Term Survival Of Patients Research Articles

A retrospective analysis of long term outcomes in patients undergoing hepatic resection for large (>5 cm) hepatocellular carcinoma

AimThe treatment of large (>5 cm) hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to report short and long term outcomes and analyze the factors associated with long term survival for patients who underwent hepatic resection for large HCC. MethodsAll patients who underwent hepatic resection for large HCC at the department of Hepato-Pancreato-Biliary Surgery of the First Affiliated Hospital of Anhui Medical University between August 2005 and December 2011 were identified and included for analysis. Demographic and operative data, pathological findings and post-operative outcomes were entered into a computer database. Prognostic factors were analyzed by univariate and multivariate analysis. ResultsNinety-nine patients were included for analysis. Two patients died within 30 days of surgery secondary to hepatic failure. The 1-, 3-, 5-year disease-free survival and overall survival rates following hepatic resection were 67%, 49%, 37% and 77%, 56%, 43%, respectively. Poor histological grade was the only independent predictor of a reduced 5-year disease-free survival. Spontaneous tumor rupture and tumor recurrence were independent predictors of a reduced 5-year overall survival. ConclusionsFor selected patients with large HCC, hepatic resection can be performed safely and effectively with moderate expectation of long term survival. True cure however remains rare.

Abstract B06: Characterizing the effects of hypoxia and hydrostatic pressure on the expression of immunotherapeutic targets in prostate cancer cell lines and donor immune cells in culture

Abstract Introduction: Cancer immunotherapy has changed the paradigm of cancer treatment by harnessing the immune system to identify and eradicate tumors leading to significant improvements in the objective response and long term survival of patients. However, more than 50% of patients do not respond to the most advanced immunotherapeutics in clinical trials, suggesting that further research is needed to understand the mechanism of action and resistance to immune-modulating agents in patients. The current hypothesis is that the tumor microenvironment can modulate the reprogramming of stromal cells caused by chronic inflammation, leading to a suppressed immune system that is highlighted by T-cell exhaustion and anergy. Hypoxia and high interstitial fluid pressure within tumors are elements that may contribute to gene and protein expression changes in stromal, immune and tumor cells in the microenvironment to inhibit immune function and promote cancer proliferation and metastasis. Methods: We have developed a novel primary cell culture bioreactor to modulate both oxygen level (0.1% to 19%) and hydrostatic pressure levels (26 to 260 mmHg / 0.5 psig to 5 psig) to study the effects on gene and protein expression profiles of prostate cancer cell lines and peripheral blood mononuclear cells (PBMCs) derived from donors. We performed high-resolution immunofluorescence imaging and western blot protein expression analysis of primary immuno-therapy targets CTLA-4, PD-1, and PD-L1. In addition, whole transcriptome sequencing was performed on cells across a range of physiologically-relevant culturing conditions to mimic various tumor microenvironments found within the body. Conclusions: We report that prostate cancer cell lines and PBMCs differentially express immunotherapeutic targets when cultured at physiologically relevant tumor microenvironment conditions, resulting in reduced expression of key targets. Analysis of mRNA-seq data revealed alterations in gene expression profiles of immunotherapeutic and drug-target pathways involving CTLA-4 and AR signaling. In contrast, we observed increased CD47 and CD44 expression at low oxygen and high pressure culturing conditions in cancer cell lines and PBMCs. These data highlight the importance of using physiologically relevant microenvironment conditions that include hypoxia and pressure to identify biomarkers and drug target candidates. Citation Format: Bruce A. Adams, James Lim, Tianna Chow, Susan Bernstein, Charles J. Ryan. Characterizing the effects of hypoxia and hydrostatic pressure on the expression of immunotherapeutic targets in prostate cancer cell lines and donor immune cells in culture. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B06.

The Influence of the Distal Resection Margin Length on Local Recurrence and long- term Survival in Patients with Rectal Cancer after Chemoradiotherapy and Sphincter- Preserving Rectal Resection.

