Median Global Survival Research Articles

#2757 Clinical course and prognostic factors in amyloidosis

Abstract Background and Aims Early diagnosis and specific therapy are crucial for the prognosis of patients with systemic amyloidosis. The aim of this single-center retrospective study was to evaluate the clinical course and identify prognostic factors associated with survival in a large cohort of patients from the Regional Reference Center “Gemelli Isola” in Rome, Italy. Method A total of 244 patients with amyloidosis were studied, including 100 with AL (63 M, 37 F, mean age 64 ± 13 yrs), 18 with AA (3 M, 15 F, mean age 57 ± 21 yrs), 9 with amyloidosis due to myeloma (MM) (5 M, 4 F, mean age 65 ± 15 yrs), 69 with ATTR mutant (38 M, 31 F, mean age 63 ± 15 yrs), 33 with ATTR wild-type (31 M, 2 F, mean age of 70 ± 10 yrs) 2 with Apolipoprotein (1 M, 1 F, mean age 60 yrs), and 15 unclassified amyloidosis (AX) (9 M, 6 F, mean age 63 ± 9 yrs). We considered several parameters, comprising gender, age, type of amyloidosis, time interval between disease onset and diagnosis, clinical signs and symptoms at onset and diagnosis, biochemical parameters, score of renal involvement (RI) (absent, proteinuria, nephrotic syndrome, and eGFR < 60 ml/min), score of cardiac involvement (CI) (absent, hypertrophic cardiopathy, dilated cardiopathy, arrhythmias and heart failure) at onset, diagnosis, and follow-up (FU). Renal outcome was defined as renal replacement therapy (RRT) initiation. The diagnosis of amyloidosis was histologically confirmed in all patients by Congo red stain, immunohistochemical classification and specific diagnostic criteria. Data were collected at diagnosis and retrieved dating back to the clinical onset. The impact of treatment was evaluated, in terms of clinical course and prognosis. Results Regardless of the amyloidosis type, between the onset and diagnosis clinical signs and symptoms significantly worsened and the involvement of affected organs increased. The median time from disease onset to diagnosis was 12 months for AL, AX, and MM, and 36 and 37 months for AA and ATTR. RI increased in all patients, from 47% at onset to 65% at diagnosis, and 71% during FU (p < 0.001). In the AL subgroup an eGFR < 60 ml/min was identified in 16% of patients at onset, 37% at diagnosis and 51% at FU (p < 0.001). As expected, in the mutant ATTR group RI was identified in only a small proportion of patients and an eGFR < 60 ml/min was found only in 2% of patients at onset and at diagnosis and in 6% at FU. CI was observed in 77% of all patients at onset, 88% at diagnosis and 98% at FU (p < 0.001). In the AL subgroup, at onset there was a high prevalence of hypertrophic cardiopathy (65%), while at FU there was a significant increase in the prevalence of heart failure (51%) (p < 0.001). In the mutant ATTR group, at onset, hypertrophic cardiopathy was present in 80% of patients while, at FU, heart failure was present in 64%. The median global survival time was 8 years (IC 95%, 7-12 yrs). RRT was started in 28% of patients. Survival curves according to renal and cardiac scores are shown in Fig. 1. Mortality at 6 years was statistically significative in patients with RI (p < 0.005). Survival curve according to renal or cardiac vs RI and CI is shown in Fig. 2. The univariate analysis demonstrated that progressive cardiac impairment from onset to FU, the number of organs involved, serum creatinine, albumin and eGFR had a significant impact on survival (HR of 18.46, CI 95% = 2.57-132.79; HR = 1.33, CI 95% = 1.09-1.62; HR = 1.47, CI 95% = 1.05-2.05; HR = 0.37, CI 95% = 0.24-0.56; HR = 0.99, CI 95% = 0.98-0.99). The multivariate analysis was based on the ‘forward stepwise’ method to select the significant predictors of mortality. The number of organs involved, age at onset, CI at onset, albumin and progressive worsening of CI from onset to FU, significantly impacted on survival (HR = 1.30, CI 95% = 1.02-1.65, p = 0.031, HR = 1.03, CI 95% = 1.01-1.05; HR = 2.08, CI 95% = 1.20-3.60; HR = 0.33, CI 95% = 0.21-0.53; HR = 21.40, CI 95% = 2.95-155.14). Conclusion The diagnosis of amyloidosis is often delayed. Prognosis is significantly influenced by the degree of CI and RI, serum albumin, age at onset and the number of organs involved. Better diagnostic accuracy and the availability of novel therapies have however significantly improved survival rates.

