Is advanced esophageal adenocarcinoma a distinct entity from intestinal subtype gastric cancer? Data from the AGAMENON-SEOM Registry.

BACKGROUND: Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical trials rarely include EAC. This work sought to compare clinical characteristics and treatment outcomes of advanced EAC with those of GEJ-AC and GAC and examine prognostic factors. PATIENTS AND METHODS: Participants comprised patients with advanced EAC, intestinal GEJ-AC, and GAC treated with platin and fluoropyrimidine (plus trastuzumab when HER2 status was positive). Overall and progression-free survival were estimated using the Kaplan-Meier method. Cox proportional hazards regression gauged the prognostic value of the AGAMENON model. RESULTS: Between 2008 and 2019, 971 participants from the AGAMENON-SEOM registry were recruited at 35 centers. The sample included 67.3% GAC, 13.3% GEJ-AC, and 19.4% EAC. Pulmonary metastases were most common in EAC and peritoneal metastases in GAC. Median PFS and OS were 7.7 (95% CI 7.3-8.0) and 13.9 months (12.9-14.7). There was no difference in PFS or OS between HER2- and HER2+ tumors from the three locations (p > 0.05). Five covariates were found to be prognostic for the entire sample: ECOG-PS, histological grade, number of metastatic sites, NLR, and HER2+ tumors treated with trastuzumab. In EAC, the same variables were prognostic except for grade. The favorable prognosis for HER2+ cancers treated with trastuzumab was homogenous for all three subgroups (p = 0.351) and, after adjusting for the remaining covariates, no evidence supported primary tumor localization as a prognostic factor (p = 0.331). CONCLUSION: Our study supports the hypothesis that EAC exhibits clinicopathological characteristics, prognostic factors, and treatment outcomes comparable to intestinal GEJ-AC and GAC.

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.

Intervention in gastrointestinal stromal tumour with a high risk of malignancy and associated with thalassaemia minor.

This study reports on a 65-year-old female patient with controlled comorbidity, who was diagnosed with gastrointestinal stromal tumours following regular monitoring of renal cysts. After the surgical treatment, coadjuvant treatment with imatinib was initiated. After a few months, the patient complained of angor and asthenia and the diagnosis of anaemic syndrome was made on the basis of blood test results. We studied the causes of the anaemia (maturation factors and other causes of secondary anaemia) and it led to the diagnosis of vitamin B12 deficiency. Treatment with vitamin B12 supplementation was initiated. With the correction of the vitamin levels with supplementation, the symptoms improved. Thalassaemia led to the misdiagnosis of vitamin B12 deficiency because of the lower mean corpuscular volume levels.

Open-label trial on efficacy and security of treatment with gemcitabine and oral modulation with tegafur and levofolinic acid (GEMTG) in patients with advanced pancreatic cancer.

AIM: Advanced pancreatic cancer has a bad prognosis, with a median overall survival (OS) no longer than 4-6 months. Since the end of last century, monotherapy with gemcitabine has remained the elective therapy, but new schedules are needed in order to improve these results. We aim to evaluate the efficacy of tegafur and levofolinic acid (LV) associated with gemcitabine, as well as its toxicity, progression-free survival and OS in advanced pancreatic cancer. PATIENTS AND METHODS: An open-label, multicentric, prospective, non-controlled trial was carried out on patients with advanced or disseminated pancreatic cancer. Gemcitabine 1250 mg/m² was administered on the 1st and 8th days of the cycle, tegafur 750 mg/m²/day for 21 consecutive days and LV 25 mg/day continuously, every 28 days, with a maximum of six cycles. The primary variable was tumour overall response rate (ORR). Secondarily, time to progression (TTP), OS and scheme toxicity were determined. RESULTS: Forty patients were recruited; the male/female ratio was 30:10, with a mean age of 61 years. Forty percent had a Karnofsky index of 90% or 100%. Only 11 patients (27%) completed the six cycles of treatment, but more than 50% received three or more cycles. Dose intensity was 89.56% for gemcitabine and 87.36% for tegafur. Efficacy ORR was 22.5% (CI 95%, 6-37%). TTP was 3.87 months (CI 95%, 2.1-5.6), time to treatment failure was 2.97 months (CI 95%, 2.43-4.67) and OS 6.3 months (CI 95%, 4-7). The chemotherapeutic combination was well accepted; most haematologic and non-haematologic toxicities were grade 1 or 2. The most prevalent grade 3/4 toxicities were asthenia (30%), liver biochemistry disorders (25%), diarrhoea (15%) and stomatitis (12%). CONCLUSIONS: The administration of gemcitabine, associated with oral tegafur and leucovorin, has activity against advanced pancreatic cancer, with an adequate toxicity profile.

