One-year Actuarial Survival Research Articles

Risk factors indicating the need for surgical therapy in patients with pyogenic liver abscesses.

Percutaneous drainage (PD) and antibiotics are the therapy of choice (non-surgical therapy [non-ST]) for pyogenic liver abscesses (PLA), reserving surgical therapy (ST) for PD failure. The aim of this retrospective study was to identify risk factors that indicate the need for ST. We reviewed the medical charts of all of our institution's adult patients with a diagnosis of PLA between January 2000 and November 2020. A series of 296 patients with PLA was divided into two groups according to the therapy used: ST (n = 41 patients) and non-ST (n = 255). A comparison between groups was performed. The overall median age was 68years. Demographics, clinical history, underlying pathology, and laboratory variables were similar in both groups, except for the duration of PLA symptoms < 10days and leukocyte count which were significantly higher in the ST group. The in-hospital mortality rate in the ST group was 12.2% vs. 10.2% in the non-ST group (p = 0.783), with biliary sepsis and tumor-related abscesses as the most frequent causes of death. Hospital stay and PLA recurrence were statistically insignificant between groups. One-year actuarial patient survival was 80.2% in the ST group vs. 84.6% in the non-ST (p = 0.625) group. The presence of underlying biliary disease, intra-abdominal tumor, and duration of symptoms for less than 10days on presentation comprised the risk factors that indicated the need to perform ST. There is little evidence regarding the decision to perform ST, but according to this study, the presence of underlying biliary disease or an intra-abdominal tumor and the duration of PLA symptoms < 10days upon presentation are risk factors that should sway the surgeons to perform ST instead of PD.

Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study.

Germ cell tumors (GCTs) are uncommon neoplasms predominantly arising in midline tissues. The prognostic significance of histopathology in predicting metastatic GCT behavior is poorly understood. Multicenter international cohort study including 29 patients with GCTs metastatic to brain were retrospectively investigated (18 patients from Mayo Clinic and 11 patients from the intracranial germ cell tumor genome analysis consortium in Japan). Clinical characteristics were analyzed using the Chi-square test (two-tailed) for categorical variables and using the log-rank test for survival data. Median age at treatment was 31years (range 14-58). Primary disease sites were testis (71%), mediastinum (18%), and female reproductive organs (11%). Median metastatic interval was 223days (range, 6-6124). Median follow-up was 346days (range, 1-5356), with 16 deaths (57%) occurring after the median overall survival of 455days. Actuarial one-year survival was 51%; 12-of-16 deaths (75%) were attributed to intracranial disease. Appearance of the same GCT subtype at the metastatic site as the primary was high for non-seminomatous GCT (NSGCT, 64-100%), but low for seminoma/dysgerminoma and mature teratoma (MT, 14, 17%, respectively). Gain of a new component was seen in 4 (20%)-3 of which included embryonal carcinoma (EC) at the primary site (75%). Incidence of cases without seminoma/dysgerminoma increased significantly after metastasis (p = 0.02). Metastatic interval was shorter in cases with histological change (199 vs 454days, p = 0.009). Overall survival was associated with MT primary histopathology (p = 0.02). Histological differentiation at the primary GCT site influences metastatic prognosis. Aggressive behavior is associated with NSGCT, while EC frequently demonstrates multi-directional histological differentiation after brain metastasis, and such histological dynamism is associated with shorter metastatic interval. Most metastases occurred within one year of diagnosis, emphasizing the need for close surveillance in newly diagnosed extra-cranial GCT.

Heart Transplantation in Children after a Fontan Procedure: Better than People Think.