Predictors of survival and technical success of bronchoscopic interventions in malignant airway obstruction.

BackgroundMalignant airway obstruction (MAO) leads to quality of life impairment and increased mortality. Interventional bronchoscopy allows airway patency restoring, leading to a better survival. We investigated predictors of survival and successful bronchoscopic intervention among MAO patients.MethodsThis observational prospective study enrolled 100 patients who were newly diagnosed with MAO. Survival was estimated with Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses were performed using Cox proportional hazard models. Univariate and multivariate logistic regression were used for odds ratio calculation.ResultsA proportion of 73% of the patients were male with a median age was 62.5 years (range, 21–88 years). Lung cancer was the most common primary malignancy (74%). The majority had single (61%), endoluminal (62%) lesions and were classified as grade III in Myer Cotton scale (57%). The most used techniques comprised mechanical debulking (n=81) and laser therapy (n=68). Twenty-two airway stents were placed. While eleven patients were considered untreatable, technical success was achieved in 78%. Haemorrhage was the most common acute complication (16%). No deaths occurred as a result of the procedure. Median global survival was 8 months. Adjusting for age and Eastern Cooperative Oncology Group Performance Status (ECOG), extrinsic compression or mixed airway obstructions [hazard ratio (HR) =2.075; P=0.012], successful bronchoscopic intervention (HR =0.468; P=0.025) and initiation of cancer treatment (HR =0.373; P=0.006) were independent predictors of survival. The absence of distal airway patency on thoracic CT was independently associated with failure of the intervention [odds ratio (OR) =0.013; P<0.001].ConclusionsInterventional bronchoscopy has proven to be an efficient and safe strategy to manage MAO patients. The patients who benefit the most in terms of survival are those with purely endoluminal lesions, in whom technical success was achieved and those whose cancer-specific treatment was initiated. Distal airway patency on thoracic CT predicts the technical success of bronchoscopic intervention.

Melanoma cutáneo en Uruguay: características clínico-epidemiológicas y sobrevida en cohorte de pacientes de dos centros de referencia en el período 2008-2017

Cutaneous melanoma is the tumour whose incidence has increased the most in recent years. This condition is highly lethal in advanced stages. In our country the annual average of cases adds up to 129 in men and 117 in women, there being 50 and 30 respectively, every year.Objective: to describe and analyse the clinical and epidemiological profile and survival in a cohort of patients who are carriers of cutaneous melanoma and were assisted in two reference centers in Montevideo between 2008 and 2017.Methods: we conducted a descriptive, retrospective, observational study of historical cohorts, based on a review of the medical records in patients with a diagnosis of cutaneous melanoma assisted in the Oncology Service of the University Hospital and the Skin Oncology Unit of the National Cancer Institute between 2008 and 2017, with a follow-up until March 31, 2018.Results: 173 pacientes were analysed, median age was 61.2 years old (14-89), 50.3% were men and 49.7% were women. Nodular anatomo-clinical presentation was the most frequent form (32.7%), followed by superficial spreading (28.9%), other forms being less frequent. Median global survival was not achieved, global survival after 5 years being 68.5% and 54.5% after 10 years. Median global survival in Stage 4 was 12 months (IC 95% 8.5-21.5).Conclusions: the results in our series are similar to those reported internationally, in terms of global survival, the same as in most of the clinical an epidemiological characteristics. This is the first study with a cutaneous melanoma survival report in our country.

SUN-218 Analysis of ATRX and ZNRF3 Expression and Copy Number Variation in a Pediatric and Adult Cohort with Adrenocortical Tumors