Haemolytic uraemic syndrome associated with gemcitabine.

Haemolytic uraemic syndrome (HUS) is a rare thromboembolic complication observed in patients with cancer. It is characterised by the clinical triad of acute renal failure, microangiopathic haemolytic anaemia and thrombocytopaenia. It may be associated with a variety of aetiologies, including chemotherapeutic agents such as mitomycin, cisplatin, bleomycin, 5-fluorouracil and, most recently, gemcitabine. We report a 70-year-old patient treated with gemcitabine who developed haemolytic uraemic syndrome.

[Site of local surgery in adenocarcinoma of the rectum T2N0M0]. / Lugar de la cirugía local en el adenocarcinoma de recto T(2)N(0)M(0).

INTRODUCTION: The local exeresis adenocarcinoma of the rectum T(2)N(0)M(0) (ADC-T2), using transanal endoscopic microsurgery (TEM), has the benefit of achieving lower morbidity with a better quality of life. However, local occurrence of the local exeresis is greater than 20%, which is unacceptable these days. PATIENTS AND METHODS: Prospective, observational follow up study. The tumours committee agreed that those ADC-T2 patients could have the following treatments: total mesorectal excision (TME), simple TEM, TEM with postoperative chemo- and radiotherapy (Ct-Rt), preoperative Ct-Rt with subsequent TEM and radical surgical rescue (TME) within at least 4 weeks. RESULTS: Of the 146 patients operated on using TEM, 75 had adenocarcinomas, 59 adenomas, 6 scarring wounds, 5 carcinoids and 1 GIST. Of the adenocarcinomas 22 were ADC-T2. Follow up: median of 16 months (range, 3-32 months). The overall local recurrence was 18% (4/22). According to the treatment strategy the local occurrence was: TEM as the only procedure, 20% (2/10). Radical surgical rescue was performed on 3 patients after TEM, with no local or systemic recurrences. TEM with Qt-Rt after surgery was performed on 6 patients, with a local recurrence of 33% (2/6). Ct-Rt and subsequent TEM in 3 patients, with no local or systemic recurrences. CONCLUSIONS: Treatment of ADC-T2 using simple TEM is not effective. The combination of Ct-Rt after TEM, does not improve the results of TME. It is possible to rescue those patients without changing the overall survival. Preoperative Ct-Rt and TEM appears to be the approach that obtains a clinical and histological response, although a response is needed by clinical trials.

Lugar de la cirugía local en el adenocarcinoma de recto T2N0M0 / Site of local surgery in adenocarcinoma of the rectum T2N0M0