Previous studies have reported that children with a prior Fontan procedure have decreased survival after heart transplantation. We examined 273 primary pediatric heart transplants. Since 1988, 33 (12.1%) of 273 children <18 years old undergoing primary heart transplantation had a Fontan procedure 3.7 ± 4.3 years before transplantation. Compared with 240 (87.9%) non-Fontan primary transplants, the Fontan patients were older (8.8 ± 5.2 vs 6.6 ± 5.9 years; P = .023), but were similar in presensitization and pre-transplant clinical status. More Fontan patients had prior operations (100% vs 51.7%; P < .0001) and needed pulmonary artery reconstruction (100% vs 21.7%; P < .0001). Thirteen (39%) had protein-losing enteropathy. Donor ischemic times (213 ± 73 vs 177 ± 57 minutes; P = .0013) and cardiopulmonary bypass times (199 ± 86 vs 125 ± 53 minutes; P < .0001) were greater in the Fontan group, as were durations of ventilator support (4.4 ± 6.0 vs 2.5 ± 4.3 days; P = .035) and hospital stay (18.6 ± 16.1 vs 14.7 ± 13.1 days; P = NS). The Fontan group had one 30-day mortality. One-year actuarial survival (84.8% vs 86.9%, Fontan vs non-Fontan) and 5-year actuarial survival (70.8% vs 70.3%, Fontan vs non-Fontan) were similar, as was rejection incidence at 1 year (2.0 ± 2.0 vs 1.7 ± 1.9 episodes/patient; P = .3972). Five Fontan patients (18.5%) required retransplantation 4.9 ± 3.6 years post-transplant, compared with 22 non-Fontan patients (9.2%) retransplanted 5.2 ± 3.4 years post-transplant. Contrary to prior reports, we did not identify any early or mid-term disadvantage for children undergoing heart transplantation after a previous Fontan procedure, despite more complex transplant operations. We contend that carefully selected children with a failing Fontan circulation can do as well as other children with heart transplantation.

Gefitinib plus interleukin-2 in advanced non-small cell lung cancer patients previously treated with chemotherapy.

The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

Single-Center Experience of Paired Kidney Exchange: Effects On Outcomes With Variable Shipping Distance and Cold Ischemic Time.

Background: National paired kidney exchange programs benefit patients, but there is a paucity of data on the impact of cold ischemic time (CIT) and shipping distance on transplant outcomes. Methods: This is a single-center study examining outcomes of 53 consecutive cases of paired kidney exchange (2011-2014). One-year actuarial survival rates were determined by Kaplan-Meier analyses. Results: Recipients of paired kidney exchanges received grafts either from our center (n=13, 24.5%) or were shipped from an outside hospital (n=40, 74.5%). For shipped kidneys, the average CIT was 12.5 h (±3.9 h), and the average distance shipped was 1045 mi (±465 mi). Kaplan-Meier one-year actuarial graft survival rates were not statistically different between shipped and non-shipped kidneys, 92% vs 90%, p=0.96, Figure 1. The rate of DGF for shipped kidneys was 10% (4/40) vs 0% (0/13) for non-shipped NKR kidneys (p=0.25). Multivariate analyses controlling for donor age, PRA, HLA match did not demonstrate a statistically significant association between DGF and CIT (p=0.11) and distance shipped (p=0.17). However, the one-year actuarial graft survival rates of kidneys with and without DGF were, 50% and 95.0%, respectively (p=0.01), Figure 2. Conclusions: A statistically insignificant, but clinically significant rate of DGF was observed in living donor kidneys received from external programs. This risk of DGF was not related to CIT and shipping distance in a multivariate analysis. Importantly, DGF was found to be associated with diminished 1-year kidney graft survival. Further study is needed to fully determine the impact of distance and CIT on outcomes of transplants in national paired exchange programs.Figure: No Caption available.Figure: No Caption available.