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 1 to 2 cases per million/year in adults and with a global survival rate of less than 40% in 5 years. ACC diagnosis was based on Weiss criteria for adult patients. Pediatric patients with adrenocortical tumors (PAT), in general, are associated with better survival in most cases, and the malignant disease is established when local or distant metastases are found. The integrated and extensive genomic-molecular characterization of ACC has resulted in a better understanding of its pathophysiology. Some studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenal tumorigenesis in pediatric and adult patients with PAT and ACC, respectively. However, these data have not been validated in a Brazilian cohort with a high prevalence of the TP53 germline R337H mutation. Objectives: We aimed to evaluate the ATRX and ZNRF3 expression and copy number variation in a Brazilian cohort of patients with PAT and adults with ACC from a tertiary center. Patients and Methods: 34 adults (19 women - 56%) with median age 49 years old (range 18-83) and twelve pediatric patients (7 girls - 58%) with median age three years old (0.8-15 years old) were included in this study. The epidemiological data, clinical presentation, hormonal data, radiological imaging, and genetic background for TP53 were retrospectively evaluated. MLPA and RT-PCR were employed to evaluate the copy number variation and the gene expression, respectively, of ATRX and ZNRF3 in tumor tissues. Results: Adult group: Seven patients out of 27 (25.9%) presented the pathogenic germline mutation pR337H onTP53. 20 patients (58.8%) presented metastasis, and 19 (55%) had a fatal outcome. The median global survival was 17.23 months (0.6-185.8 m). Pediatric group: 10 patients (83.3%) presented the pathogenic germline mutation p.R337H on TP53. Four patients presented metastasis and only two had a fatal outcome. The median global survival was 42.4months (6.63-125.5m). All tumors were functional. Molecular results: Three out of 33 adult patients (9%), and 2 out of 12 (16.6%) pediatric patients presented deletion on ATRX. Four out of 25 adults (16%) and 2 out of 12 pediatric (16.6%) patients showed deletion on ZNRF3. There was no correlation between ATRX and ZNRF3 expressions or deletions with the overall survival rate (p>0.05). The decrease in the ATRX expression was associated with the presence of TP53 germline mutation in pediatric and adult cohorts (p 0.028). Conclusion: We confirmed the presence of alterations on ATRX and ZNRF3 genes in both cohort (adult and pediatric tumors). These results differ from the previous studies, which demonstrated ATRX and ZNRF3 alterations were present in pediatric and adult tumors, respectively. However, prospective studies with larger cohorts are necessary to confirm the prognostic value of ATRX and ZNRF3 genes in PAT and adults with ACC.

Laparoscopic versus open liver resection for hepatocellular carcinoma in a UK population: a single centre experience

Aims: Since mid-1970s liver cancer incidence rate increased overall in Great Britain, being now the 18th most common cancer in England. The aim of this study was to analyse our ten-years results related to hepatocellular carcinoma (HCC) treatment in a UK population, comparing surgical and oncologic outcomes obtained by laparoscopic versus open approach. Methods: Between January 2005 and December 2014, sixty-two hepatic resection for HCC were performed at our Institution. Patients were divided in two groups: A- patients undergoing open liver resection (OLR), B- patients undergoing laparoscopic liver resection (LLR). Intraoperative, postoperative and oncologic outcomes were analysed and compared between the two groups. A subgroup analysis of patients with lesions >5 cm was performed to assess the impact of size on outcomes and patients selection to the laparoscopic approach. Results: Twenty-six OLR and thirty-six LLR were performed. There were no statistical differences in demographic parameters, incidence of cirrhosis, operative time, margin status, perioperative mortality rate and DFS between the two groups. The median size of the tumours was significantly higher in the open group 8.6 cm vs 5.5 cm (p=0.035). Patients undergoing LLR had lower blood loss (p=0.033), shorter high dependency unit (p=0.005) and general hospital-stay (p=0.001) and lower 30-days morbidity rate (p=0.003). Median global survival was 58 months: surprising LLR did positively influenced OS (p=0.047), with a median survival of 68 months versus the 38 months accomplished with OLR. Laparoscopic approach confirmed favourable outcomes in both perioperative and on oncologic fields also for tumours major than 5 cm in size. Conclusions: Despite the lower incidence of liver cancer in UK, an increasing number of HCC has been noticed since the early 1990s. Our ten-years experience demonstrates that LLR for HCC is feasible and safe, conferring the widely accepted benefits arising from a mini-invasive approach, and ensuring both perioperative and oncologic favourable outcomes.

PCN32 - Impact on Illness-Free Survival (IFS) and Global Survival (GS) of the Starting Time of Adjuvant Breast Cancer

