Predictive factors of lymphatic metastasis and evaluation of the Japanese treatment guidelines for endoscopic resection of early gastric cancer in a high-volume center in Perú.

Purpose: This study aimed to identify the predictive factors of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) and to evaluate the applicability of the Japanese treatment guidelines for endoscopic resection in the western population. Methods: Five hundred-one patients with pathological diagnoses of EGC were included. Univariate and multivariate analyses were conducted to identify the predictive factors of LNM. EGC patients were distributed according to the indications for endoscopic resection of the Eastern guidelines. The incidence of LNM was evaluated in each group. Results: From 501 patients with EGC, 96 (19.2%) presented LNM. In 279 patients with tumors with submucosal infiltration (T1b), 83 (30%) patients had LNM. Among 219 patients who presented tumors > 3 cm, 63 (29%) patients had LNM. Thirty-one percent of patients with ulcerated tumors presented LMN (33 out of 105). In 76 patients and 24 patients with lymphovascular and perineural invasion, the percentage of LMN was 84% and 87%, respectively. In the multivariate analysis, a tumor diameter >3 cm, submucosal invasion, lymphovascular, and perineural invasion were independent predictors of LMN in EGC. No patient with differentiated, non-ulcerated mucosal tumors presented LNM regardless of tumor size. Three of 17 patients (18%) with differentiated, ulcerated mucosal tumors and ≤ 3 cm presented LNM. No LNM was evidenced in patients with undifferentiated mucosal tumors and ≤ 2 cm. Conclusions: The presence of LNM in Western EGC patients was independently related to larger tumors (>3 cm), submucosal invasion, lymphovascular and perineural invasion. The Japanese absolute indications for EMR are safe in the Western population. Likewise, Western patients with differentiated, non-ulcerated mucosal tumors, and larger than 2 cm are susceptible to endoscopic resection. Patients with undifferentiated mucosal tumors smaller than 2 cm presented encouraging results and ESD could be recommended only for selected cases.

GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms.

Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.

Notch Signaling Promotes Mature T-Cell Lymphomagenesis.

Peripheral T-cell lymphomas (PTCL) are agressive lymphomas that develop from mature T cells. The most common PTCLs are genetically, molecularly, and clinically diverse and are generally associated with dismal outcomes. While Notch signaling plays a critically important role in both the development of immature T cells and their malignant transformation, its role in PTCL is poorly understood, despite the increasingly appreciated function of Notch in regulating the proliferation and differentiation of mature T cells. Here, we demonstrate that Notch receptors and their Delta-like family ligands (DLL1/DLL4) play a pathogenic role in PTCL. Notch1 activation was observed in common PTCL subtypes, including PTCL-not otherwise specified (NOS). In a large cohort of PTCL-NOS biopsies, Notch1 activation was significantly associated with surrogate markers of proliferation. Complementary genetically engineered mouse models and spontaneous PTCL models were used to functionally examine the role of Notch signaling, and Notch1/Notch2 blockade and pan-Notch blockade using dominant-negative MAML significantly impaired the proliferation of malignant T cells and PTCL progression in these models. Treatment with DLL1/DLL4 blocking antibodies established that Notch signaling is ligand-dependent. Together, these findings reveal a role for ligand-dependent Notch signaling in driving peripheral T-cell lymphomagenesis. SIGNIFICANCE: This work demonstrates that ligand-dependent Notch activation promotes the growth and proliferation of mature T-cell lymphomas, providing new therapeutic strategies for this group of aggressive lymphomas.

Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru; however, there are no prospective trials for adjuvant chemotherapy in GC after curative gastrectomy in this country. The objective of this study was to evaluate the effectiveness of adjuvant chemotherapy in stage II-III gastric cancer patients who underwent D2 gastrectomy. Methods: We included patients with stage II-III gastric cancer who underwent radical gastrectomy and D2 dissection between 2014 and 2016 at our institution. Patients received 3-week cycles of capecitabine (1,000 mg/m2 twice daily on days 1-14) plus oxaliplatin (130 mg/m2 on day 1) for 6 months. Survival curves were estimated with the Kaplan-Meier method, and the Cox proportional hazards model was used to identify prognostic factors for survival. Results: In total, 173 patients were included: 100 (57.8%) patients received adjuvant chemotherapy and surgery (AChS) and 73 (42.2%) surgery alone (SA). Three-year disease-free survival (DFS) was higher in the AChS groups (69%) than in the SA group (52.6%) (p = 0.034). Regarding overall survival (OS), 31 patients (31%) died in the AChS group compared with 34 (46.6%) in the SA group (p = 0.027). In the multivariate analysis, adjuvant chemotherapy was an independent prognostic factor for DFS (HR = 0.60; 95% CI = 0.37-0.97; p = 0.036) and OS (HR = 0.58; 95% CI = 0.36-0.95; p = 0.029). ACh showed consistent benefit in DFS and OS for patients with albumin >3.5 g/dL, lymphovascular and perineural invasion, pT4, pN2-3, pathologic stage (PS) IIIA and IIIB and lymph node ratio (LNR) > 13.1. Conclusion: These data suggest that adjuvant capecitabine and oxaliplatin reduce the recurrence and mortality in patients with stage II-III gastric cancer who underwent D2 gastrectomy. PS IIIA and IIIB and LNR > 13.1 benefited more from receiving adjuvant chemotherapy and poorly cohesive gastric carcinoma did not significantly reduce the rates of survival.

The relationship between tumour infiltrating lymphocytes, Epstein-Barr virus and Helicobacter pylori infection in gastric cancer.

Objective: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections have been extensively recognised as gastric cancer (GC) triggers, and recent publications suggest they could behave as predictive markers for immune-modulating therapies. Tumour-infiltrating lymphocytes (TILs) have also been identified as a predictive biomarker for immunotherapy in different malignancies. This study aimed to investigate the association between EBV and HP infection with TIL levels in GC. Methods: TIL evaluation in haematoxylin-eosin was performed by a pathologist and density of CD3, CD8 and CD163 positive (immunohistochemistry staining) immune cells was calculated with the use of digital pathology software. EBV infection was detected by in situ hybridisation (ISH) and by quantitative polymerase chain reaction (qPCR). Methylation status of EBV-related genes was detected by PCR and a methylome analysis was performed by the Illumina Infinium MethylationEPIC BeadChip. HP status was detected by qPCR. Results: We included 98 resected GC Peruvian cases in our evaluation. Median TIL percentage was 30. The proportion of EBV+ detected by ISH was 24.1%, of EBV+ detected by qPCR was 41.8%, while 70% showed methylation of EBV-related genes, and 58.21% of cases were HP+. Younger age (p = 0.024), early stages (p = 0.001), HP+ (p = 0.036) and low CD8 density (p = 0.046) were associated with longer overall survival (OS). High TIL level was associated with intestinal subtype (p < 0.001), with grade 2 (p < 0.001), with EBV qPCR+ (p = 0.001), and with methylation of EBV-related genes (p = 0.007). Cases with high TIL level and cases that are EBV positive share eight genes with similarly methylated status in the metabolomic analysis. High CD8 density was associated with EBV PCR+ (p = 0.012) and HP- (0.005). Conclusion: Lower CD8 density and HP+ predict longer OS. High TIL level is associated with EBV+ and methylation of EBV-related genes, while lower CD8 density is associated with HP+ GC.

Survival after curative pancreaticoduodenectomy for ampullary adenocarcinoma in a South American population: A retrospective cohort study.

BACKGROUND: Ampullary adenocarcinoma (AAC) is a rare neoplasm that accounts for only 0.2% of all gastrointestinal cancers. Its incidence rate is lower than 6 cases per million people. Different prognostic factors have been described for AAC and are associated with a wide range of survival rates. However, these studies have been exclusively conducted in patients originating from Asian, European, and North American countries. AIM: To evaluate the histopathologic predictors of overall survival (OS) in South American patients with AAC treated with curative pancreaticoduodenectomy (PD). METHODS: We analyzed retrospective data from 83 AAC patients who underwent curative (R0) PD at the National Cancer Institute of Peru between January 2010 and October 2020 to identify histopathologic predictors of OS. RESULTS: Sixty-nine percent of patients had developed intestinal-type AAC (69%), 23% had pancreatobiliary-type AAC, and 8% had other subtypes. Forty-one percent of patients were classified as Stage I, according to the AJCC 8th Edition. Recurrence occurred primarily in the liver (n = 8), peritoneum (n = 4), and lung (n = 4). Statistical analyses indicated that T3 tumour stage [hazard ratio (HR) of 6.4, 95% confidence interval (CI) of 2.5-16.3, P < 0.001], lymph node metastasis (HR: 4.5, 95%CI: 1.8-11.3, P = 0.001), and pancreatobiliary type (HR: 2.7, 95%CI: 1.2-6.2, P = 0.025) were independent predictors of OS. CONCLUSION: Extended tumour stage (T3), pancreatobiliary type, and positive lymph node metastasis represent independent predictors of a lower OS rate in South American AAC patients who underwent curative PD.

