Publications by authors named "Leonardo S Lino-Silva"

47 Publications

Epidemiological profile of soft tissue sarcomas of the extremities: Incidence, histological subtypes, and primary sites.

J Orthop 2021 May-Jun;25:70-74. Epub 2021 Apr 2.

National Cancer Institute (Instituto Nacional de Cancerología) Mexico City, Mexico.

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.
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http://dx.doi.org/10.1016/j.jor.2021.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079324PMC
April 2021

The usefulness of intraoperative consultation for the diagnosis of borderline ovarian tumors.

Ann Transl Med 2021 Feb;9(3):261

Surgical Oncology, National Cancer Institute, Mexico City, Mexico.

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.
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http://dx.doi.org/10.21037/atm-20-3932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940902PMC
February 2021

IMMUNOTHERAPY TREATMENT AGAINST CERVICAL CANCER.

Rev Invest Clin 2020 ;72(4):231-238

Department of Clinical Research, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

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.
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http://dx.doi.org/10.24875/RIC.20000060DOI Listing
January 2020

Artificial intelligence technology applications in the pathologic diagnosis of the gastrointestinal tract.

Future Oncol 2020 Dec 5;16(34):2845-2851. Epub 2020 Sep 5.

Anatomic Pathology, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico.

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.
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http://dx.doi.org/10.2217/fon-2020-0678DOI Listing
December 2020

Tumor deposits in colorectal cancer: the need for a new "pN" category.

Ann Transl Med 2020 Jun;8(12):733

Surgical Oncology, Instituto Nacional de Cancerología, Tlalpan, Mexico City, Mexico.

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http://dx.doi.org/10.21037/atm.2020.03.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333091PMC
June 2020

Ovarian carcinoma: pathology review with an emphasis in their molecular characteristics.

Chin Clin Oncol 2020 Aug 20;9(4):45. Epub 2020 May 20.

Surgical pathology, Instituto Nacional de Cancerología, Mexico City, Mexico.

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.
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http://dx.doi.org/10.21037/cco-20-31DOI Listing
August 2020

Interobserver Variability in Assessing Pathologic Response to Preoperative Treatment in Rectal Cancer: Standardization of an Evaluation Method and Comparisons Between Published Scales.

J Gastrointest Cancer 2020 Jun;51(2):709-713

Surgical oncology, National Cancer Institute, Mexico City, Mexico.

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.
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http://dx.doi.org/10.1007/s12029-019-00331-9DOI Listing
June 2020

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries.

Eur J Cancer 2019 09 20;119:112-121. Epub 2019 Aug 20.

Hospital de Especialidades Eugenio Espejo, Subproceso de Anatomía Patológica, Área de Genética Clínica, Quito, Ecuador.

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_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_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.
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http://dx.doi.org/10.1016/j.ejca.2019.07.017DOI Listing
September 2019

Report of three cases of gastric choriocarcinomas-an emphasis on morphologic changes in the non-affected gastric mucosa.

J Gastrointest Oncol 2019 Aug;10(4):810-814

Surgical Oncology, Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.

Primary gastric choriocarcinomas (PGC) are very rare and aggressive neoplasms with a worrisome prognosis. Most cases are reported in Asia and presented in middle-aged adults with male predominance. Most cases are associated with an intestinal adenocarcinoma; however, the pathogenesis of this tumor is uncertain. No previous reports exist of the characteristics of the non-tumoral stomach in these patients, and this data that could help to clarify their pathogenesis. We presented a series of three cases of PGC in Latin American patients, emphasizing the characteristics of non-neoplastic mucosa.
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http://dx.doi.org/10.21037/jgo.2019.01.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657320PMC
August 2019

Stage I-III colon cancer patients with tumor deposits behave similarly to stage IV patients. Cross-section analysis of 392 patients.

J Surg Oncol 2019 Aug 24;120(2):300-307. Epub 2019 Apr 24.

Surgical Oncology, Instituto Nacional de Cancerología, Mexico, Mexico.

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.
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http://dx.doi.org/10.1002/jso.25482DOI Listing
August 2019

Addition of analysis of KRAS mutation or immunohistochemistry with MUC1 and carcinoembryonic antigen improves the diagnostic performance of fine needle aspiration cytology for the diagnosis of pancreatic carcinoma.

Cytopathology 2019 09 23;30(5):485-491. Epub 2019 Apr 23.