BackgroundLow recurrence rates and long term survival are the main therapeutic goals of rectal cancer surgery. Complete, margin- negative resection confers the greatest chance for a cure. The aim of our study was to determine whether the length of the distal resection margin was associated with local recurrence rate and long- term survival.Patients and methodsOne hundred and nine patients, who underwent sphincter-preserving resection for locally advanced rectal cancer after preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral centres were included in the study. Distal resection margin lengths were measured on formalin-fixed, pinned specimens. Characteristics of patients with distal resection margin < 8 mm (Group I, n = 27), 8–20 mm (Group II, n = 31) and > 20 mm (Group III, n = 51) were retrospectively analysed and compared. Median (range) follow-up time in Group I was 89 (51–111), in Group II 83 (57–111) and in Group III 80 (45–116) months (p = 0.326), respectively.ResultsUnivariate survival analysis showed that distal resection margin length was not statistically significantly associated with overall survival or local recurrence rate (p > 0.05). In a multiple Cox regression analysis, after adjusting for pathologic T and N stage (yT, yN), distal resection margin length was still not statistically significantly associated with overall survival.ConclusionsOur study shows that close distal resection margins can be accepted as oncologically safe for sphincter-preserving rectal resections after preoperative chemoradiotherapy.

Prognostic factors for long term survival in patients with advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally, large cell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors such as weight loss, radio lung and doublet platinum-based. On the other hand, it excludes significant factors such as gender, age and smoking.

Potentially curative multivisceral resections for locally advanced colorectal cancer

Background. Performing multivisceral resections in locally advanced colorectal cancer is the only way to achieve the surgical radicality in the treatment of this disease. The frequency of such cases remains high as a result of the global increase in morbidity and poor health culture of the population. Locally advanced colorectal cancer has exclusive specificity in terms of its location - upper abdominal floor, pelvic area and requires multidisciplinary surgical skills and experience. In this publication are reported early perioperative results in 128 cases of potentially curative multivisceral resections. Aim. To assess the early perioperative results in patients with multivisceral resections for advanced colorectal cancer. Material and method. For period of 8 years 2007 – 2014, 191 patients with advanced colorectal cancer were operated. In 128 cases multivisceral resections were performed in attempt for achieve surgical radicalism. Results. Average age in the group was 66.7years. Perioperative mortality amounted to 3.1%(4 patients). Perioperative complications were observed in 25 (19.5%) patients. Conclusion. Surgery is the only method for achieve long term survival in patients with advanced colorectal cancer. Performance of multivisceral resections is challenging for the surgeon and often multidisciplinary approach is needed. Key words. Multivisceral, locally advanced, colorectal

Long term survival in patients surgically treated for gallbladder cancer

Long term survival in patients surgically treated for gallbladder cancer

284 Long Term Survival of patients undergoing TIPS in Budd-Chiari Syndrome

284 Long Term Survival of patients undergoing TIPS in Budd-Chiari Syndrome

Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer

There is some uncertainty about pathological grading of mucinous colorectal adenocarcinoma, defined as colorectal cancer demonstrating at least 50% mucinous differentiation. Under the WHO 2000 classification mucinous colorectal cancer was considered high grade. However under the current WHO 2010 classification microsatellite unstable/mismatch repair-deficient (MSI/MMRd) mucinous colorectal cancer is considered low grade, whereas microsatellite stable/mismatch repair proficient (MSS/MMRp) tumours are high grade. However there is little empirical evidence for this approach. We therefore compared the long term survival of patients with MSI/MMRd vs MSS/MMRp mucinous colorectal cancer in a large unselected cohort of patients undergoing surgery at our institution from 1998 to 2011. There were 2608 patients in the cohort, of which 264 (10.1%) were mucinous. 95 (36%) of the mucinous tumours were microsatellite unstable. The all-cause 5-year survival of mucinous MSI/MMRd colorectal cancer was similar to that of non-mucinous low-grade colorectal cancer (73 vs 67%, P=0.368), and significantly better than that of both non-mucinous high-grade (73 vs 53%, P<0.001) and mucinous MSS/MMRp colorectal cancer (73 vs 57%, P=0.023). The 5-year survival of mucinous MSS/MMRp colorectal cancer was slightly better than that of non-mucinous high-grade patients (57 vs 53%, P=0.027), but significantly worse than that of non-mucinous low-grade colorectal cancer (57 vs 67%, P=0.018). In multivariate Cox regression analysis, conventional histological grade based on glandular differentiation maintained prognostic significance (P=0.003) whereas MSI/MMRd status just failed to be statistically significant (P=0.062). Our findings support the WHO 2010 approach that as a group mucinous MSS/MMRp colorectal cancers are biologically aggressive. However, grading based exclusively on MSI/MMR status may be overly simplistic as conventional grading based on the degree of glandular differentiation still holds greater prognostic significance in multivariate analysis.