Metallomic profile in non-cirrhotic hepatocellular carcinoma supports a phenomenon of metal metabolism adaptation in tumor cells.

We have previously described a form of hepatocellular carcinoma (HCC) in non-cirrhotic liver (HCC-NC) developed by Peruvian patients. We analyzed the metallomic profile in hepatic tissues from two independent cohorts exhibiting HCC-NC. Clinical, histopathological data, and HCC and non-tumoral liver (NTL) samples of 38 Peruvian and 38 French HCC-NC patients, were studied. Twelve metals were quantified using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Associations between metals and survival were assessed. Our data showed significant differences between cohorts. Mean ages were 40.6 ± 20, 67.5 ± 9 years old for Peruvians and French, respectively. Fifty percent of the Peruvian patients were positive for the HBsAg, versus 3% in French patients. Mn, Cu, Zn, As, Se, Rb, Mo, Cd, Sn metal concentrations were higher in NTL of Peruvians. Importantly, metal concentrations were lower in HCC areas compared to NTL tissues in both cohorts, except for Cu for which mean concentration was higher in HCC (p < 0.05). Se concentration in HCC was associated with extended survival only in Peruvians. Our data, obtained in Peruvian and French HCC-NC cohorts, highlights similarity in the metallomic profile of HCC compared to NTL during the hepatic tumorigenesis in these specific groups of patients.

Detection of Helicobacter pylori in gastric cancer tissue through histopathology, immunohistochemistry and real-time reverse transcription-PCR.

Aim:Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results:H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.

Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies.

Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.

Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy: a randomized non-inferiority study.

INTRODUCTION: Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation. METHODS: We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO2) cryotherapy (referent), single-freeze CO2 cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation. Subjects were 130 women scheduled for hysterectomy for indications other than cervical pathology, and thus with healthy cervical tissue available for histological evaluation of depth of necrosis post-surgery. The null hypothesis was rejected (ie, conclude non-inferiority) if the upper bound of the 90% confidence interval (90% CI) for the difference in mean depth of necrosis (referent minus each experimental method) was <1.14 mm. Patient pain during treatment was reported on a scale of 0 (no pain) to 10 (worst pain). RESULTS: A total of 133 patients were enrolled in the study. The slides from three women were deemed unreadable. One patient was excluded because her hysterectomy was postponed for reasons unrelated to the study, and two patients were excluded because treatment application did not follow the established protocol. For the remaining 127 women, mean depth of necrosis for double-freeze CO2 (referent) was 6.0±1.6 mm. Differences between this and other methods were: single-freeze CO2 = 0.4 mm (90% CI -0.4 to 1.2 mm), double-freeze CryoPen= 0.7 mm (90% CI 0.04 to 1.4 mm), single-freeze CryoPen= 0.5 mm (90% CI -0.2 to 1.2 mm), and thermoablation = 2.6 mm (90% CI 2.0 to 3.1 mm). Mean pain levels were 2.2±1.0 (double-freeze CO2 cryotherapy), 1.8±0.8 (single-freeze CO2 cryotherapy), 2.5±1.4 (double-freeze CryoPen), 2.6±1.4 (single-freeze CryoPen), and 4.1±2.3 (thermoablation). DISCUSSION: Compared with the referent, non-inferiority could not be concluded for other methods. Mean pain scores were low for all treatments. Depth of necrosis is a surrogate for treatment efficacy, but a randomized clinical trial is necessary to establish true cure rates.

Prostate cancer mortality rates in Peru and its geographical regions.