Unit of Biomedical Research in Cancer, Institute of Biomedical Research, National Autonomous University of Mexico.

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.
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http://dx.doi.org/10.1111/cyt.12697DOI Listing
September 2019

BRAF V600E Expression by Immunohistochemistry in Colon Cancer and Clinico-pathologic Features Associated with BRAF-Mutated Colonic Cancers in Mexican Patients.

J Gastrointest Cancer 2020 Mar;51(1):35-40

Surgical Oncology, Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.

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.
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http://dx.doi.org/10.1007/s12029-018-00191-9DOI Listing
March 2020

Prognostic importance of lymph node ratio after resection of ampullary carcinomas.

J Gastrointest Oncol 2018 Dec;9(6):1144-1149

Surgical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico.

Background: The prognosis of the lymph node ratio (LNR) in Vater's ampulla carcinomas (VACs) is recently studied. However, there are not enough data in several populations like Latin American people. Our aim is to demonstrate the prognosis significance of the LNR in this setting.

Methods: Pancreaticoduodenectomies for VACs were identified (n=128) from 1980 through 2015. Based on a ROC curve, a cut-off point of 0.1 was assigned for the LNR and the population was divided into two groups for comparison.

Results: The LNR ≥0.1 group was statistically significant associated with recurrence (38.5% 19.5%), pT3-T4 tumors (69.2% 29.3%), poorly differentiated tumors (46.2% 17.5%), lymphovascular invasion (61.5 17.1%), perineural invasion (38.5% 19.5%), and positive margins (15.4% 2.4%). In the multivariate analysis, LNR (HR 2.891; CI: 1.987-3.458, P=0.02), LNM (HR 2.945; CI: 2.478-3.245, P=0.002), perineural invasion (HR 3.327; CI: 3.172-4.156, P=0.003), and recurrence (HR 3.490; CI: 2.896-4.122, P=0.001) were associated with lower survival.

Conclusions: The LNR is a good predictor of survival and worse oncological outcomes for VACs after resection.
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http://dx.doi.org/10.21037/jgo.2018.07.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286937PMC
December 2018

Overall survival of patients with colon cancer and a prolonged time to surgery.

J Surg Oncol 2019 Mar 24;119(4):503-509. Epub 2018 Dec 24.

Department of Surgical Pathology, Gastrointestinal Pathology Division, Instituto Nacional de Cancerología, Mexico City, Mexico.

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.
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http://dx.doi.org/10.1002/jso.25354DOI Listing
March 2019

Interobserver variability in colorectal cancer and the 2016 ITBCC concensus.

Mod Pathol 2019 01 19;32(1):159-160. Epub 2018 Dec 19.

Surgical Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico.

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http://dx.doi.org/10.1038/s41379-018-0027-5DOI Listing
January 2019

Reclassification of lesions in biopsies by fine-needle aspiration of pancreas and biliary tree using Papanicolaou classification.

J Gastrointest Oncol 2018 Oct;9(5):847-852

Department of Cytopathology, Hospital General de Mexico "Gerardo Liceaga", Mexico City, Mexico.

Background: Our aim was to evaluate the application of the classification of the Papanicolaou Cytopathology Society for the report of biopsies by fine-needle aspiration (FNA) of pancreas and bile duct.

Methods: The FNAs obtained consecutively during 1 year were analyzed. Descriptive statistics were performed and sensitivity, specificity, positive predictive value, negative predictive value, and cytohistological correlation were determined. The reference standard test was the histopathological study.

Results: A total of 134 cases of FNA were reclassified with ultrasound guidance according to the classification of the Papanicolaou Society, the median age was 59 years (range, 25-80 years). A case interpreted as non-diagnostic was reclassified to category 4 and 3 cases with atypical cells were reclassified to category 5. All malignant cases remained unchanged. Surgical follow-up was performed in 35 patients (26.1%), with a cytohistological concordance in 21 cases (91.3%) and 2 discordant cases (8.7%), the reasons for the discrepancy were due to sampling error, one of them with scarce material to make a diagnosis of higher category, the other case with partial agreement, because cytology was observed atypical cylindrical epithelium, with histology of grade 2 neuroendocrine neoplasia and low grade mucinous intraepithelial neoplasia. In general, the sensitivity and specificity were 100% and 75% respectively, the positive predictive value 88% and the negative predictive value 100%.

