RESUMEN
PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Gástricas , Humanos , Masculino , Anciano , Femenino , Neoplasias Gástricas/terapia , Reparación de la Incompatibilidad de ADN , Homólogo 1 de la Proteína MutL , Neoplasias Colorrectales/patología , Estudios Observacionales como AsuntoRESUMEN
The results reported in the literature in the context of an R1 situation for a resected gastric carcinoma are not uniform. An R1 situation worsens the prognosis for the long-term survival of patients. This is significant especially for low T stages and lymph node metastasis with 0-≤3 lymph node metastases. In higher tumor stages with extensive lymph node metastases, the survival difference between R0 and R1 resections is lower and frequently no longer significant. The frequency of R1 resection is approximately 5% (range 1.8-9%) and for adenocarcinoma of the esophagogastric junction (AEG tumors)> 10%. The data are mainly related to the oral and aboral resection line but there are only a few specifications on the circumferential margin. The risk of an infiltrated resection line increases with the size of the tumor (>5 cm), T3+4 and pN2/pN3 stages. Poorly differentiated signet ring cell or mucinous adenocarcinomas and carcinomas of the Bormann type 3+4 also lead to an increased R1 rate. In order to achieve an R0 resection, an intraoperative frozen section is the standard approach. Immediate reoperation should be performed in the case of tumor infiltration. If an R1 resection is detected only in the definitive histology, surgical re-excision to achieve an R0 resection is the standard approach in publications. Nevertheless, a reoperation is rare. Only 1 study showed 122 patients with 100% re-operations, which were successfully performed in 50 patients (41% R0). For the R0 group, median survival was extended from 18 months to 23 months. There are only sporadic literature data and no evidence for postoperative additive treatment (chemotherapy, radiotherapy and radiochemotherapy).
Asunto(s)
Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Terapia Combinada , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Femenino , Secciones por Congelación , Adhesión a Directriz , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Márgenes de Escisión , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Reoperación , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: The oncological outcome of patients with rectal cancer has improved considerably over the past few decades. This is mainly due to the introduction of the surgical concept of total mesorectal excision (TME) and the implementation of multimodal treatment strategies. Additionally, it has recently been demonstrated that the oncological results of open and laparoscopic TME are comparable. For some time there has been an ongoing debate on the potential relevance of robotic assistance systems in visceral surgery. The aim of this study was to evaluate the operative and perioperative outcomes of patients with rectal or rectosigmoid cancer, who were operated on using the Da Vinci Surgical System. PATIENTS AND RESULTS: We retrospectively analysed the outcomes of 202 consecutive patients, who were operated between September 2010 and November 2015 in three Surgical Centers. The cohort consisted of 136 men and 66 women with a mean BMI of 28. We performed the following procedures: 49 anterior rectal resections, 119 low anterior rectal resections, and 34 abdominoperineal excisions. Conversion to an open procedure was required in 13 patients. Non-surgical complications (n = 27) occurred in 24 patients (12%) and surgical complications (n = 67) in 62 patients (31%). Most complications were due to abdominal or sacral wound infections (n = 25) and anastomotic leaks (n = 18). The mortality rate within 30 days was 2%. The rate of R0 resections was 95%, with circumferential resection margins being negative in 98% of the patients. The quality of the mesorectal resection was scored as good in 91% of the patients. CONCLUSIONS: The Da Vinci Surgical System can be used safely and with a low complication rate for surgical treatment of rectal cancer. While primary evidence suggests that the outcome of robotic-assisted surgery is comparable with open and laparoscopic surgery, its definitive value has to be determined upon publication of the prospective randomized ROLARR trial. The main advantages of the Da Vinci system are its endowristed instruments with multiple degrees of freedom and its optimised visualisation (3D, stable camera platform controlled by the surgeon). Another positive feature is the significant ergonomic advantage for the surgeon.