OBJECTIVE: To evaluate the mortality rates for prostate cancer according to geographical areas in Peru between 2005 and 2014. MATERIALS AND METHODS: Information was extracted from the Deceased Registry of the Peruvian Ministry of Health. We analysed age-standardised mortality rates (world population) per 100 000 men. Spatial autocorrelation was determined according to the Moran Index. In addition, we used Cluster Map to explore relations between regions. RESULTS: Mortality rates increased from 20.9 (2005-2009) to 24.1 (2010-2014) per 100 000 men, an increase of 15.2%. According to regions, during the period 2010-2014, the coast had the highest mortality rate (28.9 per 100 000), whilst the rainforest had the lowest (7.43 per 100 000). In addition, there was an increase in mortality in the coast and a decline in the rainforest over the period 2005-2014. The provinces with the highest mortality were Piura, Lambayeque, La Libertad, Callao, Lima, Ica, and Arequipa. Moreover, these provinces (except Arequipa) showed increasing trends during the years under study. The provinces with the lowest observed prostate cancer mortality rates were Loreto, Ucayali, and Madre de Dios. This study showed positive spatial autocorrelation (Moran's I: 0.30, P = 0.01). CONCLUSION: Mortality rates from prostate cancer in Peru continue to increase. These rates are higher in the coastal region compared to those in the highlands or rainforest.

Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America.

We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.

[Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru]. / Tuberculosis que imita cáncer: casos derivados al Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú.

Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.

La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.

Tuberculosis que imita cáncer: casos derivados al Instituto Nacional de Enfermedades Neoplásicas, Lima-Perú / Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru

RESUMEN La tuberculosis (TB) es un importante problema de salud pública que debido a la variabilidad clínica de su presentación, puede confundirse con una malignidad. El objetivo del estudio fue identificar las características clínico radiológicas y describir la metodología que permitió llegar al diagnóstico de TB en pacientes derivados con presunción diagnóstica de cáncer al Instituto Nacional de Enfermedades Neoplásicas (INEN) entre 2014 y 2016. Se incluyeron 170 pacientes (52,4 % hombres) con edad promedio de 41,1 años, 18 % presentaron antecedentes de contacto con TB y un 5,9 % tuvo previamente la enfermedad. La TB fue pulmonar en 22,4 % y extrapulmonar en 77,7 % de los pacientes. Los síntomas más frecuentes fueron respiratorios, tumoración, pérdida de peso y neurológicos. Los diagnósticos oncológicos descartados con mayor frecuencia fueron linfoma, cáncer pulmonar y cerebral. Las lesiones que sugerían una neoplasia indicaron un estadio clínico avanzado en el 63,5 %. Se concluye que los síntomas e imágenes asociados a TB pueden confundirse con neoplasias malignas.

ABSTRACT Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

OBJECTIVE: To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting. METHODS: One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically. RESULTS: The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth. CONCLUSIONS: Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.

Cáncer colorrectal en los jóvenes: factores pronósticos y características clínico patológicas en un instituto del cáncer de Perú.

OBJECTIVE: To determine clinicopathological features and prognostic factors among young colorectal cancer (CRC) patients in a Peruvian Cancer Institute. METHODS: Data of patients 40 years or younger, admitted between January 2005 and December 2010, were analyzed. RESULTS: During the study period, 196 young patients with CRC were admitted. The tumor was located in the rectum, left colon and right colon in 45.9%, 28.6% and 25.5% of cases. Family history of CRC was found in 13.2% and an autosomal pattern of inheritance, in 8.6% of the cases. The most common symptoms were pain (67.9%) and bleeding (67.3%). The majority (63.1%) of colon cancer cases and more than a third (34.4%) of rectal cancer cases were diagnosed in stage III or IV. The histologic type was tubular, mucinous and signet ring cell adenocarcinoma in 73.5%, 14.8% and 8.6%, respectively. The depth of invasion was T3 in 21.4% and T4 in 53%. Nodal involvement was detected in 44.5%. Five-year overall survival (OS) was 44.3%. In the multivariate analysis, only the stage resulted an independent prognostic factor for survival. CONCLUSIONS: CRC in Peruvian young patients is mostly sporadic. It presents more often in the distal colon or rectum and at advanced stages of the disease. Mucinous and signet ring cell carcinoma were requent histological types. Five-year OS stage by stage is similar to that reported in the literature for older patients. Stage was the only independent prognostic factor for survival.

