; then, we suggest putting them into a substage IV category instead of the N1c category., (© 2019 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path&#95;MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path&#95;MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path&#95;MSH6 and path&#95;PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path&#95;MLH1 and path&#95;MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Factors associated with the time to surgery (TTS) and survival in colon cancer (CC) have not been well studied. Our aim was to find if the TTS has changed in our institution over time and to determine if it influences the survival., Methods: Retrospective cross-section study of 266 CC analyzed between two periods, and according to the quartiles of TTS, we performed a survival analysis., Results: The median age was 57 years; there was no predominance of sex, and about half of the patients were in stage III. The median TTS was 38 days, and 75% of the cases were operated before 60 days. The median TTS for 2005 to 2010 was 36 days, while for 2011 to 2015 was 41 days (P = 0.107). The survival was not statistically different between cases (1) operated with a delayed TTS or not, (2) operated in four cut-off points of TTS, (3) two different periods of attention, and (4) according to the clinical stage., Conclusion: We did not find an association between the TTS with low survival. TTS has increased in the last period so we must work to make the diagnostic process more efficient in our patients to meet international quality standards., (© 2018 Wiley Periodicals, Inc.)

Background: Cervicovaginal cytology as a follow-up study in women with a history of a cervical carcinoma treated with chemo-radiotherapy (CRT) plays an important role; however, the cytomorphological characteristics for the diagnosis of high-grade squamous intraepithelial lesions (H-SIL) in post-CRT patients have not been established. The aim of the study is to find the cytomorphological characteristics that support the diagnosis of H-SIL by conventional cytology in these patients., Materials and Methods: This is a cross-sectional study from 2009 to 2015, which includes patients with a diagnosis of squamous cell carcinoma treated with CRT, who all have cervix cytology for follow-up and a later biopsy., Results: We identified 82 cases, where the most frequent clinical stage was IIA1 to IIB with 26 cases (61.9%), the most common symptom was transvaginal bleeding (64.29%). The cytological characteristics that were statistically associated with the presence of a positive biopsy were the presence of a hemorrhagic background (45.2% vs. 12.5%, P = .007), high cellularity (45.2% vs. 15%, P < .001), disposition in groups/sheets (69% vs. 22.5%, P < .001), postradiotherapy changes at the background of the smear (73.8 vs. 50%, P < .001) and an increased nuclear/cytoplasmic ratio (100% vs. 22.5%, P < .001)., Conclusions: In patients with CRT, the presence of specific features can help the diagnosis of H-SIL with excellent diagnostic performance., (© 2018 Wiley Periodicals, Inc.)

Introduction:: Acral lentiginous melanoma (ALM) is an aggressive variant of melanoma; the incidence, prevalence, and prognosis differ among populations. We analyzed clinicopathological features and survival in Hispanics, a population with high ALM prevalence., Material and Methods:: From 1144 patients with melanoma, we analyzed 715 ALMs and 429 non-ALMs from the National Referral Cancer Centre and compared survival., Results:: Of the ALM group, 62.8% were female; the median age was 58 years. The mean Breslow thickness was 3.56 ± 7.16 mm. ALM patients showed an estimated 5-year disease-specific survival (DSS) of 53.3%, 52.7%, and 40.8% for stage I, II, and III, respectively. For non-ALM patients, the DSS rates were 66%, 60.8%, and 48.4% for stage I, II, and III disease, respectively. Overall, the 1-, 3-, and 5-year DSS rates for patients with ALM were 85.1%, 59.4%, and 46.3%, respectively; for non-ALM patients, they were 81.3%, 64.8%, and 55.7%, respectively ( P = .168). In the multivariate analysis, factors associated with decreased DSS were high Breslow thickness, recurrence, ulceration, male sex, and advanced stage., Conclusions:: The 1-, 3-, and 5-year DSS rates of patients with ALM were not statistically different from those of non-ALM patients. In addition to known adverse prognostic factors, male sex was also associated with worse survival.