Abstract P5-14-08: Prospective phase II study of concurrent capecitabine and radiation demonstrates futility in triple negative chemo-resistant breast cancer

Abstract Background: Capecitabine is an established radiosensitizer in rectal and other cancers. We conducted a prospective single arm phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine and radiotherapy. Methods: Patients who had inoperable or marginally operable gross disease in the breast and/or lymph node(s) after chemotherapy or gross disease on the chest wall or in the regional lymphatics after mastectomy were eligible. Patients 1-9 received capecitabine 825 mg/m2 BID daily beginning on the first day of radiotherapy. Excess grade 3 toxicity (%) was observed; the protocol was amended and subsequent patients received drug only on radiation treatment days. Radiation dose was at the discretion of the treating physician (50Gy-72 Gy, with no more than 2.5 Gy/fraction). Response was assessed by a single physician using paired radiation planning CTs (pretreatment and on-treatment after 45 Gy). Clinical correlation to all other available imaging was also made. Kaplan-Meier curves were used to estimate overall survival (OS) and local recurrence-free survival (LRFS). Circulating tumor cells (CTCs) in blood were examined in consenting patients. Results: The trial was stopped early after an unplanned interim analysis prompted by slow accrual suggested futility independent of response. From 2009-2012, 32 patients were accrued; 26 completed protocol specific treatment (17 post-mastectomy radiation with gross nodes, 4 pre-op, 5 aggressive palliation) and are included in this analysis. Median follow up was 7.3 months (interquartile range 6.7 – 17.4). Nineteen patients (73%) had a partial or complete response. Fourteen patients (53.9%) experienced at least one grade 3 non-dermatitis toxicity including 7/9 treated with continuous dosing. Four inoperable patients were treated with pre-op radiation therapy and 3 converted to operable. None achieved a pCR or near pCR. One-year actuarial OS was 52%. There was no difference in OS comparing among PMRT vs. preoperative or palliative RT (P = 0.90). One-year actuarial local recurrence free survival among PMRT patients was 38%. Ten patients had triple negative (TN) receptor status. There was no difference in radiation response by receptor status (P = 0.56); however, treatment was deemed subjectively futile (i.e., converted to operable but death secondary to new widespread M1 disease immediately post-op) in 9 of the 10 patients with TN disease versus 6 of the 16 patients with non-TN disease (P = 0.014). Median OS and 1-yr actuarial OS, among non-TN vs. TN patients were not reached vs. 6.1 months and 77% vs. 10% (P &amp;lt; 0.001), respectively. Eight/fifteen patients tested were positive for CTCs. CTCs did not correlate to receptor status, futility of RT or OS. Conclusions: Capecitabine can be safely administered as a daily concurrent chemoradiation regimen with weekend holidays. However, in this small, prospective and selected cohort, concurrent chemoradiation with capecitabine was futile among patients with TN breast cancer. Alternative strategies are urgently needed in TN patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-08.

Conservative approach in the management of isolated penetrating liver trauma

BackgroundDamage to the liver is the most common cause of death after abdominal injury. The most common cause of liver injury is blunt abdominal trauma. In the case of penetrating injury, non-intervention management has not been adequately addressed. Selective non-operative management of stab wounds especially to the liver has been reported. MethodsThis study was carried out from May 2006 to April 2011 at the Main Alexandria University Hospital, Faculty of Medicine, Alexandria, Egypt. This study consisted of 62 liver trauma patients and the following data were collected: demographics, mechanism of injury, pre-hospital care, hemodynamic status, grade of hepatic injury, associated injuries, failure of non-operative (NOP) management, hospital stay in intensive care unit (ICU) or in the ward and death. Patients were eligible for the study if they sustained isolated penetrating right hypochondrial injury. Assessment of hemodynamic stability was based on routine vital signs. Injury severity was determined from CT and classified by means of the Liver Injury Scale. ResultsThis study was carried out for 62 consecutive patients with hepatic trauma in a five year period. Mean age was 33.6years with a range of 16–54years. The isolated penetrating liver injuries included knives, guns (gunshot & shotgun injuries) and other sharp objects. All patients were treated successfully via NOP management except five patients (8%) who failed NOP management. These five patients were hemodynamically unstable and were unresponsive to crystalloid and blood transfusion. The five patients underwent surgery (suturing, packing, and resectional debridement). Two patients (3.2%) died because of high grade liver injury. The overall actuarial one-year survival in NOP management was 96.8%. ConclusionsLow grade penetrating hepatic injuries (G I-III) can be managed non-operatively with excellent results; even G IV penetrating liver injuries with hemodynamically stable patients can be managed safely non-operatively.