Neoadjuvant and adjuvant, floxuridine, leucovorin, oxaliplatin, and docetaxel (FLOD) in patients with locally advanced operable gastroesophageal adenocarcinoma: A phase II study with pathologic responses and long term follow-up.

124 Background: A complete pathological response to neoadjuvant chemotherapy without the use of radiation has infrequently been reported in operable chemo-naïve stage III gastro esophageal adenocarcinoma patients. Methods: Twenty-nine patients were enrolled in this study. Neoadjuvant therapy consisted of Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel and was administered in 2, four week cycles. Chemotherapy consisted on day one and day fifteen; Oxaliplatin, Docetaxel, FUDR, and Leucovorin. The latter two drugs were given concurrently over twenty four hours. On day eight, chemotherapy consisted of Docetaxel, FUDR, and Leucovorin. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathological response were not offered any further therapy. Results: Twenty-four out of twenty-nine patients completed neoadjuvant therapy and underwent esophagectomy. Two were declared inoperable after treatment. Three patients died prior to surgery. The median follow-up of all patients is now sixty months. The median overall survival has not been reached at sixty months. Five yr actual OS is 51%. Clinical response to neoadjuvant therapy was seen in (72.4%) patients. Complete pathological response to neoadjuvant therapy was seen in (16.7%) who are disease free at sixty month follow-ups. Seven out of twenty-four patients achieved partial pathological response (29.1%) and received adjuvant chemotherapy. They are all alive (100%). Eight patients achieved less than partial pathological response and received adjuvant chemotherapy, four out of eight are alive at sixty months (50%). Grade three and four toxicities were seen in sixteen out of twenty nine patients during neoadjuvant therapy. Grade three and four toxicities were seen in six out of fourteen patients during adjuvant therapy. Conclusions: Our chemotherapy regimen of Floxuridine, Leucovorin, Oxaliplatin and Docetaxel (FLOD) has resulted in long term survival in patients with adenocarcinoma of the esophagus. Clinical trial information: NCT00448760.

Mechanical chest compressions in the coronary catheterization laboratory to facilitate coronary intervention and survival in patients requiring prolonged resuscitation efforts.

BackgroundResuscitation after cardiac arrest (CA) in the catheterization laboratory (cath-lab) using mechanical chest compressions (CC) during simultaneous percutaneous coronary intervention (PCI) is a strong recommendation in the 2015 European Resuscitation Council (ERC) guidelines. This study aimed at re-evaluating survival to hospital discharge and assess long term outcome in this patient population.MethodsPatients presenting at the cath lab with spontaneous circulation, suffering CA and requiring prolonged mechanical CC during cath lab procedures between 2009 and 2013 were included. Circumstances leading to CA, resuscitation parameters and outcomes were evaluated within this cohort. For comparison, patients needing prolonged manual CC in the cath lab in the pre-mechanical CC era were evaluated. Six-month and one year survival with a mechanical CC treatment strategy from 2004 to 2013 was also evaluated.ResultsThirty-two patients were included between 2009 and 2013 (24 ST-elevation myocardial infarction (STEMI), 4 non-STEMI, 2 planned PCI, 1 angiogram and 1 intra-aortic counter pulsation balloon pump insertion). Twenty were in cardiogenic shock prior to inclusion. Twenty-five were successfully treated with PCI. Median mechanical CC duration for the total cohort (n = 32) was 34 min (range 5–90), for the 15 patients with circulation discharged from the cath-lab, 15 min (range 5–90), and for the eight discharged alive from hospital, 10 min (range 5–52). Twenty-five percent survived with good neurological outcome at hospital discharge. Ten patients treated with manual CC were included with one survivor.DiscussionEighty-seven percent of the patients included in the mechanical CC cohort had their coronary or cardiac intervention performed during mechanical CC with an 80 % success rate. This shows that the use of mechanical CC during an intervention does not seem to impair the interventional result substantially. The survival rate after one year was 87 %.ConclusionsAmong patients suffering CA treated with mechanical CC in the cath-lab, 25 % had a good neurological outcome at hospital discharge compared to 10 % treated with manual CC. Long term survival in patients discharged from hospital is good.