Asunto(s)
Laparoscopía/instrumentación , Laparoscopía/métodos , Proctoscopía/instrumentación , Proctoscopía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colon Sigmoide/patología , Colon Sigmoide/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Neoplasias del Recto/patología , Recto/patología , Recto/cirugía , Estudios Retrospectivos , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/cirugía , Equipo Quirúrgico , Instrumentos Quirúrgicos , Adulto JovenRESUMEN
BACKGROUND AND AIM: In Germany, data of cancer patients are recorded not only in epidemiological registers but also in clinical cancer registers. To ensure the networking of all included medical partners, quality control, and clinical research it is necessary that cancer cases are captured more or less completely. The aim of the present study was to compare the data sets of two registers. PATIENTS AND METHODS: Data from patients with colorectal cancer from two large surgical clinics in Magdeburg are recorded in two registers - the Clinical Cancer Registry Magdeburg and the Institute of Quality Assurance in Operative Medicine at the Otto-von-Guericke University Magdeburg. Here we compared the data sets in order to check the completeness of data capturing and to determine factors influencing the degree of completeness. RESULTS: From all patients captured in the Institute of Quality Assurance, 78.9% are found also in the clinical cancer registry. The percentage improves over the course of time, but also depends on diagnostic criteria such as the staging. There are some differences between both registries, explainable by their specific objectives. Particularly, it is demonstrated that incomplete follow-up record may bias estimates of survival rates from registries. CONCLUSION: Ensuring the completeness and correctness of data is a major challenge for cancer registries. It has distinct influence on estimated quality parameters such as survival rates.
Asunto(s)
Neoplasias Colorrectales/epidemiología , Sistema de Registros/normas , Adulto , Anciano , Anciano de 80 o más Años , Sesgo , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiología , Carcinoma in Situ/terapia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Femenino , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/terapia , Alemania/epidemiología , Humanos , Linfoma/diagnóstico , Linfoma/epidemiología , Linfoma/terapia , Masculino , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/terapia , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/terapia , Percepción de Cercanía , Proyectos de Investigación/normas , Sarcoma/diagnóstico , Sarcoma/epidemiología , Sarcoma/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/terapia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Adenocarcinomas of the oesophagogastric junction are increasingly being considered as a separated tumour entity. The prognosis is rather poorer compared with that for distal gastric cancer. Data from a multicentre study as part of research on clinical care aim to reflect the current situation in surgical treatment after inauguration of neoadjuvant modalities. PATIENTS AND METHOD: As part of the ongoing prospective multicentre observational study QCGC 2 (German Gastric Cancer Study 2), 544 adenocarcinomas of the oesophagogastric junction (AEG 1-3) were registered from 01/01/2007 to 12/31/2009. RESULTS: Patients underwent surgical intervention in 108 (76.6 %) of the 141 surgical departments which provided data to the study. In 391 patients (82.5 %), R0 resection was achieved. Almost 60 % of the carcinomas of the oesophagogastric junction were approached in departments with no more than 10 of these tumour lesions through the whole study period (3 years). Endoscopic ultrasonography was performed in 283 cases (53 %); the rate of neoadjuvant treatment was 34.4 % (n = 187). Intraoperative fresh frozen section was only included in intraoperative decision-making in 242 patients (60.8 %). In the revealed heterogeneous spectrum of surgical interventions, a limited number of transthoracic approaches (20 %) and a mediastinal lymphadenectomy rate of only 47 % were found. Hospital lethality was 6.6 %. In the adenocarcinomas of the oesophagogastric junction, a significantly lower median survival (25 months) compared with distal gastric cancer (38 months) was observed depending on the tumour stage. In addition, 5-year survival rate of AEG patients (33.1 %) was distinctly lower than for patients with distal gastric cancer (41.4 %). There was no significantly better survival by neoadjuvant treatment in the group of investigated patients. CONCLUSION: The results in the treatment of carcinomas of the oesophagogastric junction in the multicentre setting including surgical departments of each profile and region even after introduction of multimodal therapeutic concepts are not satisfying. In particular, modern diagnostic and surgical strategies need to be widely used or their percentage has to be increased. In this context, centralisation of the surgical care of this specific tumour entity appears reasonable.
Asunto(s)
Adenocarcinoma/cirugía , Unión Esofagogástrica/cirugía , Neoplasias Gástricas/cirugía , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Unión Esofagogástrica/patología , Femenino , Secciones por Congelación , Mortalidad Hospitalaria , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Adulto JovenRESUMEN
The aim of the review is to compare the results of selected German multicenter observational studies on the surgical treatment of gastric carcinoma within the last two decades. Overall, 6,035 patients with gastric cancer who had been registered in numerous German comprehensive surgical clinics and departments in the time periods 1986-1989, January through December 2002 and 2007-2009 were enrolled in this analysis. In particular, the study aimed to investigate the most important criteria and factors with an impact on the perioperative and early postoperative outcome including the effects on oncological long-term results. In addition to the advances in diagnostic procedures and surgical techniques, the impact of multimodal therapeutic concepts which have been established particularly in the third investigation period is emphasized.