To determine if the starting time of chemotherapy influences on illness-free survival and general survival in a cohort of Mexican patients with breast cancer. A prospective study over 5 years was performed on 88 women with breast cancer from the National Medical Centre “La Raza” of the Mexican Institute of Social Security (IMSS) with the following characteristics: stages I-III and positive criteria for adjuvant chemotherapy. The time range for the chemotherapy administration was 0 to 2, 3 and >4 months. The analysis was performed regarding chemotherapy administration time interval using a Kaplan-Meier estimator. The Cox model was adjusted to see the relationships between the global survival and the oestrogen and progesterone hormone receptor variables and HER2/NEU as well as their basal characteristics. For both IFS and GS there was a significantly statistical difference on the survival distributions related to starting time of chemotherapy which had a higher probability from a range of 0 to 2 months (median GS 59 months median IFS 49 months; p-value<0.001). Regarding general survival, the hormonal receptors for oestrogen, progesterone and HER2/NEU do not influence on the Cox model (p-value=0.137, 0.823, 0.524 respectively); for the Cox model with basal characteristics, age, pathological state and time interval between surgery and chemotherapy influenced significantly on GS (p-value<0.05) The probability of survival for IFS and GS improve when chemotherapy is administered within the first 2 months after surgery. Also, there was a greater risk for GS when time interval between surgery and chemotherapy was prolonged. This delay for the starting time of chemotherapy will impact without a doubt in the health systems´ economy, generating more expenses for attention.

P-0259 - Hepatic Metastasectomy and Chemotherapy in Colorectal Cancer Treatment

Background: The best treatment for colorectal hepatic metastases is hepatic metastasectomy. The metastases resectability is associated with survival and should be considered in the therapeutic management in stage IV patients. Perioperative chemotherapy may be associated with major survival in these patients. Methods: Retrospective review of all patients who had hepatic metastasectomy at a central hospital from the years of 2007 to 2012. Survival analysis was performed by using the Kaplan-Meier method. Results: We have reviewed 139 cases, with a mean age of 62 years old [20-85]. 73% of patients had colon cancer and 27% rectal cancer. 14% of all patients didnt receive any chemotherapy. 2 patients receive neo-adjuvant chemotherapy, 58 patients had adjuvant chemotherapy and 46 had both neo-adjuvant and adjuvant chemotherapy. 32 patients responded to the neo-adjuvant chemotherapy. The neo-adjuvant chemotherapy scheme more often used was FOLFIRI with bevacizumab. From de 46 patients who had neo-adjuvant chemotherapy followed by surgery and adjuvant chemotherapy, 40 received the same chemotherapy scheme. FOLFOX was the most used scheme in adjuvant chemotherapy. 114 patients had R0 surgery. Today, 35% of patients have no evidence of disease, 27% are dead; 12% are receiving palliative chemotherapy, 8% are receiving adjuvant chemotherapy; 6% are in supportive care and 12% were lost from follow-up. The 1-year relapse free survival was 60% and the 5-year relapse free survival was 22%. The median relapse-free survival was 17 months [CI95% 13-21]. The 1-year global survival was 85% and the 5-year global survival was 39%. The median global survival was 38 months [CI95% 26-50]. Conclusion: In this review the hepatic metastases resections had low mortality and morbidity, so it should be considered in selected patients. The chemotherapy schemes were well tolerated permitting surgery and may have prolonged relapse-free intervals, or even cure.

Diagnosis of incidental gallbladder cancer after laparoscopic cholecystectomy: our experience

BackgroundGallbladder carcinoma is a rare high malignancy neoplasm. The incidence of intra or post-operative incidental gallbladder carcinoma diagnosis is estimated between 0,2 and 2,8%. Primary aim of our study is to evaluate incidental gallbladder carcinoma's incidence in our experience.MethodsWe retrospectively reviewed our Surgery Division's experience about the totality of laparoscopic cholecystectomies with post-operative histological evidence of incidental gallbladder cancer. We evaluated patients' characteristics, surgical related variables, histological response, surgivcal radicalization characteristics and surgical outcome.ResultsIn the considered sample we observed 7 accidental gallbladder adenocarcinomas in post-operative histological examination. Pathological results were:1 pT1b N0 (G1), 2 pT2 N0 (G2), 2 pT2 N1 (G3b), 2 pT3 N1 (G3b) (Table 1). In 5 cases we performed neoplasm radicalization surgery with standard procedure revision. Two patients died before radicalization. Median global survival was 34 months.ConclusionWith the increase of laparoscopic cholecystectomies both elective and urgent performed in our centre we observed also an increase of incidentally diagnosed gallbladder neoplasms. Early diagnosis, meticulous peri-operative study and accurate surgical strategy are essential factors to obtain good results in incidental gallbladder cancer.