Prednisolone in alcoholic liver disorder

Aim and Objective: Alcohol is leading cause for liver disease and is associated with morbidity and mortality. Several factors including the amount and duration of alcohol consumption affect the development and progression of alcoholic disorder. Alcoholic hepatitis is a devastating acute form of alcoholic liver disease (ADL). Prednisone for alcoholic liver disease is an effective medication and it improves short term survival in patients. Background: Alcoholic hepatitis is a clinical syndrome characterised by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol consumption. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. Result: Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. Prednisolone Reduced mortality, improved risk-benefit. Treatment with Prednisolone improves the short term survival of patients with severe biopsy proved alcoholic hepatitis.

Survival Benefit of Intravenous Busulfan (120 mg/M2) and Fludarabine Myeloablative Regimen for Treatment of Myeloid Malignancies

Background: Intravenous fludarabine and busulfan 130 mg/m2 (Flu/Bu) conditioning regimen has induced the long term survival with a low treatment related mortality rate. However, there have been few reports on long term survival of patients undergoing allo-HSCT with intravenous Flu/Bu regimen. Therefore, we conducted a retrospective study of 42 patients diagnosed with myeloid malignancies received allo-HSCT with intravenous fludarabine and busulfan (120 mg/m2) regimen between 2006 and 2015 at Ramathibodi hospital. The aim of our study was to observe the long term survival and the complication after transplantation. Findings: Thirty- four, three and five patients were AML, MDS and CML-CP respectively. With a median followup of 95 months, 1- year EFS and 8- year EFS were 82 and 70% respectively. Overall survival (OS) rate at 1 and 8 years were equally observed in 88%. Patient younger than age 45 years had significantly longer OS than patients aged 45 years and older (96 vs 70%, p=0.019). Eight- year OS in AML, MDS and CML were 88, 67 and 100% respectively. Acute and chronic graft versus host disease were found in 29 and 46.3% of 41 evaluable patients respectively. Whereas the rates of sinusoidal obstruction syndrome, sepsis, CMV reactivation, cyclosporine and tacrolimus induced thrombotic microangiopathy were 2, 10, 12, 5 and 2% respectively. Non- relapse mortality rate at day +100, 1 and 8 year were only 9.5, 13.8 and 13.8% respectively. There was no neurological toxicity, severe mucositis, secondary malignancy or therapy related MDS syndrome in this study. Conclusion: Allogeneic hematopoietic stem cell transplantation with intravenous fludarabine and busulfan at the dose of 120 mg/m2 was well tolerated and demonstrated impressive treatment outcomes in young adult patients diagnosed with myeloid malignancies.

An Operational Definition of Primary Refractory Acute Myeloid Leukaemia Which Allows Early Identification of Patients for Whom Allogeneic Stem Cell Transplantation Represents the Only Curative Therapy

