Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.

BACKGROUND: Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy. METHODS: 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples. RESULTS: Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort. CONCLUSION: The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.

THE CHANGING TREND OF MORTALITY CAUSED BY GASTROINTESTINAL CANCERS IN IRAN DURING THE YEARS 2006-2010.

BACKGROUND: Cancers are one of the most important causes of death in the world. According to their high incidence and mortality, gastrointestinal cancers have particular importance among other cancers. OBJECTIVE: Therefore, this study was conducted to investigate the mortality change trends of gastrointestinal cancers in Iran. METHODS: This study was performed by analyzing the reported mortality data in 29 provinces of Iran in 2006-2010. Mortality trend of gastrointestinal cancers was drawn for both sexes in the study years and disaggregated by age groups and their frequency distribution. The WinPepi software was used for analysis. RESULTS: In the years 2006-2010, the mortality rate of, gastric, colorectal, liver and pancreatic cancers, has significantly increased. Totally, gastrointestinal mortality is higher in men than women. Also, the results showed that by increasing age, death from these cancers also increased. CONCLUSION: The most important causes of death from gastrointestinal cancers were gastric, liver and colorectal cancers in Iran and because of their increasing trend in the country, performing preventive interventions for the cancers' risk factors is necessary.

A mudança da tendência de mortalidade causada por câncer gastrointestinal no Irã durante os anos 2006-2010 / The changing trend of mortality caused by gastrointestinal cancers in iran during the years 2006-2010

ABSTRACT BACKGROUND: Cancers are one of the most important causes of death in the world. According to their high incidence and mortality, gastrointestinal cancers have particular importance among other cancers. OBJECTIVE: Therefore, this study was conducted to investigate the mortality change trends of gastrointestinal cancers in Iran. METHODS: This study was performed by analyzing the reported mortality data in 29 provinces of Iran in 2006-2010. Mortality trend of gastrointestinal cancers was drawn for both sexes in the study years and disaggregated by age groups and their frequency distribution. The WinPepi software was used for analysis. RESULTS: In the years 2006-2010, the mortality rate of, gastric, colorectal, liver and pancreatic cancers, has significantly increased. Totally, gastrointestinal mortality is higher in men than women. Also, the results showed that by increasing age, death from these cancers also increased. CONCLUSION: The most important causes of death from gastrointestinal cancers were gastric, liver and colorectal cancers in Iran and because of their increasing trend in the country, performing preventive interventions for the cancers' risk factors is necessary.

RESUMO CONTEXTO: O câncer é uma das causas mais importantes de morte no mundo. De acordo com a sua alta incidência e mortalidade, o câncer gastrointestinal tem particular importância entre outros tipos de neoplasias. OBJETIVO: Este estudo foi conduzido para investigar as tendências de mudança de mortalidade de câncer gastrointestinal no Irã. MÉTODOS: Foi realizada pesquisa analisando-se os dados de mortalidade relatados em 29 províncias do Irã entre 2006-2010. A tendência de mortalidade de câncer gastrointestinal foi delineada para ambos os sexos nos anos de estudo e desagregadas por grupos etários em sua distribuição de frequência. O software WinPepi foi usado para análise. RESULTADOS: Nos anos 2006-2010, a taxa de mortalidade por câncer gástrico, colorretal, de fígado e pancreático aumentou significativamente. A mortalidade por câncer gastrointestinal é maior nos homens do que nas mulheres e, além disso, os resultados mostraram que com o aumentar a idade, a morte causada por estes cânceres também aumentou. CONCLUSÃO: As causas mais importantes da morte entre cânceres de origem gastrointestinal no Irã foram o gástrico, o hepático e o colorretal e devido a sua tendência crescente no país, a realização de intervenções preventivas para os fatores de risco é necessária.

Inflammatory and nutritional statuses of patients submitted to resection of gastrointestinal tumors.