Immunohistochemical expression of cyclooxygenase-2 in patients with advanced cancer of the larynx who have undergone induction chemotherapy with the intention of preserving phonation

Cyclooxygenase-2 (COX2) is an enzyme that plays a role in different stages of the carcinogenic process and has prognostic and predictive values that have not yet been established. The objective of this study was to evaluate the role of COX2 overexpression in advanced squamous cell carcinoma of the larynx that has been treated with a phonation conservation protocol. This study included a retrospective analysis of 59 patients with resectable tumours that were treated with chemotherapy (CT) and/or radiation therapy (RT). The expression levels of COX2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor (VEGFR-2) in collected biopsy specimens were determined via immunohistochemistry. Forty-four percent of the included samples demonstrated overexpression of COX2. In the statistical analysis, COX2 overexpression did not correlate with other clinical or treatment efficacy prognostic factors; however, the median global survival (OS) of patients whose tumours expressed COX2 was 79 months, whereas COX2-negative patients had a median OS of only 38 months, although this finding did not reach statistical significance. The other analysed biological parameters did not demonstrate a significant relationship with COX2. COX2 overexpression was a common finding in our study. The results obtained did not reveal relationships with established prognostic categories; however, the difference in survival between patients with and without COX2 expression justifies the need for future prospective studies that utilise a larger patient sample size.

Influence of the in situ component in 389 infiltrating ductal breast carcinomas

Our aim was to evaluate and compare lymph node involvement, as well as disease-free survival (DFS) and overall survival (OS), between infiltrating ductal carcinoma with (group 1) and without (group 2) intraductal carcinoma component in order to determine the prognostic value of the intraductal component. Data from 389 cases of infiltrating ductal carcinoma of the breast were included in the study by means of reviewing medical charts and pathology slides. There was no statistically significant difference between both groups regarding node status. The 5-year DFS rate was 90.7% in group 1 and 81.8% in group 2 (p=0.014), with a median follow-up of 73.2months (95% CI 68.3-77.4). There was no statistically significant difference in 5-year OS between groups (98% group 1 vs. 93% group 2) with a median global survival of 134months (95% CI 131-137). The presence of intraductal component in the infiltrating carcinoma seems to increase DFS and may be an independent and favorable prognostic factor for breast cancer.

Efectividad y seguridad del régimen FLAG-IDA en leucemias agudas resistentes o recidivantes

ObjectiveTo evaluate the effectiveness and safety of the FLAG-IDA regimen in patients with acute refractory and/or recurrent leukaemia. MethodDescriptive, retrospective, observational study of the clinical histories of patients with the FLAG-IDA regimen during the period of 2005-2010. Effectiveness was measured using objective response, progression-free interval, and global survival. Safety was measured using the NCI classification system of common toxicity criteria for adverse events. ResultsWe registered 12 patients (52.17±8.26 years in women, and 54.83±7.22 years in men), 11 cases were acute myeloid leukaemia (5 refractory, 3 in recurrence, 1 secondary to chronic refractory myeloid leukaemia (CML) and 2 secondary to myelodysplastic syndrome (MDS), one of which was refractory and the other had not been previously treated) and one case was acute refractory lymphoblastic leukaemia (ALL). Six patients (50%) reached a complete response (CR). One patient reached a partial response (PR), which was followed by another protocol that produced a CR, two died due to disease progression, and three due to secondary complications from treatment.The progression-free interval for patients that reached a CR was 24.38 weeks (6 months). Median global survival was 8.4 weeks.Mean time needed for the recovery of neutropenia was 23 and 37 days in the first and second cycle, respectively. The mean time required for recuperation of thrombocytopenia was 24 and 35 days in each cycle. ConclusionsThe FLAG-IDA induction regimen for the treatment of high-risk leukaemia patients is an established protocol, with good tolerance and acceptable toxicity levels that offers an opportunity for facilitating the transplantation of haematopoietic progenitors.

Photodynamic therapy for unresectable cholangiocarcinoma: contribution of single operator cholangioscopy for targeted treatment

Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis and survival. Single operator cholangioscopy (SOC) has been used for targeted laser illumination. We analyzed our growing experience of SOC with direct PDT. This is a retrospective analysis of a consecutive series of patients prospectively entered into a registry. Forty-five patients (24 male, aged 67.3 ± 10.6 years) were treated with PDT for cholangiocarcinoma during a five-year period. Thirty-two patients were treated with ERCP and PDT alone, and 13 were treated with ERCP and PDT using SOC. The two groups were then compared to observe any statistically significant difference in regards to age, gender, serum bilirubin, MELD score, adverse effects, or survival. An overall median of 1 PDT session per patient (range: 1-9) was performed. Twenty-six total sessions of PDT using SOC were performed in 13 patients with a median of 2.0 sessions per patient (range: 1-6). Median global survival was 168 days (range: 26-1353). Median survival for the PDT-only group was 200 days, and median survival for the PDT-with-SOC group was 386 days (p = 0.45). There was a statistically significant difference (p < 0.0001) between the two groups in regards to fluoroscopy time, with the PDT-only group having a median time of 21.1 min and the PDT-with-SOC group having a median time of 11.1 min. PDT related complications included 7 cases of mild phototoxicity and one case of moderate phototoxicity requiring hospitalization. SOC permits targeted therapy during PDT and can be successfully performed without adverse events while simultaneously reducing exposure to radiation.