PurposeResistance to induction chemotherapy (IC) is an important adverse prognostic factor in adults with newly diagnosed acute myeloid leukaemia (AML), particularly older patients. Despite its therapeutic relevance there is however no universally agreed definition of primary refractory AML (PREF AML). Nor has the role of allogeneic stem cell transplantation (alloSCT) been defined in this clinical setting in a large patient cohort. To address these issues we examined long term outcomes in patients with refractory AML after IC, identified using three differing criteria.Patients and MethodsResponse to IC was documented in 8907 newly diagnosed patients with AML treated on UK MRC and NCRN trials protocols from 1988-2012. Overall survival and predictors of outcome were studied in patients defined using the following three different possible criteria of resistance to induction chemotherapy: failure to achieve complete marrow remission (CR) after one cycle of IC (REF1A), less than a 50% reduction in blast numbers with >15% residual blasts after one cycle of IC (REF1B) and failure to achieve a CR after two courses of IC (REF2). CR was defined using conventional criteria of <5% myeloblasts 14 days following IC in a non-hypocellular bone marrow. 431 patients identified using the three criteria of refractoriness proceeded to an allogeneic SCT.Results2548 patients failed to achieve a CR after one cycle of IC (REF1A) of whom808 patients fulfilled REF1B criteria. 485 patients failed to achieve CR after two courses of IC (REF2). Overall survival (OS) was significantly reduced in patients fulfilling any of the criteria for refractory disease when compared with patients achieving a CR following one cycle of IC. Specifically, 5 yr OS for patients in cohorts REF1A, REF1B and REF2 was 17%, 9% and 8%, respectively, compared with 40% for patients achieving a CR after one course of IC (p <0.0001). REF1B patients who achieved a CR following course 2 had a 5 yr OS of 23%, significantly worse than patients in CR post course 1 (p<.0001) and those in the REF1A group who achieved CR after course 2 (32%, p=.0009).The same risk factors predicted for the presence of refractory disease defined by the three different criteria studied and included cytogenetics, presentation WBC, secondary disease, year of diagnosis, intensity of chemotherapy and age. Factors associated with long term survival in all cohorts included cytogenetics, age, performance status, year of diagnosis, Flt3-Itd status and treatment with alloSCT.Analysis of the impact of transplant on outcome demonstrated that alloSCT was the most effective therapeutic modality to deliver long term survival in all but one subgroup of refractory disease. We analysed each cohort as a whole and by age (<50 yrs and 50+ yrs) in order to reflect changes in transplant practice with the advent of reduced intensity regimens. Mantel-Byar analysis demonstrated that the OS in allografted patients was significantly improved compared with non-transplant patients in the REF1B (HR 0.58 (0.46-0.74), p=0.00001) and REF 2 (HR 0.55 (0.41-0.74), p=0.0001) cohorts and those in the REF1A cohort over 50 years of age (HR 0.75 (0.62-0.91), p =0.003); although there was no difference in REF1A patients under the age of 50 (HR 1.06 (0.87-1.28), p=0.6; test for interaction p=0.01). In a combined group of patients (REF3) who were either REF1B or REF2, transplant significantly improved outcomes in all age groups (HR 0.58 (0.49-0.69), p<0.00001) with Mantel-Byar estimates of survival of 30% vs 6% in patients under 50 years, and 14% vs 2% in those older than 50 years.ConclusionThis is the first study to assess the impact of allogeneic SCT on outcome in patients with PREF AML using differing definitions of refractoriness. Our data clearly demonstrates that alloSCT is the only treatment modality which delivers long term survival in patients with refractory disease defined using REF1B and REF2 criteria and older REF1A patients. This novel analysis of outcome in PREF AML demonstrates that patients who will benefit from alloSCTcan be reliably identified by their age and an early assessment of percentage blast reduction after the first course of IC. Such a diagnostic strategy permits the early identification of patients in whom alloSCT represents the only curative treatment option and presents an opportunity to deliver SCT at the earliest opportunity, avoid further ineffective therapy and potentially improve transplant outcomes. DisclosuresRussell:Therakos: Other: shares.

Life Expectancy in Follicular Lymphoma Is Mainly Determined By Response to First LINE Treatment: A LONG-TERM Survey on 597 Patients