Conclusions: The FNA guided with endoscopic ultrasound (EUS) and interpreted according to the Papanicolaou Cytopathology Society Classification is an accurate method to evaluate pancreatic and biliary tract lesions with a high positive predictive value of 88%.
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http://dx.doi.org/10.21037/jgo.2018.06.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219961PMC
October 2018

Cytomorphological features of high-grade intraepithelial neoplasia/carcinoma of the cervix following chemoradiotherapy.

Diagn Cytopathol 2019 Mar 23;47(3):194-199. Epub 2018 Nov 23.

Gynecologic Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico.

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.
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http://dx.doi.org/10.1002/dc.24070DOI Listing
March 2019

Overweight but not obesity is associated with decreased survival in rectal cancer.

Contemp Oncol (Pozn) 2018 30;22(3):158-164. Epub 2018 Sep 30.

Hospital Angeles, Tijuana, Mexico.

Aim Of The Study: To analyse the influence of overweight and obesity in disease-specific survival (DSS) in rectal cancers at stages I-III in a population with high prevalence of overweight/obesity.

Material And Methods: The population ( = 304) consisted of Mexican patients with stage I-III rectal cancer during the period between 2009 and 2015. Patients were divided based on their body mass index (BMI) into normal weight 18-25 kg/m, overweight 25-29 kg/m, and obesity BMI > 30 kg/m groups. Comparison of clinicopathologic features and survival analysis were performed.

Results: The median age was 58 years (interquartile range [IQR] 50-65) and the mean BMI was 26.03 ±4.06 kg/m. Patients in the obesity and overweight groups received a lower proportion of preoperative treatment and had a higher proportion of patients in stage II. Overweight patients had a lower baseline neutrophil/lymphocyte ratio and lower survival rate than patients with normal weight and with obesity (mean survival of 69.5 months vs. 81.15 months and 86.4 months, respectively). The estimated five-year DSS was 51% for the overweight group, 81% for the normal group, and 82% for the obesity group ( = 0.026).

Conclusions: Patients with stage I-III rectal cancer in the overweight group showed a lower DSS compared to groups with normal weight and with obesity, with the last two being similar.
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http://dx.doi.org/10.5114/wo.2018.78937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238088PMC
September 2018

Mismatch repair protein expression and intratumoral budding in rectal cancer are associated with an increased pathological complete response to preoperative chemoradiotherapy: A case-control study.

World J Clin Oncol 2018 Nov;9(7):133-139

Surgical Oncology, Instituto Nacional de Cancerología, Mexico City 14080, Mexico.

Aim: To determine whether the association of rectal adenocarcinoma with a defective-mismatch repair system (dMMR) was associated with a pathological complete response (pCR) to preoperative chemoradiotherapy.

Methods: A case-control study was designed with the aim of determining if patients with rectal adenocarcinoma with dMMR had an associated high pCR rate in response to neoadjuvant chemoradiotherapy (nCRT).

Results: Seventy-two cases with pCR were compared against 144 controls without pCR. Across 216 cases, the mean age was 56.8 years, 140 (64.8%) were men, and 63 (29.2%) demonstrated the dMMR system. The pCR was associated with G1 tumors, dMMR, the absence of vascular invasion, and low tumor budding in the pretreatment biopsy. In a multivariant analysis, the factors associated with pCR were dMMR (OR: 2.61; 95%CI: 1.355-5.040, = 0.004) and a low degree of tumor budding (OR: 2.52; 95%CI: 1.366-4.894, = 0.025).

Conclusion: We found an independent association between dMMR and a low rate of tumor budding, with a higher rate of pCR, in the basal biopsies of patients with rectal carcinoma subjected to nCRT.
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http://dx.doi.org/10.5306/wjco.v9.i7.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230920PMC
November 2018

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Int J Cancer 2019 07 5;145(2):318-326. Epub 2018 Dec 5.

AC Camargo Cancer Center, Sao Paulo, Brazil.

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_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_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_MLH1 and path_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.
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http://dx.doi.org/10.1002/ijc.31920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587543PMC
July 2019

Acral Lentiginous Melanoma: Survival Analysis of 715 Cases.

J Cutan Med Surg 2019 Jan/Feb;23(1):38-43. Epub 2018 Sep 15.