Impact of preoperative levels of hemoglobin and albumin on the survival of pancreatic carcinoma

Pancreatic cancer presents the worst survival rates of all neoplasms. Surgical resection is the only potentially curative treatment, but is associated with high complication rates and outcome is bad even in those resected cases. Therefore, candidates amenable for resection must be carefully selected. Identification of prognostic factors preoperatively may help to improve the treatment of these patients, focusing on individually management based on the expected response. We perform a retrospective study of 59 patients with histological diagnosis of pancreatic carcinoma between 1999 and 2003, looking for possible prognostic factors. We analyze 59 patients, 32 males and 27 females with a mean age of 63.8 years. All the patients were operated, performing palliative surgery in 32% and tumoral resection in 68%, including pancreaticoduodenectomies in 51% and distal pancreatectomy in 17%. Median global survival was 14 months (Range 1-110).We observed that preoperative levels of hemoglobin under 12 g/dl (p = 0.0006) and serum albumina under 2.8 g/dl (p = 0.021) are associated with worse survival. Preoperative levels of hemoglobin and serum albumina may be prognostic indicators in pancreatic cancer.

Single-lung transplantation in patients with previous contralateral pneumonectomy: technical aspects and results

Single-lung transplantation (SLTX) in patients with previous contralateral pneumonectomy (PN) is a rarely observed situation. Intrathoracic anatomical changes caused by mediastinal shift may complicate the surgical procedure. We collected observations from different transplantation centres to analyse the technical aspects and results. Between July 1990 and September 2008, 14 patients (seven women and seven men) with previous PN underwent SLTX for end-stage pulmonary failure. Patients were categorised in three groups according to lung disease: cystic fibrosis bronchiectasis (group 1; n=4), non-cystic fibrosis bronchiectasis (group 2; n=6) and bronchioloalveolar carcinoma (group 3; n=4). We reviewed patients' characteristics according to mediastinal shift, thoracic approach, bypass cannula procedure, perioperative difficulties and immediate and long-term results. Median age was 19.5, 33.5 and 52.5 years in groups 1, 2 and 3, respectively; there were nine left and five right cases of SLTX. Surgery was performed by sternotomy (n=4), anterolateral thoracotomy (n=4), clamshell (n=4) or posterolateral thoracotomy (n=2). Cannulas for bypass were inserted into femoral (n=7) or central vessels (n=5) or both (n=2). Mediastinal shift did not complicate surgical procedure but rendered cannulation more difficult with ensuing cardiopulmonary bypass dysfunction (n=3) and early bronchial complications (n=2). In-hospital mortality rate was 29% (4 out of 14 patients), including two deaths due to perioperative difficulties linked to mediastinal shift. Median global survival was 108 months. Median survival was higher in group 2 (108 months vs 1 month in the other groups) and in case of PN during childhood (n=6, median survival 108 months corresponding to one death). SLTX after PN is associated with high perioperative morbidity and mortality due to mediastinal shift. Best results are observed in patients undergoing PN for non-cystic fibrosis bronchiectasis and during childhood. Anatomical changes induced by PN must be anticipated to adapt the thoracic approach and cardiopulmonary bypass access.

Efficacy of Lenalidomide in Different Clinical Settings in Patients with Relapsed or Progressive Multiple Myeloma: Updated Analysis of 111 Cases of the Spanish Compassionate Use Program