BACKGROUNDFollicular lymphoma (FL) is the most common indolent form of non-Hodgkin's lymphoma. However, FL is a heterogeneous disorder and in a proportion of patients, the disease is very resistant to standard frontline therapies. In the current analysis clinical features and outcome to primary treatment were evaluated in a large series of FL patients who were consecutively treated at the Hematology Centers of Bergamo and Torino, Italy between 1976 and 2012. The aim of the study was to define the rate of refractory disease and the long term survival of patients according to response to their primary treatment.METHODSMedical records of 597 FL patients were reviewed. In front line therapy, rituximab was employed in 330 patients (55%), front-line high dose therapy with autograft (HDS) was administered in 58 patients (9.7%). Primary refractory disease was defined as full refractoriness (stable or progressive disease) or progressive disease within six months after initial response. Univariate analysis was done for prognostic factors including gender, age at diagnosis (age≤60 and >60 years), histological grade, IPI score (low=0-2 versus high=3-5), bone marrow (BM) involvement, rituximab administration in 1st line treatment, lymphocyte to monocyte ratio at diagnosis (>2.6 vs ≤2.6), presence of primary refractory disease, and the administration of front-line HDS. Cox model was also used for multivariate analysis.RESULTS: A total of 375 patients (63%) were older than 60 years (range: 18-88) and 49% were males. There were 476 patients (79.7%) with stage III-IV, 286 patients (48%) with BM involvement, 185 (31%) had a high IPI score and 28 patients (5%) presented with high histological grade. Eighty-seven patients (13%) displayed primary refractory disease. At a median follow-up of 8 years, median overall survival (OS) was 25 years for all patients, 32.6 years for responsive patients compared to 5 years for primary refractory patients (p=<0.0001). Among primary refractory patients, those with fully refractory disease had a shorter survival (median OS: 2.7 years) compared to patients with early progressive disease (median OS: 5 years). The strikingly different outcome of primary refractory vs. responsive patients is shown in the Figure 1. A significant prolonged survival was observed in patients who were treated with rituximab in primary therapy. The median OS is not reached for rituximab treated patients compared to 19 years for those who did not receive rituximab. Median OS was 25 years for patients with low IPI and 14.6 years for the high risk group. By univariate analysis, age and BM involvement were also significant prognostic factors for OS. Median OS for patients 60 years old or younger compared to older patients were 32.6 versus 13 years, respectively. The median survival was not reached for patients without BM involvement vs 19 years for patients with BM involvement (p=0.001). By multivariate analysis high IPI, refractory disease and not receiving rituximab in first line regimens were independent negative prognostic factors for OS, as detailed in Table 1.CONCLUSION: FL patients who display responsive disease to their primary treatment have a very long life expectancy with median survival of 32.6 yrs. Similarly to the aggressive lymphoma subtypes, primary refractory disease is of major concern also for FL. Research studies should be focused on the early identification of primary refractory patients to promptly institute adapted therapy for this unfavorable subgroup, and possibly optimize treatment strategies for patients with high-risk FL.Table 1Multivariate analysis for overall survivalParameterHazard Ratio (95% Confidence interval)p-valueAge (yrs): >60 vs. ≤ 601.54 (1.5-2.3).03Histologic grade: 1-2 vs 32.25 (0.5-9.1).3IPI *Score: low (0-2) vs high(3-5)0.59 (0.4-0.9).009Primary Refractory: yes vs no4.40 (3.0-6.5)< .0001Rituximab 1st line: yes vs no0.56 (0.4-0.8).005BM# involvement: yes vs no1.44 (1.0-2.1).06*International prognostic index was used to have a uniform prognostic factors scoring system for patients treatedover the three decades of the survey.#Bone marrow [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract 13813: Intravascular Vagal Nerve Stimulation in Acute Myocardial Infarction Markedly Reduced Infarct Size and Improved Cardiac Function in the Long Term