Gastrectomy with D2 lymphadenectomy for gastric cancer: Morbidity, mortality and survival

Background: Gastric cancer is the second leading cause of cancer death worldwide. Ninety percent of gastric cancers are adenocarcinomas. Overall, there is a decline in the incidence of gastric cancer in most countries over the past 50 years. Surgical resection is the most effective treatment for curable gastric cancer.Controversy still surrounds the value of extensive lymph node dissection in the curative treatment of gastric carcinoma.The overall 5-year survival rate among patients with resectable gastric cancer ranges from 10% to 30% in the western world. In contrast, Japanese publications report a marked improvement in survival (between 50% and 62%), largely attributed to lymph node resection known as D2 lymphadenectomy. Methods: The study was a prospective follow-up study on 50 consecutive patients with gastric cancer (without distant metastasis) between March 2007 and February 2010 in the Upper Gastrointestinal Surgery Unit, Faculty of Medicine, Alexandria University, Egypt. Patients less than 65 years with histologically proven and potentially curable gastric cancer were eligible for the study. Preoperatively, all patients underwent upper gastrointestinal endoscopy with biopsies and histopathologic examination. Computed tomography (CT) scans were done to look for metastases. Results: Fifty patients (36 men, 14 women) underwent gastric resection with D2- lymphadenectomy for gastric adenocarcinoma in a three-year period. Mean age was 46.6 years with a range of23-65 years. Almost 44% of patients had preoperative co-morbid disease. Weight loss with epigastric pain and dyspepsia was the most common presenting symptom (80%). Fifty patients underwent D2 resection, fifteen patients with radical total gastrectomy and intra­ abdominal oesophagojejunostomy, and thirty five patients with a subtotal distal gastrectomy and gastrojejunostomy. The hospital mortality rate was 4% (2/50). Morbidity rate was 44% (22/50), some of them presented with more than one complication. The median time of hospital stay was 22 days (mean 22.3, range 13-40). Follow-up included clinical, laboratory and CT examinations of all patients after surgery. In addition, when relapse was suspected, endoscopy with biopsy, and CT scan were performed. During the first 2 years follow-up, locoregional relapses were observed in 2 patients (local lymph nodes relapse). One patient presented with peritoneal recurrence, and 2 patients showed distant spread. The overall actuarial one-year survival in D2 patients was 92% and 76% at two years. Conclusion: The results obtained in our series of patients submitted to gastrectomy with D2 lymphadenectomy suggest that this technique offers low morbidity, mortality and acceptable 2-year survival rates. The survival benefit with D2 is obtained when a tumor invades muscularis propria or penetrates serosa without invasion of adjacent structures.

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients

Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson's index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.

Robotic image-guided reirradiation of lateral pelvic recurrences: preliminary results

BackgroundThe first-line treatment of a pelvic recurrence in a previously irradiated area is surgery. Unfortunately, few patients are deemed operable, often due to the location of the recurrence, usually too close to the iliac vessels, or the associated surgical morbidity. The objective of this study is to test the viability of robotic image-guided radiotherapy as an alternative treatment in inoperable cases.MethodsSixteen patients previously treated with radiotherapy were reirradiated with CyberKnife® for lateral pelvic lesions. Recurrences of primary rectal cancer (4 patients), anal canal (6), uterine cervix cancer (4), endometrial cancer (1), and bladder carcinoma (1) were treated. The median dose of the previous treatment was 45 Gy (EqD2 range: 20 to 96 Gy). A total dose of 36 Gy in six fractions was delivered with the CyberKnife over three weeks. The responses were evaluated according to RECIST criteria.ResultsMedian follow-up was 10.6 months (1.9 to 20.5 months). The actuarial local control rate was 51.4% at one year. Median disease-free survival was 8.3 months after CyberKnife treatment. The actuarial one-year survival rate was 46%. Acute tolerance was limited to digestive grade 1 and 2 toxicities.ConclusionsRobotic stereotactic radiotherapy can offer a short and well-tolerated treatment for lateral pelvic recurrences in previously irradiated areas in patients otherwise not treatable. Efficacy and toxicity need to be evaluated over the long term, but initial results are encouraging.