OBJECTIVE: to evaluate the association between the nutritional and the inflammatory statuses of patients with cancer of the gastrointestinal tract undergoing surgical resection and to identify predictors of mortality in these patients. METHODS: we conducted a prospective study of 41 patients with gastrointestinal tract cancer submitted to surgery between October 2012 and December 2014. We evaluated the nutritional status by subjective and objective methods. We assessed the inflammatory response and prognosis using the modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), Onodera Prognostic Nutritional Index (mPNI), Inflammatory-Nutritional Index (INI) and C-Reactive Protein/Albumin ratio (mPINI). RESULTS: half of the patients were malnourished and 27% were at nutritional risk. There was a positive association between the percentage of weight loss (%WL) and the markers NLR (p=0.047), mPINI (p=0.014) and INI (p=0.015). Serum albumin levels (p=0.015), INI (p=0.026) and mPINI (p=0.026) were significantly associated with the PG-SGA categories. On multivariate analysis, albumin was the only inflammatory marker independently related to death (p=0.004). CONCLUSION: inflammatory markers were significantly associated with malnutrition, demonstrating that the higher the inflammatory response, the worse the PG-SGA (B and C) scores and the higher the %WL in these patients. However, further studies aimed at improving surgical outcomes and determining the role of these markers as predictors of mortality are required.

Inflammatory and nutritional statuses of patients submitted to resection of gastrointestinal tumors / Estado inflamatório e nutricional em pacientes submetidos à ressecção cirúrgica de tumores do trato gastrointestinal

ABSTRACT Objective: to evaluate the association between the nutritional and the inflammatory statuses of patients with cancer of the gastrointestinal tract undergoing surgical resection and to identify predictors of mortality in these patients. Methods: we conducted a prospective study of 41 patients with gastrointestinal tract cancer submitted to surgery between October 2012 and December 2014. We evaluated the nutritional status by subjective and objective methods. We assessed the inflammatory response and prognosis using the modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), Onodera Prognostic Nutritional Index (mPNI), Inflammatory-Nutritional Index (INI) and C-Reactive Protein/Albumin ratio (mPINI). Results: half of the patients were malnourished and 27% were at nutritional risk. There was a positive association between the percentage of weight loss (%WL) and the markers NLR (p=0.047), mPINI (p=0.014) and INI (p=0.015). Serum albumin levels (p=0.015), INI (p=0.026) and mPINI (p=0.026) were significantly associated with the PG-SGA categories. On multivariate analysis, albumin was the only inflammatory marker independently related to death (p=0.004). Conclusion: inflammatory markers were significantly associated with malnutrition, demonstrating that the higher the inflammatory response, the worse the PG-SGA (B and C) scores and the higher the %WL in these patients. However, further studies aimed at improving surgical outcomes and determining the role of these markers as predictors of mortality are required.

RESUMO Objetivo: avaliar a associação entre o estado nutricional e inflamatório em pacientes com câncer do trato gastrointestinal submetidos à ressecção cirúrgica e identificar variáveis preditoras de mortalidade nestes pacientes. Métodos: estudo prospectivo de 41 pacientes com câncer do trato gastrointestinal submetidos à cirurgia entre outubro de 2012 e dezembro de 2014. O estado nutricional foi avaliado por métodos subjetivos e objetivos. A resposta inflamatória e o prognóstico foram avaliados através do Escore Prognóstico de Glasgow modificado (mGPS), razão Neutrófilo/Linfócito (NLR), Índice Nutricional Prognóstico de Onodera (mPNI), Índice Inflamatório Nutricional (INI) e razão Proteína C-reativa/Albumina (mPINI). Resultados: metade dos pacientes estava desnutrida e 27% apresentavam-se em risco nutricional. Associação positiva foi encontrada entre percentual de perda de peso (%PP) e os marcadores NLR (p=0,047), mPINI (p=0,014) e INI (p=0,015) e os níveis séricos de albumina (p=0,015), INI (p=0,026) e mPINI (p=0,026) se associaram significativamente às categorias da ASG-PPP. Na análise multivariada, a albumina foi o único marcador inflamatório independentemente relacionado ao óbito (p=0,004). Conclusão: marcadores inflamatórios foram significativamente associados com a desnutrição, demonstrando que quanto maior a resposta inflamatória, piores foram os escores da ASG-PPP (B e C) e maior o %PP nesses pacientes. No entanto, mais estudos, com o objetivo de melhorar resultados cirúrgicos e determinar o papel desses marcadores como preditores de mortalidade são necessários.

Cachexia Stage, Patient-Generated Subjective Global Assessment, Phase Angle, and Handgrip Strength in Patients with Gastrointestinal Cancer.