Introducción: la exéresis local del adenocarcinoma de recto T2N0M0 (ADC-T2), mediante microcirugía endoscópica transanal (TEM), se beneficia en conseguir una menor morbilidad con mejor calidad de vida. Sin embargo, la recidiva local de la exéresis local es superior al 20%, inaceptable en estos momentos. Pacientes y método: estudio observacional de seguimiento prospectivo. Los pacientes ADC-T2 son consensuados en el comité de tumores a las actuaciones terapéuticas: escisión total del mesorrecto (ETM), TEM simple, TEM con quimiorradioterapia (Qt-Rt) postoperatoria, Qt-Rt preoperatoria con posterior TEM y rescate a cirugía radical (ETM) en menos de 4 semanas. Resultados: se ha intervenido a 146 pacientes mediante TEM; 75 adenocarcinomas, 59 adenomas, 6 lesiones cicatriciales, 5 carcinoides y 1 GIST. De los adenocarcinomas, 22 fueron ADC-T2. Seguimiento: mediana, 16 (intervalo, 3-32) meses. La recidiva local total ha sido del 18% (4/22). Según la estrategia terapéutica la recidiva local fue: TEM como único procedimiento en el 20% (2/10). Se realizó en 3 pacientes rescate a cirugía radical tras TEM, sin recidiva local ni sistémica. TEM con Qt-Rt posterior a la cirugía se realizó en 6, con una recidiva local del 33% (2/6). Se practicó Qt-Rt y posteriormente TEM en 3 pacientes, sin recidiva local ni sistémica. Conclusiones: el tratamiento del ADC-T2 mediante TEM simple no es razonable. La asociación de Qt-Rt tras TEM, no consigue mejorar los resultados a la ETM. Es factible rescatar a los pacientes sin que altere la supervivencia total. La Qt-Rt preoperatoria y TEM parece ser la línea cuando se consiga una respuesta histológica y clínica, aunque es necesaria la respuesta por parte de ensayos clínicos (AU)

Introduction: The local exeresis adenocarcinoma of the rectum T2N0M0 (ADC-T2), using transanal endoscopic microsurgery (TEM), has the benefit of achieving lower morbidity with a better quality of life. However, local occurrence of the local exeresis is greater than 20%, which is unacceptable these days. Patients and methods: Prospective, observational follow up study. The tumours committee agreed that those ADC-T2 patients could have the following treatments: total mesorectal excision (TME), simple TEM, TEM with postoperative chemo- and radiotherapy (Ct-Rt), preoperative Ct-Rt with subsequent TEM and radical surgical rescue (TME) within at least 4 weeks. Results: Of the 146 patients operated on using TEM, 75 had adenocarcinomas, 59 adenomas, 6 scarring wounds, 5 carcinoids and 1 GIST. Of the adenocarcinomas 22 were ADC-T2. Follow up: median of 16 months (range, 3¿32 months). The overall local recurrence was 18% (4/22). According to the treatment strategy the local occurrence was: TEM as the only procedure, 20% (2/10). Radical surgical rescue was performed on 3 patients after TEM, with no local or systemic recurrences. TEM with Qt-Rt after surgery was performed on 6 patients, with a local recurrence of 33% (2/6). Ct-Rt and subsequent TEM in 3 patients, with no local or systemic recurrences. Conclusions: Treatment of ADC-T2 using simple TEM is not effective. The combination of Ct-Rt after TEM, does not improve the results of TME. It is possible to rescue those patients without changing the overall survival. Preoperative Ct-Rt and TEM appears to be the approach that obtains a clinical and histological response, although a response is needed by clinical trials (AU)

Long-term follow-up of local rectal cancer surgery by transanal endoscopic microsurgery.

BACKGROUND: In 1997 we launched a prospective program of transanal endoscopic microsurgery (TEM) for the treatment of rectal cancer. METHODS: Suitability for TEM was based on endorectal ultrasound results, classified as follows: (I) benign tumors; (II) adenocarcinomas uT0 and uT1 with uN0; (III) adenocarcinomas uT2- uN0, low histological grade with intention to cure; and (IV) advanced stage adenocarcinomas with palliative care RESULTS: Transanal endoscopic microsurgery was performed in 218 patients: 122 adenomas, and 96 adenocarcinomas: group II-72, group III-19, and group IV-5. Follow-up was >24 months (median 59 months) in 61 patients. Nine were lost to follow-up, and so 52 patients were studied: group II-38, group III-11, and group IV-3. The Kaplan-Meier probability of nonrecurrence of adenocarcinoma by group was 93% in tumors in situ (Tis) and T1; and 77.8% in T2. The Kaplan-Meier probability of survival by group was 100% in Tis and T1 and 82% in T2. CONCLUSIONS: Rates of recurrence and long-term survival in Tis and T1 adenocarcinomas treated with TEM are similar to those in previously published reports using conventional surgery. Further studies are required in T2 adenocarcinomas to determine a definitive strategy.