Successful use of a pneumatic biventricular assist device as a bridge to transplantation in cardiogenic shock

Mechanical circulatory support is a highly effective technology to maintain organ perfusion in patients with cardiogenic shock as a bridge to transplantation. Although implantation of a left ventricular assist device alone is often the preferred configuration, patients with biventricular failure and significant end-organ dysfunction often require biventricular assistance. Between January 2000 and September 2008, 80 patients with severe biventricular failure were accepted for heart transplantation and received a pneumatic biventricular assist devices as a bridge to transplant. Patients were retrospectively divided into 2 groups: those successfully bridged to transplant (Group A) and those who died (Group B). Patients were also divided into 2 periods of implantation: Group X (2000-2005) and Group Y (2006-2008, which used a multidiscipline selection process). Overall success rate to transplantation was 71.3%, with Group Y demonstrating an 82% success to transplant rate vs 63% in Group X. One-year actuarial survival after transplant was 89% compared with 92% in patients without a ventricular assist device. There were no statistically significant laboratory parameters between Groups A and B identifying potential risk factors for poor outcome. Biventricular assist device therapy represents an effective and reliable means of supporting selected Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients as a bridge to transplantation, with excellent success to transplant rates and post-transplant survival.

Heart Transplantation in Children With a Fontan Procedure

Previous studies have reported that children with a prior Fontan procedure have decreased survival after heart transplantation. We examined 190 primary pediatric heart transplants. Since 1988, 27 (14.2%) of 190 children less than 18 years old undergoing primary heart transplantation had a Fontan procedure 3.7 ± 4.3 years before transplantation. Compared with 163 (85.8%) non-Fontan primary transplants, the Fontan patients were similar in age (8.2 ± 5.0 vs 6.5 ± 6.0 years), presensitization, and pretransplant clinical status. More Fontan patients had prior operations (100% vs 50%; p < 0.0001) and needed pulmonary artery reconstruction (100% vs 23.5%; p < 0.0001). Twelve (44%) had protein-losing enteropathy. Donor ischemic times (211 ± 72 vs 170 ± 61 minutes; p = 0.0018) and cardiopulmonary bypass times (197 ± 91 vs 121 ± 53 minutes; p < 0.0001) were greater in the Fontan group as were durations of ventilator support (4.9 ± 6.6 vs 2.6 ± 3.9 days; p = 0.018) and hospital stay (20.2 ± 17.5 vs 14.3 ± 12.4 days; p = 0.0435). The Fontan group had one 30-day mortality. One-year actuarial survival (81.5% vs 84.6%, Fontan vs non-Fontan) and five-year actuarial survival (65.5% vs 66.2%, Fontan vs non-Fontan) were similar, as was rejection incidence at one year (2.0 ± 2.0 vs 1.7 ± 1.9 episodes per patient; p = 0.3972). Five Fontan patients (18.5%) required retransplantation 4.9 ± 3.6 years posttransplant compared with 18 non-Fontan patients (11.0%) retransplanted 5.2 ± 3.4 years posttransplant (p = 0.3346). Contrary to prior reports, we did not identify any early or midterm disadvantage for children undergoing heart transplantation after a previous Fontan procedure despite more complex transplant operations. We contend that carefully selected children with a failing Fontan circulation can do as well as other children with heart transplantation.