The aim of this study was to correlate patients with gastrointestinal cancer, classified according to different stages of cancer cachexia (SCC) as proposed by Fearon, with nutritional assessment tools such as PG-SGA, phase angle (PA), and handgrip strength. One hundred one patients with a mean age of 61.8 ± 12.8 yr, with 58.4% being men were included. 32.6% were malnourished according to the body mass index (BMI). A severe or moderate malnutrition had been diagnosed in 63.3% when assessed using the PG-SGA, 60.4% had decreased handgrip strength, and 57.4% had lower grades of PA. Among the patients in the study, 26% did not have cachexia, 11% had precachexia, 56% cachexia, and 8% refractory cachexia. The PG-SGA, PA, and handgrip strength were associated with cachexia (P ≤ 0.001). An increased risk of death was found in patients with cachexia [RR: 9.1; confidence interval (CI) 95%: 0.1-90.2, P = 0.039], refractory cachexia (RR: 69.4, CI 95%: 4.5-1073.8, P = 0.002), and increased serum C-reactive protein (CRP) levels (P < 0.001). In conclusion, most of the patients with digestive system cancer had cachexia or refractory cachexia in the first nutritional assessment. Nutritional risk, as determined by PG-SGA, was correlated with PA and handgrip strength. High CRP levels, cachexia, and refractory cachexia were prognostic factors for cancer patients.

Temporal trends and regional variations in gastrointestinal cancer mortality in Peru, 2005-2014 / Tendencia y variaciones regionales de la mortalidad por cáncer gastrointestinal en Perú, 2005-2014

Objective: To estimate and analyze the evolution of mortality rates of gastrointestinal (GI) cancer in Peru and its regions between 2005-2014. Material and methods: We performed a nationwide secondary analysis of Peru's Health Ministry registry of deaths during the period 2005-2014, with a focus on regional differences. Deaths registered with codes C15 to C25 (malignant neoplasms of digestive organs) from the ICD-10 were included. Calculation of age-standarized mortality rates and years of life lost (YLL) due to GI cancer per 100,000 habitants were also performed. Results: Data of 67,527 deaths from GI cancers was analyzed, 35,055 (51.91%) were women. In 2005, the number of GI cancer deaths was 6,484, for 2014, 7,532 cases were recorded. The GI cancer age-standarized mortality rates at the country level showed a decrease of 12.70% between 2005-2014. Stomach cancer presented the highest age-standarized mortality rate despite showing a downward trend in the last years, equal for gallbladder, liver and biliary tract, and esophagus cancer. Colorectal, small intestine and anus cancer show a progressive increase. In 2014, Callao (48.8), Huancavelica (48.5), La Libertad (39.6), Lambayeque (40.5) and Huanuco (38.9) had the highest rates. The three types of GI cancers with the highest rates of YLL in 2014 were stomach cancer (118.51), followed by liver and biliary tract cancer (58.68) and colorectal (44.86). Conclusion: GI cancer mortality in Peru is high and a priority issue in regions like Huancavelica, Huanuco, Callao, La Libertad and Lambayeque. Stomach cancer remains the most frequent GI cancer, but with a downward trend in the study period.

Objetivo: Estimar y analizar la evolución de las tasas de mortalidad de cáncer gastrointestinal (GI) en el Perú y sus regiones entre 2005-2014. Material y métodos: Se realizó un análisis secundario del registro de defunciones del Ministerio de Salud de Perú para el período 2005-2014 con los códigos C15 a C25 (neoplasias malignas de los órganos digestivos) de la versión 10 de la Clasificación Internacional de Enfermedades, además se calculó tasas de mortalidad ajustadas y años de vida perdidos (AVP) debido a cánceres GI por 100 000 habitantes. Resultados: Se analizaron datos de 67 527 muertes por cáncer GI, 35 055 (51,91%) eran mujeres. En 2005, el número de muertes fueron 6484; en 2014, hubo 7532 casos. Las tasas de mortalidad ajustadas a nivel nacional mostraron una disminución del 12,70% entre 2005-2014. El cáncer de estómago presentó la mayor tasa de mortalidad ajustada a pesar de mostrar una tendencia a la baja en los últimos años, igual para el cáncer de la vesícula biliar, del hígado y vías biliares y esófago. El cáncer colorrectal, de intestino delgado y de ano, mostraron tendencia al aumento. En 2014, Callao (48,8), Huancavelica (48,5), La Libertad (39,6), Lambayeque (40,5) y Huánuco (38,9) tuvieron las tasas más altas. Los tres tipos de cáncer GI con las tasas más altas de AVP en 2014 fueron el cáncer de estómago (118,51), cáncer de hígado y vías biliares (58,68) y colorrectal (44,86). Conclusión: La mortalidad por cáncer GI en Perú es alta, siendo un tema prioritario en regiones como Huancavelica, Huánuco, Callao, La Libertad y Lambayeque. El cáncer de estómago sigue siendo el cáncer GI más frecuente, pero con una tendencia descendente.