Asunto(s)
Neoplasias Gástricas/cirugía , Estudios de Seguimiento , Gastrectomía/métodos , Gastrectomía/mortalidad , Alemania , Mortalidad Hospitalaria , Humanos , Estudios Multicéntricos como Asunto , Estadificación de Neoplasias , Observación , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND AND STUDY AIMS: This multicenter, prospective, country-wide quality-assurance study at more than 300 hospitals in Germany was designed to characterize and analyze the diagnostic accuracy of rectal endoscopic ultrasound (EUS) in the routine clinical staging of rectal carcinoma (depth of tumor infiltration). PATIENTS AND METHODS: Patients were surveyed between 1 January 2000 and 31 December 2008. Those who received neoadjuvant therapy after EUS were excluded. The correspondence between the EUS assessment of tumor depth (uT) and that determined by histology (pT) was calculated, and the influence of hospital volume upon the sensitivity, specificity, and positive and negative predictive values was investigated. RESULTS: At 384 hospitals providing care at all levels, 29â206 patients were included; of the 27â458 treated by surgical resection, EUS was performed for 12â235 (44.6â%). Of these, 7096 did not receive neoadjuvant radiochemotherapy, allowing a uT-pT comparison. The uT-pT correspondence was 64.7â% (95â% confidence interval [CI] 63.6â%â-â65.8â%); the frequency of understaging was 18â% (95â%CI 17.1â%â-â18.9â%) and that of overstaging was 17.3â% (95â%CI 16.4â%â-â18.2â%). The kappa coefficient was greatest in the category T1 (κ = 0.591). For T3 tumors κ was 0.468. The poorest correspondence was found for T2 and T4 tumors (κ = 0.367 and 0.321, respectively). A breakdown by hospital volume showed that the uT-pT correspondence was 63.2â% (95â%CI 61.5â%â-â64.9â%) for hospitals undertaking ≤ 10 EUS/year, 64.6â% (95â%CI 62.9â%â-â66.2â%) for doing 11â-â30 EUS/year, and 73.1â% (95â%CI 69.4â%â-â76.5â%) for those hospitals performing > 30 EUS/year. CONCLUSIONS: In clinical routine, the diagnostic accuracy of transrectal ultrasound in staging rectal carcinoma does not attain the very good results reported in the literature. Only in the hands of diagnosticians with a large case volume of rectal carcinoma patients can EUS lead to therapy-relevant decisions.
Asunto(s)
Carcinoma/diagnóstico por imagen , Endosonografía , Estadificación de Neoplasias/métodos , Neoplasias del Recto/diagnóstico por imagen , Carcinoma/patología , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Neoplasias del Recto/patología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The occurrence of peritoneal carcinomatosis after resection of colorectal carcinoma is still a major concern. In this study, we tested the cytostatic agent oxaliplatin delivered intraperitoneally and intravenously to prove whether it can significantly reduce intraperitoneal tumor growth. METHODS: Peritoneal tumor growth was experimentally induced with transfer of CC-531 colon cancer cells (5 x 10(6)) to the peritoneal surface of rats via laparotomy. Oxaliplatin was delivered either intraperitoneally or intravenously. In group A, oxaliplatin was administered directly after tumor cell transfer. While oxaliplatin was applied in group B on days 5, 10, and 15 after tumor cell implantation, in group C, it was administered on days 10, 15 and 20. The rats were sacrificed on day 30 after tumor cell transfer. Tumor weight, relative increase in tumor mass, volume of malignant ascites and the number of tumor nodes were determined. RESULTS: Oxaliplatin significantly inhibited tumor growth after direct (group A) and early postoperative application (group B) via the intraperitoneal route. The late postoperative administration of oxaliplatin (group C) did not cause a significant effect on peritoneal tumor growth as it did with the intravenous application mode in groups A, B, and C. CONCLUSIONS: In this experimental model, oxaliplatin was highly effective against intraperitoneal tumor spread but only with the intraperitoneal application route. Other cytostatic agents with different effector mechanisms should be combined with oxaliplatin to further increase the therapeutic efficacy of the favorable intraperitoneal treatment in subsequent studies testing, in addition, the effects on wound and anastomosis healing.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Adenocarcinoma , Animales , Carcinoma/patología , Carcinoma/cirugía , División Celular/efectos de los fármacos , Línea Celular Tumoral , Terapia Combinada , Modelos Animales de Enfermedad , Inyecciones Intravenosas , Tamaño de los Órganos/efectos de los fármacos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , RatasRESUMEN