Aim: To evaluate the efficacy of Lenalidomide (Len) as compassionate use in relapsed or progressive Multiple Myeloma (MM) up to its approval in Spain.Patients and Methods: GEM-PETHEMA designed a transverse and retrospective, multicenter analysis of MM cases which Len compassionate use was requested until December, 2007. The decision to treat these patients was previous and independent from the decision to conduct the present analysis and depended only on the clinical criteria of the responsible doctors. At least, one response assessment was a must for efficacy analysis.Results: 111 MM patients have been included. Eligible patients for efficacy were 103. Mean age was 65.7 (38–85); 53 m, 50 f. Previous median lines of therapy were 3 (1–8): 92 (89.3%) have received bortezomib; 37 (35.9%) autologous PBSCT and 26 (25.2%) thalidomide. Extramedullary plasmocitomas were present in 25 (24.3%). Mean Len dose was 22.8 mg (± 4.9): 82 (79.6%) received the standard dose and schedule (25 mg d for 3 w every 4 w) and 21 (20.4%) received less dose and/or different schedule. 92 (89.3%) received Dexametasone (mean dose 58.33 mg/w) [± 35.8]). Response: 4 (3.9%) sCR, 11 CR (10.7%), 12 VGPR (11.7%), 41 PR (39.8%), 20 SD (19.4%), 13 PD (12.6%), 2 NE (1.9). Among groups, response equal or superior to PR was observed in all settings: 64.1% in prior exposed to bortezomib, 46.1% in prior exposed to thalidomide and 40.0% in patients with extramedullary plasmocitomas. Previous transplant, the number of previous lines received, renal failure, age, or cytogenetic did not affect significantly the overall response rate. Median duration of treatment was 7.7 m (1–21); median TTP was 8.3 m and median global survival since starting Len therapy was 11 m (6–22). Median survival since diagnostic was 49 m (40–60). At the time of analysis, 46 (45.5%) patients were still on Len therapy, and 72 (79.6%) were alive. Toxicity: ≥ grade II: neutropenia, 51 (46.4%); thrombocytopenia, 39 (35.5%); DVT, 5 (4.5%); rash, 3 (2.7%); neutropenic fever, 8 (7.3%); others, 13 (11.8%). DVT/PE prophylaxis was used in 89 (86.4%) patients: LWMH in 43.8 % and low dose aspirin in 48.3 %. No PE was reported.Conclusions: Lenalidomide is effective in this heavily pre-treated MM population-progressive or refractory to standard therapy-even in different clinical settings. The most frequent association to Len was intermediate dose of Dex. Although response rate was superior in patients exposed previously to bortezomib, no differences on duration and survival were observed. Patients with extramedullary plasmocitomas showed also response. Toxicity, mainly myelosupression was predictable and manageable with dose adjustments and cytokine support.

Primary Invasive versus Progressive Invasive Transitional Cell Bladder Cancer: Multicentric Study of Overall Survival Rate

Introduction and Objective: When feasible, the treatment for all-invasive bladder cancer is radical cystectomy. The aim of the present study was to analyze the prognostic difference, disease-specific survival rate, of muscle-invasive transitional cell cancer of the bladder (TCCB) for progressive invasive TCCB. Patients and Methods: A retrospective multicentric analysis was performed studying a total of 242 patients who underwent radical cystectomy for invasive TCCB from 1993 to 2005. The patients were divided into two groups: group 1 included 57 patients with progressive invasive TCCB, and group 2 included 185 patients with primary invasive TCCB. Both groups were further divided according to the pathological findings in pT2/3 (muscle and/or perivesical fat invasion), pT4 (adjacent organs/structure invasion), N+ (positive lymphatic nodes) and M+ (distant organ metastasis). Several tests were employed for statistical analysis: χ², Mann-Whitney, Kaplan-Meier method and Wilcoxon (Breslow) method were used to compare the possible survival curve differences of groups 1 and 2. Multivariated analysis determined by proportional risk regression excluded sex, age and disease stage interferences in the final results. Results: The average time for a superficial TCCB to become muscle-invasive was 37.4 months, and the average number of transurethral resections performed in each patient was 3. The average and median global survival rates were, respectively, 96 and 88 months in group 1 and 98 and 90 months in group 2, without a statistically significant difference (p = 0.0734). The 1-year survival rate was 84.32% in group 1 and 76.54% in group 2. After 3 years of follow-up the survival rate fell to 74.50% in group 1 and to 59.05% in group 2. Finally, the 5-year survival rate was 57.94% in group 1 and 52.24% in group 2. Conclusion: In the present study, patients with primary invasive and progressive invasive TCCB showed a similar 5-year disease-specific survival rate. Pathological stage (pTN, N and M) and patient demography did not interfere with the results.