Mesenchymal Stem Cell (MSC) Based Cord Blood (CB) Expansion (Exp) Leads to Rapid Engraftment of Platelets and Neutrophils

AbstractAbstract 362Delayed engraftment and low rates of platelet transfusion independence are frequently observed after CB transplantation (CBT). We conducted a study of ex-vivo co-culture of CB mononuclear cells with either third party haploidentical family member marrow derived MSCs (N=8) or off-the-shelf mesenchymal progenitor cells (MPCs) from Angioblast (N=24). Patients received a double cord blood transplant, with one of the 2 units undergoing ex vivo expansion using this system. MSCs create a microenvironment that promotes expansion and fosters the differentiation of hematopoietic cells. Patients must have had two CB units matched in at least 4/6 HLA antigens, with a minimum of 1×107 TNC/Kg per unit. Method:Diagnoses were AML/MDS (n=21), ALL (n=6), NHL (n=2), CLL (n=2), and HD (n=1). Fourteen patients (44%) were in CR (CR1, n=3, CR2 or more, n=11) and 18 (56%) had active disease at CBT. Preparative regimen: myeloablative fludarabine, melphalan, thiotepa and ATG (n=32), with rituximab in the 4 NHL/CLL cases. GVHD prophylaxis: tacrolimus and MMF. Median weight was 75.2 Kg (range, 15–118) and median age was 35.3 years (2.8-62 years). Donor-recipient HLA matching was 6 of 6 in 5%, 5 of 6 in 28% and 4 of 6 in 67% of the cases, respectively.Ex-vivo EXP: 100 ml of marrow was aspirated from the family donor and MSCs generated in ten T175 flasks, which took ∼21 days (n=8) or one vial of Angioblast MPCs was thawed and expanded to confluence in 10 flasks within 4 days (n=24). The CB unit with the lowest TNC dose was then thawed, divided into 10 fractions, and each placed into 1 flask containing the confluent layers of MSCs in expansion media with SCF, FLT3-ligand, G-CSF and TPO. After 7 days at 37°C, the non-adherent cells were removed from each flask, placed into each of ten one-liter Teflon-coated culture bags (American Fluoroseal) and cultured for an additional 7 days (14 days total), while 50 ml of media/growth factors was added to the flasks to culture the remaining adherent layer during that time period. On day 14 the cells from the bags and the flasks were combined, washed and infused along with a second unmanipulated CB unit. Result:The median number of total nucleated cell (TNC) and CD34+ cells infused/Kg in unmanipulated CB was 2.35 × 107 (range 0.2–8.2) and 0.95 × 105 (range 0–4). The median number of TNC and CD34+ cells infused/Kg after EXP was 5.8 × 107 (range, 0.3–14.4) and 8.7 × 105 (range, 0–93.4). This represented a median expansion of 14-fold (range 1–30) for TNC and 40-fold (range 4–140) for the CD34+ cells. Median time to neutrophil and platelet engraftment was 15 days (range 9–42) and 40 days (range 13–62). There were no toxicities attributable to the EXP cells. Thirty-one (97%) and 26 (81%) of all patients engrafted neutrophils and platelets, respectively. One patient died before engraftment. Thirty and one-hundred day non-relapse mortality is respectively 6% and 19%. Median donor(s) chimerism was 100% in the mononuclear, T lymphocyte and myeloid cell populations. On transplant day+21, EXP unit contributed with a mean of 19% of mononuclear cell, 16% of T cell, and 14% of myeloid chimerism. Subsequently, hematopoiesis was increasingly derived from the unexpanded unit with long-term engraftment provided by the unexpanded unit by six months posttransplant.Acute grade II-IV and III-IV GVHD rate was 50% and 16%; 25% of the grade II-IV GVHDs occurred beyond 100 days, and two patients developed chronic GVHD. With a median follow-up of 9 months, 11 patients are alive; actuarial one-year survival is 40%. Mortality was due to relapse in 26% and non-relapse causes in 74% of patients. Conclusion:MSC-CB Exp is feasible and leads to fast engraftment of neutrophils and platelets, and high-rates of platelet transfusion independence. Disclosures:No relevant conflicts of interest to declare.