3 Surgical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

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.
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http://dx.doi.org/10.1177/1203475418800943DOI Listing
June 2019

Tumour budding in rectal cancer. A comprehensive review.

Contemp Oncol (Pozn) 2018 30;22(2):61-74. Epub 2018 Jun 30.

National Institute of Medical Sciences and Nutrition, Mexico City, Mexico.

A unique and fundamental characteristic of malignant neoplastic cells is their ability to invade other tissues and metastasise. The first step in this process is the dissociation of some of these cells from the tumour invasion front, named tumour budding (TB). This phenomenon has become increasingly relevant in recent years due to its association with adverse clinicopathological characteristics and with the epithelial-mesenchymal transition. TB has been studied by mixing colon with rectal tumours, but it is clinically important to differentiate these types of tumours. A review in two databases without language restriction was performed from 1950 to 2017 about TB with an emphasis on rectal cancer. We present various aspects of TB, from its terminology and evaluation to its molecular aspects, through its clinical associations. TB is associated with adverse clinicopathological features, like lymphovascular invasion, lymph node metastasis, and decreased survival. More studies of the clinicopathological, molecular, and epidemiological characteristics of TB in rectal cancer are needed.
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http://dx.doi.org/10.5114/wo.2018.77043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103233PMC
June 2018

Association of ki67 Index with Recurrence in Gastrointestinal Stromal Tumors.

J Gastrointest Cancer 2018 Dec;49(4):543-547

Surgical Oncology, Instituto Nacional de Cancerología, Mexico City, Mexico.

Purpose: Gastrointestinal stromal tumors (GIST) have the potential to recur and metastasize. Several prognostic schemes have been developed but none are precise enough and most times the pathologist faces a small biopsy where it is not possible to evaluate the mitotic count. Our aim was to determine the influence of ki67 index and other clinicopathologic characteristics in the recurrence of GIST.

Methods: Forty-three consecutive cases of GIST were studied. The cases presented with non-metastatic disease. We compared the clinicopathologic features of cases with recurrence against those with non-recurrence. The ki67 index was determined by square-millimeters.

Results: The median age was 55 years (IQR 45-63), the most frequent site of involvement was the stomach with 21 (48.8%) cases, and the median of tumor diameter was 10 cm (IQR 5.5-17.5). Twenty-six (60.5%) cases were spindle cell, 13 (30.2%) were mixed, and 4 (9.3%) were epithelioid. The median mitosis count for 50 high power fields was 4 (IQR 0-16), while per square millimeter it was 1 (IQR 0-5, range 0-32). The median of the ki67 proliferation index was 5% (IQR 1-20). During the period of study, 11 (25.6%) patients recurred. The only significant differences between patients with GIST with recurrence and without recurrence were the sex and tumor size.

Conclusion: We did not find an association of the ki67 index with recurrence. The factors associated with recurrence were a high tumor size (> 10 cm) and male sex.
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http://dx.doi.org/10.1007/s12029-018-0150-zDOI Listing
December 2018

Frequency of Defective Mismatch Repair System in a Series of Consecutive Cases of Colorectal Cancer in a National Cancer Center.

J Gastrointest Cancer 2018 Sep;49(3):379-384

Surgical oncology, Instituto Nacional de Cancerología, Mexico City, Mexico.

Background: The frequency of colorectal cancer (CRC) with defective mismatch repair (dMMR) is estimated between 5 and 15%. In our population, the frequency of dMMR is unknown. Our objective was to show the frequency of dMMR.

Methods: Determination of dMMR with immunohistochemistry was performed prospectively for 202 patients who presented consecutively with CRC for the first time at our institution.

Results: The median age was 59 years (IQR 47 to 68), 119 (58.9%) were women, and 43 (21.3%) cases showed dMMR. The only clinicopathological characteristics associated with dMMR were the location in the right colon and the presence of a family history of cancer. In the multivariate analysis, only the presence of the tumor in the right colon was associated with dMMR (OR = 5.823, 95%-C.I. = 2.653-12.784, p < .001).

Conclusion: The 21.3% of the cases demonstrated a dMMR and the only clinical-pathological characteristic associated with dMMR was location in the right colon.
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http://dx.doi.org/10.1007/s12029-018-0132-1DOI Listing
September 2018

Comparison of 3 Ways of Dissecting the Pancreatoduodenectomy Specimen and Their Impact in the Lymph Node Count and the Lymph Node Metastatic Ratio.