Cáncer colorrectal en los jóvenes: factores pronósticos y características clínico patológicas en un instituto del cáncer de Perú / Colorectal cancer in the young: clinicopathologic features and prognostic factors from a cancer institute in Peru

To determine clinicopathological features and prognostic factors among young colorectal cancer (CRC) patients in a Peruvian Cancer Institute. Methods: Data of patients 40 years or younger, admitted between January 2005 and December 2010, were analyzed. Results: During the study period, 196 young patients with CRC were admitted. The tumor was located in the rectum, left colon and right colon in 45.9%, 28.6% and 25.5% of cases. Family history of CRC was found in 13.2% and an autosomal pattern of inheritance, in 8.6% of the cases. The most common symptoms were pain (67.9%) and bleeding (67.3%). The majority (63.1%) of colon cancer cases and more than a third (34.4%) of rectal cancer cases were diagnosed in stage III or IV. The histologic type was tubular, mucinous and signet ring cell adenocarcinoma in 73.5%, 14.8% and 8.6%, respectively. The depth of invasion was T3 in 21.4% and T4 in 53%. Nodal involvement was detected in 44.5%. Five-year overall survival (OS) was 44.3%. In the multivariate analysis, only the stage resulted an independent prognostic factor for survival. Conclusions: CRC in Peruvian young patients is mostly sporadic. It presents more often in the distal colon or rectum and at advanced stages of the disease. Mucinous and signet ring cell carcinoma were frequent histological types. Five-year OS stage by stage is similar to that reported in the literature for older patients. Stage was the only independent prognostic factor for survival...

Determinar las características clínicopatológicas y factores relacionados con el pronóstico del cáncer colorrectal (CCR) en los pacientes jóvenes del Instituto Nacional de Enfermedades Neoplásicas (INEN). Material y métodos: Se analizaron retrospectivamente los datos de los pacientes de 40 o menos años admitidos entre enero del 2005 y diciembre del 2010. Resultados: Se incluyeron 196 pacientes. La localización correspondió al recto, colon izquierdo y colon derecho en 45,9%, 28,6% y 25,5%. En 13,2% hubo antecedentes familiares de CCR y en 8.6%, un patrón de herencia autosómico dominante. Los síntomas más frecuentes fueron dolor (67,9%) y sangrado (67,3%). El 63,1% de los casos de cáncer de colon y el 34,4% de los casos de cáncer de recto, se diagnosticaron en estadio clínico (EC) III o IV. El tipo histológico correspondió a adenocarcinoma tubular, mucinoso y de células en anillo de sello en 73,5%, 14,8% y 8,6%, respectivamente. La profundidad de la invasión fue de T3 en 21,4% y de T4 en 53%. En 44,5% de los casos hubo compromiso ganglionar. La sobrevida global (SG) a 5 años fue de 44,3%. En el análisis multivariado, el estadio resultó ser un factor pronóstico independiente. Conclusiones: El CCR en jóvenes es en su mayoría esporádico, se presenta con mayor frecuencia en el colon distal o recto y en estadios avanzados. El carcinoma mucinoso y de células en anillo de sello fueron tipos histológicos frecuentes. La SG comparada por estadios es similar a la reportada en la literatura. El EC fue el único factor pronóstico independiente para sobrevida...

Mutational profile of KIT and PDGFRA genes in gastrointestinal stromal tumors in Peruvian samples.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms usually caused by somatic mutations in the genes KIT (c-kit) or PDGFRA. Mutation characterization has become an important exam for GIST patients because it is useful in predicting the response to the inhibitors of receptor tyrosine kinase (RTK). OBJECTIVES: The aim of this study was to determine the frequency of KIT and PDGFRA mutations in 25 GIST samples collected over two years at two national reference hospitals in Peru. There were 21 samples collected from the Instituto Nacional de Enfermedades Neoplásicas (INEN, national cancer center) and 4 samples collected from Hospital A. Loayza. METHODS AND MATERIALS: In this retrospective study, we performed polymerase chain reaction (PCR) amplification and deoxyribonucleic acid (DNA) sequencing of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in 20 FFPE (formalin-fixed, paraffin-embedded) and 5 frozen GIST samples. RESULTS: We report 21 mutations, including deletions, duplications, and missense, no mutations in 2 samples, and 2 samples with no useful DNA for further analysis. Eighty-six percent of these mutations were located in exon 11 of KIT, and 14 % were located in exon 18 of PDGFRA. CONCLUSIONS: Our study identified mutations in 21 out of 25 GIST samples from 2 referential national hospitals in Peru, and the mutation proportion follows a global tendency observed from previous studies (i.e., the majority of samples presented KIT mutations followed by a minor percentage of PDGFRA mutations). This study presents the first mutation data of the KIT and PDGFRA genes from Peruvian individuals with GIST.