Prognostic factors in patients with malignant pleural effusion: Is it possible to predict mortality in patients with good performance status?

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of mortality only in patients with malignant pleural effusion (MPE) showing good performance status which required pleural palliative procedures. METHODS: All patients with MPE submitted to pleural palliative procedure were enrolled in a prospective study between 2013 and 2014. Patients with Eastern cooperative oncology group (ECOG) score zero, one, and two were considered with good performance status. The possible prognostic factors were tested for significance using the log-rank test (Kaplan-Meier method) and those with significance on univariate analysis were entered into a multivariable Cox model. RESULTS: A total of 64 patients were included in the analysis. Median follow-up time for surviving patients was 263 days. Median survival for the entire cohort was not reached yet. In the multivariate analysis, gastrointestinal primary site (P = 0.006), low albumin concentration in the pleural fluid (P = 0.017), and high serum NLR (P = 0.007) were associated with mortality. CONCLUSION: In our cohort of ECOG 0-2 patients with MPE submitted to pleural palliative procedures, gastrointestinal malignancy compared to other sites, low pleural fluid albumin and high NLR were significantly associated with mortality. The identification of these prognostic factors may assist the choice of the optimal palliative technique. J. Surg. Oncol. 2016;113:570-574. © 2016 Wiley Periodicals, Inc.

Temporal trends and regional variations in gastrointestinal cancer mortality in Peru, 2005-2014.

OBJECTIVE: To estimate and analyze the evolution of mortality rates of gastrointestinal (GI) cancer in Peru and its regions between 2005-2014. MATERIAL AND METHODS: We performed a nationwide secondary analysis of Peru's Health Ministry registry of deaths during the period 2005-2014, with a focus on regional differences. Deaths registered with codes C15 to C25 (malignant neoplasms of digestive organs) from the ICD-10 were included. Calculation of age-standarized mortality rates and years of life lost (YLL) due to GI cancer per 100,000 habitants were also performed. RESULTS: Data of 67,527 deaths from GI cancers was analyzed, 35,055 (51.91%) were women. In 2005, the number of GI cancer deaths was 6,484, for 2014, 7,532 cases were recorded. The GI cancer age-standarized mortality rates at the country level showed a decrease of 12.70% between 2005-2014. Stomach cancer presented the highest age-standarized mortality rate despite showing a downward trend in the last years, equal for gallbladder, liver and biliary tract, and esophagus cancer. Colorectal, small intestine and anus cancer show a progressive increase. In 2014, Callao (48.8), Huancavelica (48.5), La Libertad (39.6), Lambayeque (40.5) and Huanuco (38.9) had the highest rates. The three types of GI cancers with the highest rates of YLL in 2014 were stomach cancer (118.51), followed by liver and biliary tract cancer (58.68) and colorectal (44.86). CONCLUSION: GI cancer mortality in Peru is high and a priority issue in regions like Huancavelica, Huanuco, Callao, La Libertad and Lambayeque. Stomach cancer remains the most frequent GI cancer, but with a downward trend in the study period.

Patients with brain metastases derived from gastrointestinal cancer: clinical characteristics and prognostic factors.