Gastrointestinal stromal tumors: experience in 49 patients.

INTRODUCTION: Gastrointestinal stromal tumours (GIST) are mesenchymal tumours of the digestive tract originated in the interstitial cells of Cajal. They express the tyrosine kinase c-kit (CD117) activity receptor. Mutations in this receptor cause neoplastic development. Curative treatment continues to be radical resection of the tumour and is resistant to commonly employed chemotherapy regimens. Imatinib mesilate is a drug that inhibits c-kit activity expressed by GIST and its activity in these tumours has been demonstrated. MATERIAL AND METHODS: Retrospective study of all cases of leiomyoma, leiomyosarcoma, schwannoma, and stromal or mesenchymal tumors from 1989 to July 2004. C-kit and CD34 proteins were detected at immunohistochemical study in addition to the usual markers for mesenchymal tumours. RESULTS: 49 GISTs were diagnosed, 26 males and 23 females (mean age 64.1). Symptoms were digestive tract bleeding (n = 13), abdominal pain (n = 13), intestinal occlusion (n = 4) and others. The lesion was located in small bowel (n = 22), stomach (n = 19), rectum (n = 3), peritoneum (n = 2), esophagus (n = 1), omentum (n = 1), and retroperitoneum (n = 1). Forty-three of the 49 patients underwent surgery; radical resection was performed in 37 (75.5%) and palliative surgery in the other six (16.2%). Two of the patients that did not undergo surgery received chemotherapy. At the time of study, 28 (57.14%) patients remained alive, 23 (46.9%) of whom were disease- free and five (10.2%) were not. Nineteen (38.7%) patients died. CONCLUSIONS: The results of our series are similar to the others published. Before the year 2001, surgery was the only successful option for the GIST. Surgical resection continues being the best treatment to definitively cure this disease. Imatinib is used to treat not only resectable tumours, but even to allow the possibility to make a subsequent rescue surgery. On the other hand, Imatinib is used in the treatment of the metastatic disease.

Gastrointestinal stromal tumors: experience in 49 patients

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Introduction. Gastrointestinal stromal tumours(GIST) are mesenchymal tumours of the digestivetract originated in the interstitial cells of Cajal. Theyexpress the tyrosine kinase c-kit (CD117) activityreceptor. Mutations in this receptor cause neoplasticdevelopment. Curative treatment continues to beradical resection of the tumour and is resistant tocommonly employed chemotherapy regimens. Imatinibmesilate is a drug that inhibits c-kit activityexpressed by GIST and its activity in these tumourshas been demonstrated.Material and methods. Retrospective study of allcases of leiomyoma, leiomyosarcoma, schwannoma,and stromal or mesenchymal tumors from 1989to July 2004. C-kit and CD34 proteins were detectedat immunohistochemical study in addition to theusual markers for mesenchymal tumours.Results. 49 GISTs were diagnosed, 26 males and 23females (mean age 64.1). Symptoms were digestivetractbleeding (n = 13), abdominal pain (n = 13), intestinalocclusion (n = 4) and others. The lesion waslocated in small bowel (n = 22), stomach (n = 19),rectum (n = 3), peritoneum (n = 2), esophagus (n = 1),omentum (n = 1), and retroperitoneum (n = 1).Forty-three of the 49 patients underwent surgery;radical resection was performed in 37 (75.5%) andpalliative surgery in the other six (16.2%). Two ofthe patients that did not undergo surgery receivedchemotherapy. At the time of study, 28 (57.14%) patientsremained alive, 23 (46.9%) of whom were disease-free and five (10.2%) were not. Nineteen (38.7%)patients died.Conclusions. The results of our series are similar tothe others published. Before the year 2001, surgerywas the only successful option for the GIST. Surgicalresection continues being the best treatmentto definitively cure this disease. Imatinib is used totreat not only resectable tumours, but even to allowthe possibility to make a subsequent rescue surgery.On the other hand, Imatinib is used in the treatmentof the metastatic disease