Backgrounds: In acute myocardial infarction (AMI), the extent of myocardial damage governs the progression to heart failure in the long-term. Therefore, reducing the myocardial damage is prerequisite to prevent chronic heart failure. Although vagal nerve stimulation (VNS) has been repeatedly demonstrated to have the powerful anti-infarct effect, technical difficulties preclude its clinical applications. Recently we developed an new percutaneous, intravascular VNS (iVNS). In this study, we investigated whether iVNS reduces the infarct size and prevents heart failure one month after ischemia reperfusion (IR). Methods: In mongrel dogs, we ligated the left anterior descending coronary artery for 3 hours and reperfused. We transvascularly stimulated the right vagal nerve with a pacing catheter in the superior vena cava. We maximized the intensity of iVNS that did not deteriorate hemodynamics (amplitude; 5.1±2.1 V, pulse width; 0.2ms, frequency; 10 Hz). We started iVNS at the onset of ischemia (iVNS0, n=7) or 90 min after the onset of ischemia (iVNS90, n=7) and continued to 60 min after reperfusion. One month after IR, we compared the infarct size, left ventricular (LV) function and hormonal responses among 3 groups including the no treatment group (IR, n=10). Results: Both iVNS0 and iVNS90 significantly reduced the infarct size (IR: 11.6±3.1, iVNS0: 2.4±2.1, iVNS90: 4.5±1.9%, p&lt;0.05, Figure), improved LV ejection fraction (IR: 50±7, iVNS0: 61±6, iVNS90: 60±5.1%, p&lt;0.05) and decreased LV end-diastolic pressure (IR: 14.6±1.9, iVNS0: 4.2±1.0, iVNS90: 5.0±2.8mmHg, P&lt;0.05). The benefits were larger in iVNS0 than iVNS90. Conclusion: Short term iVNS delivered prior to coronary reperfusion markedly reduced the infarct size and preserved LV function one month after ischemia. Since we can transvascularly deliver iVNS, it may serve as a new non-pharmacological therapeutic strategy and contribute to improve the long term survival in patients with AMI.

Abstract 13210: Concomitant Septal Myectomy Can Improve Left Ventricular and Atrial Function Detected by 2d Speckle Echocardiography as Well as Long term Survival In Patients Undergoing Aortic Valve Replacement With Marked Ventricular Hypertrophy

Introduction: Patients requiring aortic valve replacement (AVR) frequently have left ventricular hypertrophy (LVH) /sigmoid septum, which causes persistent outflow obstruction (LVOTO) postoperatively. Surgical AVR enables such patients to undergo concomitant septal myomectomy. However, the effect on their postoperative myocardial function and long-term outcome is yet to be elucidated. Hypothesis: Concomitant myectomy may be beneficial for selected patients undergoing surgical AVR and possible LVOTO. Methods: Postoperative outcome and myocardial functional changes before and after surgery were assessed by conventional and 2D speckle tracking echocardiography in patients undergoing AVR and myectomy (Group M, n=16, male 21%, mean age 76.0 years) The results were compared with age/sex-matched controls who had marked LVH/LVOTO undergoing AVR alone (Group C, n=27). The relation between preoperative echo-derived local myocardial function and histology of resected myocardium in Group M was also investigated. Results: Preoperative echo parameters were not different between the groups. However, a decrease in LV E/E’ and an increase in the absolute value of basal septum longitudinal strain were seen postoperatively only in Group M (17.3±4.3 to 15.2±2.6, p=0.013, -9.3±4.5 to -12.8±3.8%, p=0.008, respectively). Peak LA strain values increased in both groups, but the improvement was more apparent in Group M (Group M; 20.6±5.3 to 28.3±7.1%, p=0.008, Group C; 21.9±5.9 to 26.9±6.0%, p=0.046,). Survival following surgery was better in Group M than Group C (30 days, 1 and 5 year, 100.0% vs 88.2%, 100.0% vs 75.6%, 100.0% vs 68.8%, respectively, p=0.028). Histology of resected myocardium in Group M showed remarkable fibrosis (mean 6.8%, range 1-17%) and thickness of endocardium (mean 1031μm, range 287-2505μm), and the degree of fibrotic area was significantly correlated with preoperative basal septum strain value (r2=0.6, p=0.041). Conclusions: Concomitant septal myectomy with AVR improves postoperative LV diastolic function, as well as LA function. Furthermore, it improved short and long-term survival as compared to those undergoing AVR alone. AVR with myectomy may be a beneficial option for patients with marked LVH /sigmoid septum-related LVOTO.