PURPOSE: This study seeks to evaluate the natural history, outcome, and possible prognostic factors in patients with brain metastases derived from gastrointestinal cancers. METHODS: The clinical features, prognostic factors, and the effects of different treatment modalities on survival were retrospectively investigated in 103 patients with brain metastases derived from gastrointestinal cancers. RESULTS: The median time from diagnosis of primary tumor to brain metastasis was 22.00 months. The interval between diagnosis of primary tumor relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80 months. The median survival time after diagnosis of brain metastases was 4.10 months for all patients and 1.17 months for patients who received only steroids (36.9 %), 3.97 months for patients who only received whole-brain radiation therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis revealed that recursive partitioning analysis (RPA) class, extracranial metastasis, and chemotherapy were independent prognostic factors. Brain metastasis derived from gastrointestinal tract cancer is rare, and overall patient survival is poor. CONCLUSION: RPA class, chemotherapy after brain metastases, and treatment regimens were independent prognostic factors for the survival of patients with brain metastases derived from gastrointestinal cancers.

Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors.

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor (VEGF)], proliferative index (Ki67), and prognosis of patients with gastrointestinal stromal tumors (GIST). METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin (CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density (IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF, Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5% positive cells. The prognosis was classified as good (patient alive without recurrence) or poor (patient with recurrence/death). RESULTS: The distribution of tumor sites among the 54 analyzed samples was as follows: 27 (50%) in the stomach, 20 (37.1%) in the small intestine, 6 (11.1%) in the colon, and 1 (1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm (median: 8 cm); in 12 cases (22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases (77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis (P < 0.001). The cut-off values of CD105 (> 1.2%) and CD31 (> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis. Cases with a better prognosis showed significantly null/weak staining for VEGF (P < 0.001). Ki-67 expression of ≥ 5% was strongly correlated with a worse prognosis (P < 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis. CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.

Management of liver metastases of gastrointestinal stromal tumors (GIST).

INTRODUCTION: Liver metastases (LM) are crucial prognostic manifestation of gastrointestinal stromal tumors (GIST). With the advent of tyrosine kinase inhibitors (TKI), management of metastatic GIST has radically changed. Long clinical follow-up provides an increased proportion of GIST patients with LM who are candidates for potentially curative therapy. MATERIAL AND METHODS: Patients who underwent treatment for liver metastases of GIST between 2000-2009 in our department were included in the study. Mean follow-up was 84 months (range 40-145) months. In retrospective analysis we investigated clinical, macro-/microscopic and immunohistochemical criteria, surgical, interventional and TKI therapy as well. RESULTS: In 87 GIST-patients we identified 25 (29%) patients with metastatic disease. Of these, 12 patients (14%) suffered from LM with a mean age of 60.5 (range, 35-75) years. Primary GIST were located at stomach (n = 4, 33%) or small intestine (n = 8, 67%); all of them expressed CD117 and/or CD34. LM were multiple (83%), distributed in both lobes (67%). They were detected synchronously with primary tumor in 33% and metachronously in 77%. All patients with liver involvement were considered to treatment with TKI. LM were resected (R0) in 4 patients (33%). In recurrent (2/4) and TKI resistant cases, interventional treatment (radiofrequency ablation) and TKI escalation were carried out. During a median follow-up of 84 months (range 30-152), 2 patients died (16.5%) for progressive disease and one patient for other reasons. Nine patients (75%) were alive. CONCLUSION: Treatment of LM from GIST needs a multimodal approach. TKI-therapy is required at any case. In case of respectability, surgery must be carried out. In unresectable cases or recurrent/progressive disease, interventional treatment or TKI escalation should be considered. Therefore, these patients need to be treated in experienced centres, where multimodal approaches are established.

Assessment of early response to imatinib 800 mg after 400 mg progression by ¹8F-fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal tumors.

INTRODUCTION: Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients. PATIENTS & METHODS: After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS). RESULTS: EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05). CONCLUSION: The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

Relación entre estado nutricional y evolución postoperatoria, en cirugía oncológica digestiva / Nutritional status and postoperative complications in patients with digestive cancer

Background: Risk of malnutrition is elevated among oncologic patients, and this increases postoperative morbidity and mortality. Aim: To study the association between nutritional status and postoperative outcomes in a group of patients with gastrointestinal cancers. Patients and Methods: We studied 129 patients with diagnosis of digestive cancer, previous to potentially curative surgery. Nutritional status was evaluated through anthropometric measures, Subjective Global Assessment (SGA), dietary intake recalls and routine biochemical parameters. Functional performance was assessed by the Karnofsky index (KI). Cancer stage was classified according to TNM4. During the postoperative period, complications, length of stay at the critical care ward and duration of hospitalization were registered. Thirty days after discharge, patients were contacted, and the appearance of new complications was listed. Results: According to SGA 14.7% of patients were classified as well nourished (A), 57.3% as moderately undernourished or at risk of malnutrition (B) and 27.9% as severely malnourished (C). The incidence of total complications was 25.5%. Nutritional status was not associated with cancer stage. The frequency of complications among patients classified as A, B and C were 5.5, 25.3 and 37.1% respectively (p = 0.03). Conclusions: We detected a high frequency of malnutrition in this group of patients. Overall the frequency of postoperative complications was low, however malnourished patients exhibited a higher rate of surgical complications.