BACKGROUND: The optimum regimen for advanced gastric cancer requires definition. This multicentre phase II study evaluated docetaxel-cisplatin combination in advanced gastric cancer. METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease received docetaxel plus cisplatin (75/75 mg/m(2)) every 21 days for up to 9 cycles. Endpoints included tumour response, time to progression, overall survival and toxicity. RESULTS: Of 113 patients recruited, 88 were completely evaluable. The median age was 58 years, and most patients had metastatic disease. The overall response rate was 29.6%. Five patients (5.7%) achieved a complete response and 21 patients (23.9%) had a partial response. Tumour control, including stable disease, was achieved in 57 patients (64.8%). The median time to progression and median overall survival time was 4.8 and 8.7 months, respectively. The major toxicity was haematological: 37.5% of patients experienced grade 3-4 neutropenia, whereas febrile neutropenia was observed in only 2% of patients. CONCLUSION: Docetaxel-cisplatin was active with a predictable and manageable toxicity profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Cisplatino/administración & dosificación , Docetaxel , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/secundario , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Estudios Prospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
AIMS: To assess the maximum tolerability of a combined therapy regimen of gemcitabine and docetaxel, and to evaluate tumour response rate, survival time and tolerability in patients receiving these agents for advanced pancreatic carcinoma. PATIENTS AND METHODS: Patients (n=68) with pancreatic carcinoma (advanced and/or unresectable tumour growth or histopathologically diagnosed metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study (n=43). Treatment during phase II of the study was continued until either complete tumour remission (CR), tumour progression, indicated clinically or by means of radiological imaging, or until unacceptable toxicity occurred. RESULTS: Phase I: the tolerability maximum of the combined agents was established at gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events. Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1-10). While CR was achieved in three of 43 patients (7%), in five further cases, partial remission (PR) was documented, amounting to an overall response rate (OR) of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43 subjects (39.5%), primary tumour progression was detected. The median survival time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients). These results were associated with a side-effect profile of moderate severity and acceptable quality of life (QOL). CONCLUSION: The combination of gemcitabine and docetaxel for chemotherapy in unresectable pancreatic carcinoma was well tolerated. Survival time and 1-year survival rate proved promising and the regimen appears suitable for further evaluation in a prospective phase-III study setting.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Taxoides/uso terapéutico , Adulto , Anciano , Carcinoma/mortalidad , Carcinoma/secundario , Desoxicitidina/uso terapéutico , Docetaxel , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Ribonucleótido Reductasas/antagonistas & inhibidores , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
INTRODUCTION: Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. METHODS: Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. RESULTS: Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic factor was R0-resection. In addition, prognosis after successful R0-resection is determined significantly by tumor site, stage of the tumor (according to UICC), T- and N-category. CONCLUSION: Resection of pancreatic and ampullary carcinoma according to oncological criteria with tumor-free margins can be considered a treatment option with curative intention and potential. Despite relative high postoperative morbidity, only a low mortality rate was observed. The 5-year survival-rate of 16.2 % in ductal pancreatic carcinoma underlines the demand for the development of effective multimodal therapeutic concepts. Interventions with primary palliative intention or resections with microscopically or macroscopically detectable tumor residual in situ lead to no significant or only marginal prolongation of survival time. Such interventions in patients with pancreatic carcinoma are no reasonable treatment alternative. They are of value only for treatment of tumor-associated complications and problems.