Non small cell lung cancer – Comparison between clinical and pathological staging

Lung cancer (LC) staging remains a clinical challenge as it determines the disease's prognosis and treatment. Surgery is the best option for controlling non-small cell lung cancer (NSCLC) and the only potential cure. In this setting, lung cancer staging helps select patients who will benefit from surgery, excluding inoperable patients and including patients with resectable lesions. The aim of this study is to compare clinical staging (TNMc) with pathological staging (TNMp) and to evaluate diagnosis, complementary treatment and survival of these patients.This is a retrospective study that included patients with non-small cell lung cancer or with highly sus- picious lesions who had undergone surgery and were followed up in the Hospital de São João lung cancer unit between January 1999 and December 2003. It is based on clinical files and pathology reports.73.3% of this group of 60 patients were male, with median age 59.2 years. The most frequent TNMc stages were 41.7% T1N0M0 and 36.7% T2N0M0. Thoracotomy for therapeutic purpose was performed in 80% and thoracotomy for diagnostic purpose also in the remaining 20%. In 6.7% the resection was incomplete. The most frequent TNMp stages were T2N0p in 33.3%, T2N1p in 15.0% and T2N2p in 13.3%. There was a significant difference between the two staging types, with upstaging in 65.0%, down staging in 67% and only 28.3% keeping the same stage. The most frequent differences were from T1N0c to T2N0p and from T2N0c to T2N1p. The global agreement between both staging methods was 21.7%. Median global survival was 43 months.In conclusion, while clinical staging was less accurate, it did not determine important changes in therapeutic strategy and survival. For the future, we should consider using other diagnostic tools and other biological factors to complement the anatomical information that we currently use.

Cancro do pulmão de não pequenas células – Comparação entre o estadiamento clínico e o patológico

Lung cancer (LC) staging remains a clinical challenge as it determines the disease’s prognosis and treatment. Surgery is the best option for controlling non-small cell lung cancer (NSCLC) and the only potential cure. In this setting, lung cancer staging helps select patients who will benefit from surgery, excluding inoperable patients and including patients with resectable lesions. The aim of this study is to compare clinical staging (TNMc) with pathological staging (TNMp) and to evaluate diagnosis, complementary treatment and survival of these patients.This is a retrospective study that included patients with non-small cell lung cancer or with highly suspicious lesions who had undergone surgery and were followed up in the Hospital de São João lung cancer unit between January 1999 and December 2003. It is based on clinical files and pathology reports.73.3% of this group of 60 patients were male, with median age 59.2years. The most frequent TNMc stages were 41.7% T1N0M0 and 36.7% T2N0M0. Thoracotomy for therapeutic purpose was performed in 80% and thoracotomy for diagnostic purpose also in the remaining 20%. In 6.7% the resection was incomplete. The most frequent TNMp stages were T2N0p in 33.3%, T2N1p in 15.0% and T2N2p in 13.3%. There was a significant difference between the two staging types, with upstaging in 65.0%, down staging in 67% and only 28.3% keeping the same stage. The most frequent differences were from T1N0c to T2N0p and from T2N0c to T2N1p. The global agreement between both staging methods was 21.7%. Median global survival was 43 months.In conclusion, while clinical staging was less accurate, it did not determine important changes in therapeutic strategy and survival. For the future, we should consider using other diagnostic tools and other biological factors to complement the anatomical information that we currently use.Rev Port Pneumol 2006; XII (4): 337-357

Pancreatic metastases: a multicentric study of 22 patients

To evaluate the diagnosis, treatment and outcome of patients with pancreatic metastases. We retrospectively reviewed the records of patients with pancreatic metastasis managed in the Paris area between 1990 and 2000. The series analyzed included 22 patients, 10 men and 12 women, mean age 61 years (range: 35-76). The primary tumors were renal-cell carcinoma (N=10), colorectal cancer (N=4), lung cancer (N=4), breast cancer (N=2), cutaneous melanoma (N=1) and ileal carcinoid (N=1). The mean interval between primary treatment and presentation was 73.5 months (range: 2-151). Diagnosis was established because of clinical symptoms (N=15) or during surveillance (N=7). Computed tomography (N=19) and endoscopic ultrasound (EUS) (N=18) mainly showed solitary and hypodense/or hypoechoic masses. Histological diagnosis was obtained before surgery by EUS-guided fine needle aspiration (N=6), ultrasound-guided biopsy (N=3) or duodenoscopy (N=3). Among 10 patients with primary renal-cell carcinoma, 7 were treated by surgery. Median global survival was 33 months. Median survival was 61 months in the event of surgical treatment and 20 months in the other patients (ns). Mean survival depended on the type of primary tumor, 61 months for renal-cell carcinoma and 33 for colorectal cancer (P=0.06). Most pancreatic metastases develop from renal-cell carcinoma and can occur several years after nephrectomy. Histological diagnosis is often obtained before surgery. Surgical resection must be discussed as it can allow long-term survival.