[Nutritional status and postoperative complications in patients with digestive cancer]. / Relación entre estado nutricional y evolución postoperatoria, en cirugía oncológica digestiva.

BACKGROUND: Risk of malnutrition is elevated among oncologic patients, and this increases postoperative morbidity and mortality. AIM: To study the association between nutritional status and postoperative outcomes in a group of patients with gastrointestinal cancers. PATIENTS AND METHODS: We studied 129 patients with diagnosis of digestive cancer, previous to potentially curative surgery. Nutritional status was evaluated through anthropometric measures, Subjective Global Assessment (SGA), dietary intake recalls and routine biochemical parameters. Functional performance was assessed by the Karnofsky index (KI). Cancer stage was classified according to TNM4. During the postoperative period, complications, length of stay at the critical care ward and duration of hospitalization were registered. Thirty days after discharge, patients were contacted, and the appearance of new complications was listed. RESULTS: According to SGA 14.7% of patients were classified as well nourished (A), 57.3% as moderately undernourished or at risk of malnutrition (B) and 27.9% as severely malnourished (C). The incidence of total complications was 25.5%. Nutritional status was not associated with cancer stage. The frequency of complications among patients classified as A, B and C were 5.5, 25.3 and 37.1% respectively (p = 0.03). CONCLUSIONS: We detected a high frequency of malnutrition in this group of patients. Overall the frequency of postoperative complications was low, however malnourished patients exhibited a higher rate of surgical complications.

Prevalence and management of anaemia in patients with non-myeloid cancer undergoing systemic therapy: a Spanish survey.

BACKGROUND: The present study aimed to provide updated data on anaemia prevalence and management in cancer patients undergoing systemic therapy in Spain. METHODS: This was a multicenter, observational, cross-sectional study performed in 2008. Eligible patients were ≥18 years, with non-myeloid malignancies treated with systemic therapy [chemotherapy (CT), hormonal therapy or immunotherapy]. Anaemia was defined according to WHO as haemoglobin (Hb) < 12 g/dL. RESULTS: The study included 214 patients with a median age of 63 years (range 20-91), 58 % women, 73 % with solid tumours, and 79 % with advanced disease. CT was used in 91 % of patients (26 % with platinum compounds), hormonal therapy in 8.5 %, and immunotherapy in 8.5 %. In our study, 48.1 % of patients [95 % confidence interval (CI) 45.2-58.6] showed anaemia (31 % symptomatic): 42.0 % mild (10 ≤ Hb ≤ 11.9 g/dL), 5.6 % moderate (8 ≤ Hb ≤ 9.9 g/dL), and 0.5 % severe (Hb < 8 g/dL). A higher prevalence was observed in patients treated with CT (51 vs. 20 %, p = 0.01), platinum-based CT (70 vs. 47 %, p = 0.01) or palliative CT (61 vs. 39 %, p = 0.003). Anaemia was also more frequent in patients with more than three lines of CT (83 %) and in the fourth or subsequent CT cycle (58 %). Management in the previous 4 weeks in patients with anaemia was: 62 % did not receive treatment (92 % mild), 24 % received erythropoiesis-stimulating agents (ESAs), 14 % received iron and 8.7 % received transfusion. CONCLUSIONS: In Spanish hospitals, about half of patients with non-myeloid malignancies undergoing systemic therapy fulfilled anaemia criteria (87 % mild). Approximately two-third of patients with anaemia do not receive specific treatment and ESA use is below current guidelines.

[Surgical prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP NET)]. / Tumor neuroendocrino gastroenteropancreático. Factores pronósticos quirúrgicos.