Identificación de una deleción causante de tumor del estroma gastrointestinal (Gist) por el análisis de los genes KIT y PDGFRA / Identification of a causative deletion of gastrointestinal stromal tumor (gist) by the analysis of the KIT and PDGFRA genes

Optimizar la detección de mutaciones en los genes KIT y PDGFRA en una muestra de tumor del estroma gastrointestinal (GIST). Material y Métodos: Se analizó una muestra de tumor GIST fijada y embebida en parafina. Mediante la técnica de reacción en cadena de la polimerasa (PCR) se amplificaron los exones 9, 11, 13 y 17 del gen KIT y los exones 12 y 18 del gen PDGFR que contienen las mutaciones causales de GIST. Se confirmó la amplificación mediante electroforesis en gel de agarosa al 2%. Los fragmentos amplificados, fueron purificados y secuenciados en un analizador genético. Se detectó una sobreposición de bases propio de una deleción por lo que se tuvo que clonar los productos del exón 11 para identificar el alelo mutado. Resultados: Se determinó la presencia de una mutación patogénica en el exón 11 del gen KIT. Dicha mutación es una deleción de 15 pares de bases que genera la pérdida de 5 aminoácidos en el receptor tirosina kinasa KIT. Se encontraron polimorfismos neutrales en los exones 11 del gen KIT y en el exón 18 del gen PDGFRA. Conclusión: El análisis molecular mediante secuenciación automática, permitió identificar una mutación en el gen KIT en una muestra de tumor GIST. Esta técnica puede ser aplicada para caracterizar las mutaciones genéticas de casos peruanos de GIST y así poder establecer un tratamiento adecuado según su perfil mutacional...

Objective: To optimize the detection of mutations in the genes KIT and PDGFRA in a sample of gastrointestinal stromal tumor (GIST). Material and Methods: We analyzed a GIST tumor sample fixed and embedded in paraffin. Using the technique of the polymerase chain reaction (PCR) we amplified exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 PDGFR gene which contain tha causal mutations of GIST. PCR amplification was confirmed by gel electrophoresis on 2% agarose. The amplified fragments were purified and cloned for subsequent sequencing. An overlap of baeses, characteristic of a deletion was detected, so we had to clone the exon 11 products to identify mutated allele. Results: We determined the presence of a pathogenic mutation in exon 11 of KIT gene. The mutation is a deletion of 15 base pairs and generates a loss of 5 amino acids in the KIT receptor tyrosine kinase. Neutral polymorphisms were also found in exon 11 of KIT gene and exon 18 of PDGFRA gene. Conclusion: Molecular analysis by automatic sequencing identified a mutation in the KIT gene in a tumor sample GIST. This technique can be applied to characterize genetic mutations Peruvian cases of GIST and thus establish adequate treatment by mutational profile...

Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru.

It is well known that extranodal NK/T-cell lymphoma (NK/TCL) nasal type clusters in Asian countries. A large series of 78 cases of nasal NK/TCL from Peru is analyzed in the present study. Two histologic groups 1 (monomorphic) and 2 (polymorphic), were segregated according to the proportion of large cells (above and below 30%, respectively). Catalyzed signal amplification technique was performed for enhancement of immunohistochemistry reactivities. Epstein-Barr virus (EBV) sequences and types were investigated using polymerase chain reaction. Clinical characteristics, stage, outcome, and response to treatment were evaluated in both groups. Fourteen cases (18%) and 64 cases (82%) corresponded to groups 1 and 2, respectively. Except for nasal obstruction, more common in group 2, all other symptoms were similar in both groups. Local extension and staging were also comparable. Both groups showed CD3c+ CD2+ CD56+ CD3s- CD20- immunophenotype. All cases were positive for EBV. In this series type-2 EBV was found more frequent than type-1 EBV, contrarily to that observed in Asian series. However, about one-third of cases simultaneously harbored both viral types. Both groups received an average of 50-Gy dose of radiation therapy (RT), with or without chemotherapy. Complete therapeutic response was achieved in 89% of group 1 and in 74% of group 2, but this difference was not statistically significant. There were no significant differences between the groups regarding disease-free survival, failure-free survival, relapse, and overall survival. The overall survival, in both groups, was longer for patients treated with RT alone compared with those treated with combined RT therapy and chemotherapy. The present study has shown that dividing nasal NK/TCL in monomorphic and polymorphic variants, according to frequency of large cells, does not correlate with clinical and prognostic factors.