Role of [11C] methionine positron emission tomography in the diagnosis and prediction of survival in brain tumours

Objective[11C] methionine (MET) positron-emission tomography (PET) is a useful diagnostic and therapeutic tool in neuro-oncology. The aim of this study was to evaluate the relationship between MET uptake and the histopathological grade in both primary brain tumours and brain metastases. A secondary goal was to assess the relationship between MET uptake and patients’ survival after surgery. MethodsWe reviewed a consecutive series of 43 PET studies performed at our institution. Out of the 43 patients studied, 35 harboured primary brain tumours (3 grade I, 12 grade II, 7 grade III and 13 grade IV) and 8 patients had brain metastases. We measured the tumour/cortex ratio (T/C ratio) on each PET study and we investigated the correlations among the tracer uptake, tumour grade, tumour type, MRI parameters and outcome. ResultsThe mean T/C ratio was 1.8±0.9 for benign lesions and low grade gliomas (grade I and II) and 2.7±1 for high grade gliomas (grade III and IV). In brain metastases it was 2.5±0.7, with a significant difference in MET uptake between low and high grades gliomas (P=0.03). There was no statistically significant difference among all different histologic types.We found that both contrast enhancement and perfusion studies correlate with MET uptake in brain tumours. Moreover, in Kaplan–Meier curves, the T/C ratio adversely affects long term survival in patients with brain tumours (P=0.01). ConclusionsMET PET appears to be useful in diagnosis and evaluation of potential malignancy in brain tumours. MET uptake is also related with the overall survival in patients with brain tumours. Nevertheless, further studies are needed in order to define its possible clinical implications in identifying patients at high risk of tumour progression or resistance to therapy.

Serum lactate as predictor of morbidity, mortality and long term survival in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Introduction: Serum lactate elevation has been used as a marker of tissue hypoxia in the setting of perioperative monitoring and critical care. It has also been correlated with perioperative morbidity and mortality. Cytoreductive surgery (CRS) & hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis is a major abdominal operation, requiring meticulous perioperative care. The aim of this study is to assess the clinical use of lactate measurements after CRS & HIPEC and its prognostic value in terms of immediate postoperative morbidity and mortality, as well as long term survival. Material & Methods: Of 140 patients diagnosed with peritoneal carcinomatosis who underwent cytoreductive surgery and HIPEC were prospectively studied. Serum lactate was measured by air blood gases analyser intraoperatively (just before the administration of HIPEC) and then daily till the fifth postoperative day. Postoperative complications were recorded and divided into two groups according to Clavien Dindo classification. Results: Intraoperative lactate measurements have not been associated with postoperative morbidity and mortality. On the other hand, lactate measurements on postoperative days 3 and 4 are of clinical significance. Specifically, an increase of 1 mmol/L of the average lactate value of days 3 and 4 raises the risk of a minor complication (Grades I to IIIa) by 1.9, the risk of a major complication (Grades IIIb to V) by 10.9 and the risk of mortality by 32.1%. Conclusions: The average of day 3 and 4 postoperative day lactate level is an independent predictor of morbidity and mortality in patients undergoing CRS and HIPEC.

Long-term response with everolimus for metastatic renal cell carcinoma refractory to sunitinib-sorafenib sequence

We presented a 39-year-old male who developed progressive cancer disease 4 years after nephrectomy due to clear cell carcinoma. He was diagnosed with locally reccurence and metastases to the liver, spleen and abdominal muscles. The patient was treated with sunitinib and then after disease progression – with sorafenib. We observed 18 months of cancer control (TKI-TKI). After second progression everolimus was administered. Third line everolimus therapy helped to achieve durable stable disease with PFS 46 months till now (May 2015). The patient remains in very good performance status with minimal toxicity from the regimen. This case illustrates a long term survival for patients with metastatic renal cell carcinoma, a malignancy with historically poor prognosis. The use of three sequential targeted therapies (TKI – TKI – mTORi) helped to achieve over 5 years or disease control, with rarely seen long-term response to third line treatment (mTORi) – where stabilization is good enough. We discussed therapeutic strategies in metastatic renal cell carcinoma according to the literature and therapeutic possibilities in Poland.

Clinical and pathological analysis of acute rejection following orthotopic liver transplantation.

Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants. From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed. In 86 cases (16.7%), of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff I rejections, 48 Banff II and 13 Banff III. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation. Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.