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BACKGROUND AIMS: Dendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices. AIMS: From March 2010 to December 2023, 103 patients were enrolled in multiple clinical trials at the Immuno-Gene Therapy Factory at IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori". Six hundred forty-two doses were produced, and the manufacturing process was implemented to optimize production. Our study is a retrospective analysis focusing on the quality control results. METHODS: We retrospectively analyzed the results of the quality control tests carried out on each produced batch, evaluating viability, purity and phenotype of mDCs and their quality in terms of microbiological safety. The data obtained are given with median and interquartile range. RESULTS: The batches were found to be microbiologically safe in terms of sterility, mycoplasma, and endotoxins. An increase in DC maturation markers was found. The release criteria checks showed a high percentage of viability and purity was maintained during the production process. CONCLUSIONS: Our findings have confirmed that the measures implemented have ensured the safety of the products and have contributed to the establishing a robust "Pharmaceutical Quality System." This has enabled many safe mDCs to be produced for clinical trials.
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Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved.
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Neoplasias Colorrectales , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Quimioterapia Intraperitoneal Hipertérmica/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Terapia Combinada/métodos , Adulto , Estudios de CohortesRESUMEN
BACKGROUND: This study aimed to improve the understanding of the prognostic value of tumor mitotic rate (TMR) in cutaneous melanoma and assessed its significance as a predictor for overall, melanoma-specific, and recurrence-free survival. PATIENTS AND METHODS: This is a retrospective multicenter Italian cohort study of 13,016 patients diagnosed with and treated for invasive primary melanoma between 2005 and 2020 with median follow-up of 5.5 years. The survival probability was assessed by Kaplan-Meier method, hazard ratios (HRs), and corresponding 95% confidence interval (CI) of all-cause mortality and recurrence/death by multivariable Cox proportional hazards models. RESULTS: Higher dermal mitoses number was associated with decreased overall survival. Among patients with TMR 0/mm2 , 1/mm2 , 2/mm2 -3/mm2 , 4/mm2 -10/mm2 , and >10/mm2 , 5-year overall survival (OS) was 97.3%, 93.6%, 88.3%, 73.0%, and 60.9%, respectively. In multivariate analyses, compared to TMR of 0/mm2 , HRs for all-cause mortality were 1.35 (95% CI, 1.08-1.68), 1.70 (95% CI, 1.40-2.07), 2.04 (95% CI, 1.67-2.49), and 2.39 (95% CI, 1.90-3.00) for 1 mitoses/mm2 , 2 mitoses/mm2 -3 mitoses/mm2 , 4 mitoses/mm2 -10 mitoses/mm2 , and >10 mitoses/mm2 , respectively. A similar increase in risks was observed in melanoma-specific survival (MSS) and recurrence-free survival (RFS). The HRs for MSS and RFS for the highest compared to the lowest TMR category were 3.01 (95% CI, 2.20-4.11) and 2.26 (95% CI, 1.88-2.73), respectively. Sentinel lymph-node biopsy positivity was significantly associated with TMR increase even with adjustment for several potential confounders. CONCLUSIONS: A clear association was demonstrated between an increasing TMR and decreased OS, MSS, and RFS, suggesting a reconsideration of TMR prognostic role for future inclusion in the melanoma staging system. PLAIN LANGUAGE SUMMARY: The 8th American Joint Committee on Cancer for melanoma staging removed tumor mitotic rate (TMR) from the staging criteria for T1 melanomas, giving way to ulceration and tumor thickness as stronger prognostic predictors. However, it is still recommended that TMR should be assessed and recorded in all primary invasive melanomas. In a large retrospective multicenter study on primary invasive melanomas, we investigated the prognostic value of TMR to assess its significance as survival predictor. Our results showed a clear association between increasing TMR and decreased patients' survival, suggesting that TMR should be considered for inclusion in the melanoma staging system.
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Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , Pronóstico , Estudios de Cohortes , Estadificación de Neoplasias , Biopsia del Ganglio Linfático Centinela , Estudios Retrospectivos , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.
Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.
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Electroquimioterapia , Melanoma , Humanos , Indicadores de Calidad de la Atención de Salud , Consenso , Benchmarking , Técnica DelphiRESUMEN
BACKGROUND: The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. METHODS: A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. RESULTS: The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS. CONCLUSION: The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization.