OBJECTIVE: to determine surgical prognostic variables from a retrospective cohort of histopathologically confirmed gastroenteropancreatic neuroendocrine tumors (GEP-NET) in Mexican subjects. METHODS: consecutive patients treated for GEP-NET from 1999 through 2007 at Oncological Hospital were included. Demographic, clinical variables, disease-free survival were retrieved. RESULTS: forty-eight patients were included, 29 (60.4 %) female with a mean age of 54 years. Overall survival time was 43.7 months and disease-free survival was 33 months. Negative statistically significant overall survival time predictors were 2 and 3 histological types (HR 5.5. CI 2.0-21, p = 0.0001), tumor size > 2 cm (HR 8.8, CI 1 .29-75, p = 0.002), the presence of metastasis (HR 2.4, CI 1.2-9.6, p = 0.0001) and tumor resectability (HR 9.8, CI 2.9-40.2, p = 0.0001). For the disease-free period, only the histological type (2 or 3) was a negative outcome variable. CONCLUSIONS: histological type, tumor size, the presence of metastasis, and tumor non resectability were significant survival predictors.

Tumores estromales gastrointestinales: evaluación clinicopatológica y sobrevida en el Hospital Rebagliati / Gastrointestinal stromal tumors: clinicopathologic and survival evaluation in Rebagliati Hospital

OBJETIVO: Determinar las manifestaciones clínicas, radiológicas, histopatológicas y sobrevida de los pacientes con Tumor Estromal Gastrointestinal (GIST) en el Hospital Nacional Edgardo Rebagliati Martins (HNERM), de Lima, Perú. MATERIAL Y MÉTODOS: El presente es un estudio descriptivo, retrospectivo. El cual se realizó a partir de las historias clínicas de 103 pacientes con GIST confirmado por inmunohistoquímica que fueron evaluados y tratados en el HNERM, desde Enero del 2002 hasta Diciembre de 2010. RESULTADOS: En los 103 pacientes el promedio de edad fue 64 años (entre 30 y 88 años). Predominó en mujeres (52%). El tiempo de enfermedad promedio fue 7 meses. La forma de presentación más frecuente fue sangrado digestivo (48.3%). El diagnóstico se hizo más por endoscopía (50.5%). La prevalencia por órganos fue más frecuente en estómago 56.3%. El promedio de tamaño fue 98mm, (49% entre 50mm y 100mm), el tumor de mayor tamaño alcanzaba 260 mm. El estadio tumoral más frecuente fue localizado (70.9%). Presentaron otro cáncer asociado el 9.7% de pacientes El patrón histológico predominante fue fusiforme 73.8%. El 84.5% tuvo bajo índice mitótico. La inmunohistoquímica mostró la expresión de KIT (CD 117) 94.17%, CD 34 77.5%, Vimentina 96.6%, NSE 84.9%, Alfa actina 52.7%, CD56 44.4%, S-100 32.3% y Actina 20.0%. La característica tomográfica más frecuente fue tumor heterogéneo (43.6%). La distribución según clasificación de riesgo fue: muy bajo riesgo 3.9%, bajo riesgo 28.2%, riesgo intermedio 37.7% y alto riesgo 30.1%. La resección quirúrgica completa se realizó en 87.4% de pacientes, 4.9% de pacientes recibió Imatinib. La sobrevida global acumulada a 5 años fue 31.07%. En el análisis bivariado se encontró asociación estadística entre el haber sobrevivido con: ausencia de cáncer asociado p= 0.004, CD 34 p=0.01, índice mitótico bajo p=0.00 y tratamiento quirúrgico recibido p= 0.000. En el análisis multivariado se encontró asociación estadística de mayor sobrevida con: los de menor tamaño del tumor p=0.015 (IC -3.67, -0.41), estadio tumoral localizado p=0.036 (IC -5.83, -0.19), menor índice mitótico p=0.038 (IC -0.86, 0.02), paciente asintomático p=0.009 (IC 1.25, 8.62), no recidiva del tumor p=0.01 (IC -8.49, -1.17) y el no presentar metástasis p=0.001 (IC 2.66, 10.62). CONCLUSIONES: Los resultados de nuestro estudio fueron similares a lo que reporta la literatura internacional. Los factores que se asociaron a mayor sobrevida fueron: haber recibido tratamiento quirúrgico, pacientes con menor tamaño tumoral, estadio tumoral localizado, índice mitótico bajo, paciente asintomático, no recidiva del tumor, no metástasis y no cáncer asociado.