Single daily dose of intravenous busulfan and melphalan as a conditioning regimen for patients with multiple myeloma undergoing autologous stem cell transplantation: a phase II trial

We evaluated the toxicity and outcome of a conditioning regimen comprising intravenous (iv) busulfan (BU) and melphalan (MEL) in 55 patients (median age, 61 years; range, 34–71) with multiple myeloma (MM) undergoing autologous stem-cell transplantation (ASCT). In 49 patients, this was the first ASCT. At transplant, 3 patients were in complete response (CR), 8 in near CR (nCR) and 30 in partial response (PR). The conditioning regimen comprised ivBU (3.2 mg/kg in a single daily dose, days −5 to −3) and MEL (140 mg/m2, day −2). Mucositis was the most frequent non-hematopoietic toxicity (47 patients). No patient developed sinusoidal occlusive syndrome. Febrile events were observed in 46 patients and were the cause of death in two (3.6%) transplant-related deaths. With a median follow-up of 15 months, 27 patients achieved CR/nCR (11 CR) and 21 a PR. The one-year actuarial overall and progression-free survival rates are 96% and 87%, respectively. This ivBU-containing regimen is associated with an acceptable toxicity and a high-response rate.

Induction Therapy With Thymoglobulin After Heart Transplantation: Impact of Therapy Duration on Lymphocyte Depletion and Recovery, Rejection, and Cytomegalovirus Infection Rates

This retrospective single-center study compared lymphocyte depletion in 144 heart transplant recipients using 2 different induction protocols with Thymoglobulin (Genzyme Transplant, Cambridge, MA). Thymoglobulin (1.5 mg/kg) was given to 105 patients for 7 days (Thymo7) and 39 patients for 5 days (Thymo5). Patient clinical characteristics were similar except that the Thymo7 group had a higher prevalence of women (33% vs 15%, p = 0.04), gender mismatch (35% vs 19%, p = 0.07), donor African American race (19% vs 2%, p = 0.008), older donor age (35 +/- 13 vs 31 +/- 12, p = 0.08), and higher pre-transplant creatinine (1.43 +/- 0.67 vs 1.25 +/- 0.48 mg/dl, p = 0.095). Seventy-five percent of the Thymo7 group reached target (absolute lymphocyte count <or=200) and 42% at 21 days (p = 0.002). Thymo7 patients had significantly lower rejection rates (>or=1B) within the first year (7% vs 22%, p = 0.02). No humoral rejection occurred. At 1 year, freedom from rejection was 93% in the Thymo7 group vs 80% in the Thymo5 group (p = 0.007), and cytomegalovirus disease (9% and 5%, p = 0.5) and bacterial infection (26% vs 32%, p = 0.5) were similar. One-year actuarial survival was 92% +/- 3% in the Thymo7 and 100% in the Thymo5 group (p = 0.07), and at 3 years, 85 +/- 4% and 90 +/- 6%, respectively (p = 0.4). Both Thymoglobulin regimens were well tolerated. The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.

Diagnosis and surgical therapy of lung metastases

Operations for pulmonary metastases were carried out on 33 patients from January 1st 1976 to December 31st 1985 at the Surgical Division, University of Cologne. In six cases each, the primary tumors were hypernephromas, colorectal carcinomas and osteocarcinoma. There were five cases of melanoma, three cases of testicular carcinoma, two cases of corpus carcinoma and two cases of soft-tissue sarcoma as well as one case each of parotid, tonsillar and laryngeal carcinoma. The large number of metastases could be determined in 21 cases (64%) by means of preoperative radiodiagnostics with X-rays of the chest in two planes, conventional tomography and computer tomography of the thorax. Computer tomography was the most efficient single investigation. 17 patients received atypical resection and lobectomy was carried out in 16 cases. For all patients, the cumulative survivals revealed a one-year actuarial survival of around 70% and a three-year actuarial survival of about 20%. Patients with several metastases (two to six) had a very much poorer prognosis than patients with solitary pulmonary metastases. There was no connection between the surgical technique selected and the expected survival time in any case. The tumor-free interval between operation on the primary tumor and resection of the pulmonary metastases only had a slight prognostic significance.