Asunto(s)
Ampolla Hepatopancreática , Carcinoma Ductal Pancreático/cirugía , Neoplasias del Conducto Colédoco/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Anastomosis Quirúrgica , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Femenino , Gastroenterostomía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Páncreas/patología , Pancreatectomía/métodos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias , Pronóstico , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen. PATIENTS AND METHODS: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m2 of gemcitabine and 25 mg/m2 of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer. RESULTS: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m2, and docetaxel, 45 and 40 mg/m2; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects > or = grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity. CONCLUSION: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Docetaxel , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Dimensión del Dolor , Neoplasias Pancreáticas/patología , Calidad de Vida , Índice de Severidad de la Enfermedad , Taxoides/administración & dosificación , Taxoides/efectos adversos , GemcitabinaRESUMEN
High local recurrence rates within the previous tumor bed or at the peritoneum remain an unsolved problem after surgical resection of malignant gastrointestinal tumors such as gastric, colorectal or pancreatic carcinoma. Currently, there are no standardized treatment protocols available for the prevention or treatment of peritoneal carcinomatosis. In a basic experimental trial, mitomycin, cisplatin, 5-FU, oxaliplatin and CPT-11 were used to prevent or treat peritoneal carcinomatosis induced in rats. Experiments were performed in three groups (n = 8 each) of animals plus two control groups. In the first group, Mitomycin, Cisplatin, 5-FU, Oxaliplatin and CPT-11 (n = 24 each) were applied directly following tumor cell implantation into the peritoneal cavity. In the second group, early postoperative intraperitoneal (i. p.) chemotherapy (day [d] 5, 10, 15 following surgical intervention for tumor cell transfer) was administered, whereas in the third group, late i. p. chemotherapy (d 15, 20, 25 following surgery) was given via a port-a-cath aiming for significant reduction of a visible, already established peritoneal carcinomatosis. Mitomycin and cisplatin were highly effective to prevent peritoneal carcinomatosis (direct application immediately after tumor cell transfer - 1 (st) treatment group). Using early postoperative i. p. chemotherapy (2 (nd) group), 5-FU and CPT-11 were shown to be significantly effective to reduce the intraperitoneal tumor spread. None of the cytostatic agents was able to decrease significantly an already generated peritoneal carcinomatosis (3 (rd) treatment group). The results suggest that novel chemotherapeutic drugs should be proven for their potential to alter peritoneal metastases of GI tumors i) in comparison with established drugs and ii) depending on the application time and mode.
Asunto(s)
Adenocarcinoma/prevención & control , Antibióticos Antineoplásicos/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Cisplatino/uso terapéutico , Fluorouracilo/uso terapéutico , Mitomicina/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/prevención & control , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/administración & dosificación , Cisplatino/administración & dosificación , Interpretación Estadística de Datos , Fluorouracilo/administración & dosificación , Neoplasias Gastrointestinales , Irinotecán , Masculino , Mitomicina/administración & dosificación , Trasplante de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Ratas , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Adulto , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Calidad de Vida , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Since there are currently no data available from a prospective trial, the primary objective of this prospective study was to investigate whether the rate of R0-liver resections without morbidity would be at least 50 % in patients with neoadjuvant chemotherapy for colorectal liver metastases. PATIENTS AND METHODS: 42 patients were treated with a biweekly FOLFOX regimen. Chemotherapy consisted of a 2-hour infusion of folinic acid (FOL) 500 mg/m2, followed by a 24-hour infusion of 5- fluorouracil (F) 2000 mg/m2 daily for two days. Oxaliplatin (OX) 85 mg/m 2 was given simultaneously with FOL. Treatment allocation was randomized with either 3 or 6 cycles for the final 30 patients. A liver resection was performed 2 to 5 weeks after the final infusion. RESULTS: An objective response was observed in 20 of 42 patients (response rate was 27 % higher after 6 cycles). Liver resection (R0) could be performed in 34 patients. Postoperative complications were reported in 14 patients (13 occurring within 30 days after resection) and severe complications in 5 cases (including two deaths after extended resection). Liver failure and persistent biliary fistula were the most frequently documented complications. There was no relevant difference in safety criteria between 3 and 6 applications. CONCLUSION: The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Terapia Neoadyuvante , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Hepatectomía , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos , Proyectos Piloto , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Following surgical resection of colorectal carcinoma, local recurrence in the tumor bed or in the mesentery remains a frequently encountered problem. Currently there are no recognized standard therapy protocols for the prevention of local recurrence or the treatment of peritoneal carcinomatosis. The aim of our trial was to investigate whether CPT-11 and oxaliplatin could decrease i.p. tumor growth in a basic experimental animal model. Experiments were performed on three groups of animals plus controls. In the first group, the cytostatic