OBJECTIVE: To determine the clinical, radiological, histopathological manifestations and survival of patients with gastrointestinal stromal tumor (GIST)in the National Hospital Edgardo Rebagliati Martins (HNERM) from Lima, Perú. MATERIAL AND METHODS: This is a descriptive and retrospective study, which was based on the medical records of 103 patients with confirmed GIST with immunohistochemical. All the patients were evaluated and treated at the HNERM, from January 2002 until December 2010. RESULTS: In 103 patients between 30 and 88 years the average age was 64 years. The tumor was more frequent in females (52%). The mean disease duration was 7 months. The most frequent form of presentation was gastrointestinal bleeding (48.3%). The diagnosis was made more by endoscopy (50.5%). The prevalence of GISTs by organs was more frequent in stomach (56.3%). The average size of the tumors was 98mm, 49% had a size between 50mm and 100mm, the largest tumor was 260 mm. Tumor stage more frequent was localized (70:9%). GIST associated with another cancer was 9.7% of patients. The predominant histologic pattern was fusiform (73.8%). The 84.5% had low mitotic index. Immunohistochemistry showed expression KIT (CD 117) was 94.17%, CD34 77.5%, Vimentin 96.6%, NSE 84.9%, alpha actin 52.7%, CD56 44.4%, S-100 32.3% and Actin 20%. The tomographic characteristic more frequent was heterogeneous tumor (43.6%).The distribution according to risk classification was: very low risk 3.9%, low risk 28.2, intermediate risk 37.7% and high risk 30.1%. Complete surgical resection was performed in 87.4% of patients and 4.9% of patients received imatinib. The cumulative overall survival at 5 years was 31.07%. In bivariate analysis statistical association was found between surviving with: no presence of cancer associated p = 0.004, CD 34 p = 0.01, low mitotic index p = 0.00 and received surgical treatment p = 0.000. In multivariate analysis one found statistical association of longer survival with smaller tumor size p = 0.015 (CI -3.67, -0.41), localized tumor stage p = 0.036 (CI -5.83, -0.19), lower mitotic index p = 0.038 (CI -0.86, 0.02), asymptomatic patient p=0.009 (CI 1.25, 8.62), no tumor recurrence p = 0.01 (CI -8.49, -1.17), and no metastasis p = 0.001 (CI 2.66, 10.62). CONCLUSIONS: The results of our study were similar to what was reported in international literature. Factors that were associated with longer survival were receiving surgical treatment, patients with smaller tumor size, tumor stage localized, low mitotic index, asymptomatic patient, not tumor recurrence, not metastasis and no cancer associated.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: initial experience in Oaxaca, Mexico.

Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multimodality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.

Ki-67 expression score correlates to survival rate in gastrointestinal stromal tumors (GIST).

PURPOSE: To evaluate the immunohistochemical expression of p16, Ki-67, p53 and Bcl-2 proteins in gastrointestinal stromal tumors (GIST); to assess the possible association between these variables and clinical and histopathological factors of cancer; and to check for prognostic value of these variables (survival and recurrence). METHODS: A sample of 55 patients treated surgically for GIST in three hospitals was studied. The surgically excised tumors were confirmed as GIST by KIT, vimentin, desmin S100 protein, CD117, 1A4 and CD34 assessment in paraffin blocks. RESULTS: Only 9 (16%) cases of GIST were positive for p53, p16 was positive among 43.6%; 80% of GISTs showed staining for Bcl-2. The proliferative index (expressed as the proportion of positive cells) assessed by immunohistochemical expression of Ki-67 was high in 49% of cases. Elevated Ki-67 scores were associated to high histological grade (p=0.0026) and mitosis index, MI (p=0.0001). High Ki-67 index was associated to death. Expression of p53, p16 and Bcl-2 did not correlate to morphological or clinical variables. CONCLUSIONS: Ki-67 immunohistochemical evaluation should be included in preoperative evaluation of GIST biopsies or surgical specimens as a prognostic tool for clinical staging; and all other proteins studied (Bcl-2, p53 and p16) did not play a role in GIST metabolic or carcinogenic process, remaining without prognostic value.