Int J Surg Pathol 2018 Dec 6;26(8):707-713. Epub 2018 Jun 6.

2 Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.

Background: Lymph node metastasis (LNM) is a strong prognostic factor in the cancer of the pancreatobiliary tree, but it is influenced by the number of lymph nodes (LNs). The lymph node ratio (LNR) is considered a more reliable factor than the number of LNM. The aim was to examine the LN retrieval and the LNR of 3 pathologic work-up strategies.

Methods: Pancreaticoduodenectomies (n = 165) were analyzed comparing 3 pathological dissection techniques, classified as "control," "Verbeke method," and "Adsay method" groups.

Results: The mean of the dissected LNs and the number of cases with >20 LNs were superior in the Adsay method group, compared with the other groups ( P < .001). The LNR was different between the Adsay and Verbeke groups (0.144 vs 0.069, P = .032). The median of the 3 positive LNs was associated with decreased survival compared with an absence of LNM (3-year specific survival of 48% vs 22%, P = .011). In the multivariate analysis, LNM (hazard ratio = 6.148, 95% confidence interval = 2.02-8.1, P = .042) and the evaluation of >15 LNs (hazard ratio = 12.52, 95% confidence interval = 5.51-21.01, P = .001) were independent predictors of survival.

Conclusion: The Adsay technique for LN retrieval was associated with a better LN count, more cases with LNM, and an LNR >0.1.
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http://dx.doi.org/10.1177/1066896918780343DOI Listing
December 2018

Gastrointestinal Stromal Tumors Risk of Recurrence Stratification by Tumor Volume is a Best Predictor Compared with Risk Based on Mitosis and Tumor Size.

J Gastrointest Cancer 2019 Sep;50(3):513-518

Surgical Oncology, Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.

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.
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http://dx.doi.org/10.1007/s12029-018-0115-2DOI Listing
September 2019

Colorectal lymphoma in Mexico: clinico-pathological and survival analysis.

J Gastrointest Oncol 2018 Feb;9(1):90-95

Surgical Oncology, Hospital Ángeles Tijuana, Tijuana, Baja California Norte, Mexico.

Background: Primary colorectal lymphomas (PCLs) are very rare. We analyze a series of PCL to establish an approximate frequency of the disease and their clinico-pathological characteristics.

Methods: A retrospective cross-sectional study in a third-level hospital from 2006-2016. Clinico-pathologic features of 18 cases are presented.

Results: PCL corresponded to 1.5% of malignant colorectal neoplasms. Ten cases presented in men, the median age was 57 years, diffuse large B-cell lymphoma (DLBCL) was the most common subtype (55.6%), 55.6% presented in cecum, 83.4% as unique polypoid tumor and the median size was 52.5 mm. The most prevalent presentation symptom was abdominal pain (61.1%). Six cases (33%) received initial surgery followed by chemotherapy, 7 cases (39%) received only chemotherapy, 2 cases received only surgery and 3 cases no-treatment. The 2-year disease specific survival was 62.7%. The only factors associated with improved survival in univariate analysis were use of surgery followed by chemotherapy (P=0.043) and HIV (P=0.043). On multivariate analysis none factor was an independent risk factor for decreased survival.

Conclusions: The improved overall survival rates in our series emphasize the importance of surgery followed systemic therapy in the treatment of this disease.
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http://dx.doi.org/10.21037/jgo.2017.10.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848046PMC
February 2018

Gastric cancer in Latin America.

Scand J Gastroenterol 2018 Feb 23;53(2):124-129. Epub 2017 Dec 23.

f Laboratorio de Investigación Traslacional en Cáncer y Terapia Celular , Centro Médico Siglo XXI, IMSS , Ciudad de México , México.

Every year, cancer affects more than one million Latin Americans. The increasing incidence of cancer could be secondary to an aging population, westernization of life style, and urbanization. LA has among the highest incidence rates of gastric cancer, compared to other countries. In this review, different studies on gastric cancer and its relation with risks factors, such as infections, diet and life styles typical of LA, besides the different molecular alterations of that specific population (mainly at a genetic polymorphism level) are analyzed. An exhaustive research was made in PubMed, MEDLINE and Embase of the most relevant studies conducted in the last 27 years (1990-2017) in LA.
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http://dx.doi.org/10.1080/00365521.2017.1417473DOI Listing
February 2018