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Linfadenopatía , Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/patología , Pronóstico , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Carga TumoralRESUMEN
BACKGROUND: Although gallstone disease increases with aging, elderly patients are less likely to undergo cholecystectomy. This is because age itself is a negative predictor after cholecystectomy. The ACS-NSQIP risk calculator can therefore help surgeons decide whether to operate or not. However, little is known about the accuracy of this model outside the ACS National Surgical Quality Improvement Program. The aim of the present study is to evaluate the ability of the ACS-NSQIP model to predict the clinical outcomes of patients aged 80 years or older undergoing elective or emergency cholecystectomy. STUDY DESIGN: The study focused on 263 patients over 80 years of age operated on between 2010 and 2019: 174 were treated as emergencies because of acute cholecystitis (66.2%). Outcomes evaluated are those predicted by the ACS-NSQIP calculator within 30 days of surgery. The ACS-NSQIP model was tested for both discrimination and calibration. Differences among observed and expected outcomes were evaluated. RESULTS: When considering all patients, the discrimination of mortality was very high, as it was that of severe complications. Considering only the elective cholecystectomies, the discrimination capacity of ACS-NSQIP risk calculator has consistently worsened in each outcome while it remains high considering the emergency cholecystectomies. In the evaluation of the emergency cholecystectomy, the model showed a very high discriminatory ability and, more importantly, it showed an excellent calibration. Comparisons between main outcomes showed small or even negligible differences between observed and expected values. CONCLUSION: The results of the present study suggest that clinical decisions on cholecystectomy in a patient aged 80 years or older should be assisted through the ACS-NSQIP model.
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Octogenarios , Complicaciones Posoperatorias , Anciano , Anciano de 80 o más Años , Colecistectomía/efectos adversos , Predicción , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Mejoramiento de la Calidad , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
BACKGROUND: In this study, we report our experience of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC), focusing on the factors affecting survival. METHODS: All patients with surgically treated PC from colorectal cancer and with no involvement of other organs referred to our institute from March 2005 to December 2017 were included in the analysis. RESULTS: Thirty-eight patients underwent CRS-HIPEC, and all had a completeness of cytoreduction score of 0 (CC0). The median operating time was 645 min (interquartile range [IQR] 565-710). Five patients (13.1%) had Clavien-Dindo grade > 2 postoperative complications. Median overall survival (OS) was 60 months. In the Cox regression for OS, calculated on the CRS-HIPEC group, the peritoneal cancer index (PCI) > 6 (hazard ratio [HR] 4.48, IQR 1.68-11.9, P = 0.003) and significant nodal involvement (N2) (HR 3.89, IQR 1.50-10.1, P = 0.005) were independent prognostic factors. Median disease-free survival (DFS) was 16 months. Only N2 (HR 2.44, IQR 1.11-5.36, P = 0.027) was a significantly negative prognostic factor for DFS in multivariate analysis. CONCLUSIONS: CRS-HIPEC can substantially improve survival. However, patients with high PCI (PCI > 6) and significant nodal involvement (N2) may not benefit from the procedure.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/terapia , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Neoplasias Peritoneales/terapia , Anciano , Neoplasias Colorrectales/patología , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/secundario , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC. MATERIALS/METHODS: This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34-74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC. RESULTS: For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1-28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1-49 months). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/mortalidad , Hipertermia Inducida , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Adulto , Anciano , Cisplatino/administración & dosificación , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Doxorrubicina/administración & dosificación , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intraperitoneales , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Incidence of gallstones in those aged ≥ 80 years is as high as 38%-53%. The decision-making process to select those oldest old patients who could benefit from cholecystectomy is challenging. AIM: To assess the risk of morbidity of the "oldest-old" patients treated with cholecystectomy in order to provide useful data that could help surgeons in the decision-making process leading to surgery in this population. METHODS: A retrospective study was conducted between 2010 and 2019. Perioperative variables were collected and compared between patients who had postoperative complications. A model was created and tested to predict severe postoperative morbidity. RESULTS: The 269 patients were included in the study (193 complicated). The 9.7% of complications were grade 3 or 4 according to the Clavien-Dindo classification. Bilirubin levels were lower in patients who did not have any postoperative complications. American Society of Anesthesiologists scale 4 patients, performing a choledocholithotomy and bilirubin levels were associated with Clavien-Dindo > 2 complications (P < 0.001). The decision curve analysis showed that the proposed model had a higher net benefit than the treating all/none options between threshold probabilities of 11% and 32% of developing a severe complication. CONCLUSION: Patients with American Society of Anesthesiologists scale 4, higher level of bilirubin and need of choledocholithotomy are at the highest risk of a severely complicated postoperative course. Alternative endoscopic or percutaneous treatments should be considered in this subgroup of octogenarians.