Laboratory based low dose combination chemotherapy + bevacizumab for recurrent refractory and unresectable gastric cancer

14133 Twenty consecutive prospectively registered patients with refractory or Stage IV gastric cancer were treated with GFLIP (Bruckner el al ASCO 2002;2005). The last 10 upon relapse were treated with GFL[OX]T and Bevacizumab, substituting oxaliplatin (OX) 30→40 mg/M2, taxotere (T) 30→40 mg/M2 for cisplatin in the q2wk schedule. One or both regimens produced; objective responses for 15 patients including 5 complete (radiologic, tumor markers, PET responses) and 2 surgical downstaging resulting in resection or successful completion surgery; 3 patients had stable disease greater than 4 months with subjective benefit, gemcitabine was given at 400→500 mg/M2 as tolerated (→), 2 failed both regimens. One-year actuarial survival was 75%, two-year survival was 25%. All 20 lived more than six months. The level of activity, multiple crossover responses, responses with both regimens, a number of long remissions (long survival after 5FU cisplatin and GFLIP failed) and clinical downstaging allowing further surgery identify both regimens either individually or in sequence as deserving systematic investigation. The utility of low doses (responses), unusual clinical benefits, quality of life and safety offer possible advantages compared to standard dose regimens.This strategy appears to reduce and delay the limiting toxicity of the irinotecan (I) 80 mg/M2, cisplatin (P) 40 mg/M2 OX/T which are conventionally treatment limiting drugs. The regimens were designed based on laboratory evidence of low dose drug interaction including reversal of resistance to conventional drugs (applicable to both pancreatic and gastric cancer (Janat et al, Amer Asso Cancer Res 1999). After clinical demonstrations of high response rates and reversal of resistance against refractory pancreatic cancer (Bruckner et al, AntiCancer Res and ASCO 2005). The regimens were offered to patients with recurrent previously treated and refractory gastric cancer and then based on initial exceptional responses to high risk patients with poor prognosis due to clinical complications of their gastric cancer. No significant financial relationships to disclose.

Living Donor Liver Transplantation: Early Single-Center Experience

Adult living donor liver transplantation (ALDLT) is an accepted procedure to overcome the organ shortage. The advantages of ALDLT must be balanced against the first concern of donor safety. We analyzed the results of our early experience among a series of eight ALDLT performed between April 2001 and October 2003. All patients were listed as United Network for Organ Sharing UNOS status 2b and 3. Transplant recipients consisted of four men and four women. The living donors included four sons, three daughters, and one son-in-law (ages 20 to 45 years). One donor was anti-HBc-positive and negative for hepatitis B virus-DNA by polymerase chain reaction analysis in serum and in liver tissue. GR/WR >0.8 and fatty liver <10% were considered suitable for the hepatectomy. Residual left lobe volume was at least 33%. No exogenous blood and blood products were transfused into the donors and a cell-saver device was used in all donors (blood loss 490 ± 160 mL). All procedures were right lobe hepatectomy; in one case the middle hepatic vein was withdrawn with the right graft. The mean ischemia time was 1.5 ± 0.5 hours. All donors survived the procedure. Median hospital stay was 8.5 ± 2.1 days in all donors but one who had a long stay because of drug-related hepatitis. One graft was lost and one donor aborted because of preoperative overestimated volumetry. Complications were experienced by two donors (25%). Five recipients (62.5%) experienced major complications; one patient underwent retransplantation because of donor graft loss. Two biliary and two vascular complications (33.3%) occurred in three patients. No perioperative death occurred. Two patients died at 9 and 10 months after transplant because of heart and respiratory failure in the first case and tumor recurrence in the second. One-year actuarial survival is 75%. ALDLT using right lobe has gained acceptance to overcome the organ shortage. Donor selection criteria must be stringent with respect to residual donor hepatic volume, steatosis, and liver function.

Successful ABO-incompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis

Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.

One Thousand Liver Transplants: The Hospital Clinic Experience

Objectives Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results. Patients and Methods With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period). Results Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively. Conclusions Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.