agents were applied directly following tumor cell implantation into the peritoneal cavity. In the second group, early postoperative i.p. chemotherapy (days 5, 10 and 15 following surgery) was administered. In the third group, late i.p. chemotherapy (days 15, 20 and 25 after tumor cell transfer) was administered with the intention of reducing a manifest peritoneal carcinomatosis. The trial also set out to describe any side effects observed following i.p. administration. The results indicated that CPT-11 and oxaliplatin were highly effective in reducing i.p. tumor spread after direct i.p intraoperative application. Intraperitoneal administration of CPT-11 or oxaliplatin also decreased i.p. tumor growth after early i.p. chemotherapy. CPT-11 was a little more effective with lower side effects. However, it was clear that it was not possible to treat a manifest peritoneal carcinomatosis in this way.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Carcinoma/prevención & control , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/prevención & control , Anestesia , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Carcinoma/patología , Inyecciones Intraperitoneales , Irinotecán , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Trasplante de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Neoplasias Peritoneales/patología , Ratas , Células Tumorales CultivadasRESUMEN
INTRODUCTION: We report our results of laparoscopic anterior transperitoneal adrenalectomy. PATIENTS: Between 4/1996 to 05/2001, a laparoscopic adrenalectomy was performed in 34 patients (median age 48 years). The adrenalectomy was performed transperitoneally (31 unilateral; 3 bilateral). The adrenaline level was measured in 7 patients with a pheochromocytoma. RESULTS: All tumors (mean size 3.5 cm; 0.4 to 8.0 cm) could be extirpated by laparoscopy. 9 pheochromocytomas; 9 cortisol producing tumors (one patient with a Carney's syndrome); 7 Conn's adenomas and 9 incidentalomas constituted these tumors. In the first third of the observation period, the surgery lasted 176 (95-270) minutes, in the last third 82 (50-130) minutes (p < 0,01). We postoperatively observed the following complications: one abdominal wall hematoma at a port-site and one edematous pancreatitis after alteration of the pancreatic tail. The adrenaline level continually rose from the beginning of surgery to the ligature of the suprarenal vein. CONCLUSION: Transperitoneal adrenalectomy in benign tumors (< 8 cm) is our method of choice. The resulting learning curve allowed the performance of adrenalectomy within an acceptable operative time and without significant blood loss. The transperitoneal technique is safe and well reproducible. The cosmetical results are convincing. We recommend an early ligature of the suprarenal vein in a pheochromocytoma.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Adenoma Corticosuprarrenal/cirugía , Laparoscopía/métodos , Síndromes Paraneoplásicos Endocrinos/cirugía , Feocromocitoma/cirugía , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Peritoneo/cirugía , Complicaciones Posoperatorias/etiologíaRESUMEN
Gastric stromal tumors are solitary, usually asymptomatic, lesions that can bleed, become obstructive, or even degenerate into malignant neoplasms. Therefore, their surgical excision is recommended. We report a technique for the successful resection of a stromal tumor of the posterior gastric wall using a transgastric approach. After the creation of a 12 mmHg pneumoperitoneum using a three-trocar technique, a 2-cm gastrostomy was performed; an 18-mm trocar was then positioned in the gastric lumen and secured with a pursestring suture. Next, an intragastric wedge resection of the posterior gastric wall was carried out under endoscopic guidance. Finally, the anterior gastric wall was closed using a linear stapler. Histopathological analysis showed a benign spindle cell tumor, which was excised in toto. Patient recovery was uneventful. This report supports previous data showing the feasibility of a laparoscopic transgastric approach for the resection of stromal tumors of the posterior gastric wall. It also underscores the synergy of laparoscopic and endoscopic procedures in minimally invasive gastric surgery.
Asunto(s)
Carcinoma/cirugía , Gastroscopía/métodos , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Anciano , Estudios de Factibilidad , Gastrostomía/métodos , Humanos , Masculino , Técnicas de SuturaRESUMEN
BACKGROUND AND AIMS: We compared the effectiveness and side effects of various cytostatic agents for use in perioperative intraperitoneal irrigation to prevent peritoneal carcinomatosis. METHODS: The adenocarcinoma cell line CC-531 was implanted during laparotomy at the mesenterial trunk of anesthetized male WAG rats. Direct perioperative intraperitoneal chemotherapy was performed after 5 min with either 5-fluorouracil, cisplatin, or mitomycin; controls received only tumor cells. The animals were inspected daily over 30 days for side effects. They were then killed, and the greater omentum and mesentery were resected, the tumor mass was examined for the presence of peritoneal carcinomatosis, and tumor nodules in the greater omentum and mesentery were counted. RESULTS: All the animals in the control group developed histologically confirmed peritoneal carcinomatosis. Animals receiving cisplatin or mitomycin by direct intraperitoneal perioperative chemotherapy showed no macroscopic or histological evidence of tumor growth. Two animals in the fluorouracil group had macroscopically and histologically manifest tumor growth; another animal showed only histological evidence of malignancy. Substantial side effects were noted in the cisplatin group, with all animals experiencing bleeding in the peritoneum and toxic necrotic reactions of the colon; two animals died of these side effects. CONCLUSION: Direct intraperitoneal chemotherapy with cisplatin or mitomycin prevents peritoneal carcinomatosis in experimental investigations.