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Castleman's Disease is a rare tumour involving lymph node tissues; a case of benign localized disease and a case of rapid progressive multicentric disease are reported. Case report 1: A 19-year-old man presented with four months of hypogastric and left iliac pain. Castleman's Disease was suspected after CT-scan. A CT-guided fine-needle biopsy of the lesion was performed revealing hyaline vascular type Castleman's Disease. The patient underwent open surgery with radical excision of the lesion. No adjuvant therapy was performed after surgery. The patient is alive and disease-free after 24 months. Case report 2: A 58-year-old woman presented with a right axillary palpable lymph node and vague abdominal discomfort. Abdomen CT demonstrated hepatosplenomegaly associated with adenopathy at the hepatic hilus and splenic hilus; dilatation of intra-hepatic biliary ducts was present. The axillary node was excised, the mass at hepatic hilus was biopsied. The diagnosis was Castleman's Disease in both sites. In course of steroid therapy retroperitoneal multiple nodes appeared associated with fast-progressive mechanic jaundice and liver failure. Progressive multi-organ failure arose within 1 week, with irreversible clinical worsening to death.
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Enfermedad de Castleman/diagnóstico , Biopsia con Aguja Fina , Enfermedad de Castleman/diagnóstico por imagen , Enfermedad de Castleman/patología , Enfermedad de Castleman/cirugía , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8-33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16-61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.
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Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Quimioterapia/estadística & datos numéricos , Melanoma/terapia , Radioterapia/estadística & datos numéricos , Adulto , Anciano , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/efectos adversos , Terapia Combinada , Femenino , Hemocianinas/uso terapéutico , Humanos , Hipersensibilidad Tardía/etiología , Hipersensibilidad Tardía/inmunología , Interleucina-2/uso terapéutico , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del Tratamiento , VacunaciónRESUMEN
BACKGROUND AND AIMS: Survival rates of patients with stage IV melanoma are poor: Median survival is 7-8 months and 5-year survival rates about 5%. There is no agreement on the role of surgery at this stage. Most patients with metastatic melanoma are not able to undergo resection and usually are sent to systemic chemo- and immunotherapy. PATIENTS AND METHODS: Eighty-four patients operated on for stage IV melanoma were evaluated. Of them, 61.9% were submitted to reiterative surgery with 168 operations and 182 surgical procedures overall. A total of 90.5% was submitted to adjuvant therapies according to aggressive and reiterated schedules: chemotherapy, immunotherapy, dendritic cells vaccine, infusion of tumor infiltrating lymphocytes, local therapies as electrochemotherapy. RESULTS: The mean overall survival (Kaplan-Meier) was 56.7 months (1 year: 72.1%, 3 years: 46.5%, 5 years: 23.16%). The survival of reiterative surgery was significatively longer than single surgery (62.7 vs 42.4 months, median 50.9 vs 16.0), p = 0.03. Multivariated Cox analysis was performed for disease-free interval, repeated surgery, adjuvant therapies, and site of metastasis according to the American Joint Committee on Cancer: Reiterative surgery was shown as an independent prognostic factor (p < 0.05). CONCLUSION: Metastatic resection associated with adjuvant therapy may improve overall survival and, in some instances, can provide long-term survival, whatever site and numbers of metastasis. In our series, reiterative surgery was more significatively efficient in improving survival than single-time surgery.
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Melanoma/mortalidad , Melanoma/cirugía , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to evaluate the role of robotic total splenectomy for splenomegaly, comparing this approach with the laparoscopic technique. METHODS: We conducted a retrospective review of all patients who underwent minimally invasive splenectomy for splenomegaly (maximum splenic diameter>15â¯cm) at our institution between 2000 and 2017. RESULTS: A total of 39 patients (27 laparoscopic vs 12 robotic splenectomies) were included in the study. Operative time was significantly longer in the robotic group (270â¯min vs 180â¯min, pâ¯=â¯0.007). Median intraoperative blood loss was 350â¯ml for laparoscopic procedures while it was 100â¯ml for the robotic ones (pâ¯=â¯0.032). Conversion to open surgery was required in 4 cases of laparoscopic splenectomy while no conversion were registered in the robotic group. No significant differences were seen in postoperative morbidity and mortality between the two groups. CONCLUSIONS: Robotic splenectomy for splenomegaly is associated with less blood loss and longer operative times than the laparoscopic procedure.
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Laparoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Esplenectomía/métodos , Esplenomegalia/cirugía , Adulto , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Conversión a Cirugía Abierta/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases. A phase II randomised trial showed an advantage OS of a DC vaccine over a tumour cell-based vaccine (2-year OS 72% vs31%, respectively). Given that there is no standard therapy after surgical resection of single metastases, we planned a study to compare vaccination with DCs pulsed with autologous tumour lysate versus follow-up. METHODS AND ANALYSIS: This is a randomised phase II trial in patients with resected stage III/IV melanoma. Assuming a median relapse-free survival (RFS) of 7.0 months for the standard group and 11.7 months for the experimental arm (HR 0.60), with a two-sided tailed alpha of 0.10, 60 patients per arm must be recruited. An interim futility analysis will be performed at 18 months. The DC vaccine, produced in accordance with Good Manufacturing Practice guidelines, consists of autologous DCs loaded with autologous tumour lysate and injected intradermally near lymph nodes. Vaccine doses will be administered every 4 weeks for six vaccinations and will be followed by 3 million unit /day of interleukin-2 for 5 days. Tumour restaging, blood sampling for immunological biomarkers and DTH testing will be performed every 12 weeks. ETHICS AND DISSEMINATION: The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethics Committee for review. The local Ethics Committee and the Italian Medicines Agency approved the protocol (EudraCT code no.2014-005123-27). Results will be published in a peer-reviewed international scientific journal. TRIAL REGISTRATION NUMBER: 2014-005123-27.
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Vacunas contra el Cáncer , Extractos Celulares/uso terapéutico , Células Dendríticas/inmunología , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Antineoplásicos/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Células Dendríticas/trasplante , Humanos , Interleucina-2/uso terapéutico , Melanoma/patología , Melanoma/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Trasplante AutólogoRESUMEN
Peritoneal carcinomatosis is the first cause of death after surgery for abdominal cancer, with a mean survival of 7 months. In selected patients, aggressive cytoreductive therapy combined with hyperthermic intraperitoneal chemotherapy my improve medium to long-term survival. Over the period from 2004 to January 2006, 86 patients were operated on for peritoneal carcinomatosis at the Division of Surgical Oncology, Forli, Italy. Thirteen of them were submitted to hyperthermic chemotherapy. The authors present their preliminary experience with the treatment of colorectal carcinosis by 30-min hyperthermic (41.5-42 degrees C intraperitoneal perfusion with oxaliplatin (400 mg/sq.m.) and intravenous 5-FU (400 mg/sq.m.) after complete cytoreductive surgery. The average surgical time was 606 min (range: 380-765). No intraoperative complications occurred, but 4 cases of major postoperative morbidity were reported, one of which requiring surgery. One patient died 5 months postoperatively due to lung metastases. The remaining patients are alive and free from peritoneal disease.
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Antineoplásicos/uso terapéutico , Carcinoma/terapia , Quimioterapia del Cáncer por Perfusión Regional/métodos , Neoplasias Colorrectales/terapia , Hipertermia Inducida , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/terapia , Anciano , Antineoplásicos/administración & dosificación , Carcinoma/secundario , Neoplasias Colorrectales/patología , Femenino , Humanos , Infusiones Parenterales , Inyecciones Intraarteriales , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.
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Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Adenocarcinoma/secundario , Adenoma de las Glándulas Sudoríparas/patología , Glándulas Ecrinas/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adenocarcinoma/cirugía , Adenoma de las Glándulas Sudoríparas/cirugía , Diagnóstico Diferencial , Glándulas Ecrinas/cirugía , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sudoríparas/cirugíaRESUMEN
A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.