[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies].

OBJECTIVE: To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies. METHODS: Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×107 total nucleated cells/kg and (2.4 ± 1.0)×105 CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×109/L was (20 ± 5) days and the average time of platelet ≥ 20×109/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively. CONCLUSIONS: The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.

Comparison between thoracoscopic and open approaches in thymoma resection.

BACKGROUND: To investigate the feasibility and indications of video-assisted thoracic surgery (VATS) in thymoma resection. METHODS: The clinical data of 103 patients undergoing thymoma resection via different approaches [including conventional lateral thoracotomy approach (LTA) in 41 cases, median sternotomy approach (MSA) in 40 cases, and right-sided VATS in 22 cases] were analyzed. Among them, 59, 13, 25, and 6 patients were in Masaoka stage I, II, III, and IV, respectively. Myasthenia gravis (MG) was also found in 54 cases. The patients were followed up for postoperative survival and the improvement in MG. The prognostic indicators of patients undergoing thymoma resection via different surgical approaches (i.e., LTA, MSA, and VATS) were statistically analyzed. RESULTS: Eight of 103 patients died. Six patients underwent unilateral sacral nerve resection, among whom 4 patients developed respiratory dysfunction, and 3 died. Two patients died of MG after surgery, 1 patient died of tumor recurrence and metastasis, 1 patient died of heart disease, and the cause of death was unknown in the remaining patient. The drainage time was shorter in VATS group than in open groups, along with smaller tumor size. The VATS group also had shorter hospital stay in the whole series and the subgroup without accompanying MG. The improvement in MG showed no significant difference among the three surgical groups. Both 5- and 10-year survival rates were 91% in the entire cohort. CONCLUSIONS: VATS is like a conventional surgeries for improving MG in thymoma patients with accompanying MG. VATS resection can still be considered for thymoma that only invades the mediastinal pleura. For thymomas that have intact capsules and have not invaded mediastinal pleura, MSA surgery shall be performed to ensure patient safety if the anteroposterior diameters of the tumors are large and the masses have produced severe compression of the innominate vein, even if the tumors are still in the Masaoka stage II. For thymomas with large left-to-right diameters and with most parts of the tumors located in the left thoracic cavity, a left-sided approach (either VATS or an open approach) may be used in the absence of MG; if MG accompanies the condition, an MT approach or a bilateral VATS may be considered. In patients with unilateral pericardial phrenic nerve and/or local pericardial involvement, right-sided VATS thymectomy may be considered for thymomas located at the right side and bilateral VATS surgery can be performed for tumors located at the left side. In summary, VATS is feasible for the treatment of thymoma complicated by MG. VATS can be performed in patients with Masaoka stage I, II and (a certain portion of) III thymoma; for some patients with Masaoka stage II thymoma, especially those with compression of the innominate vein, the use of VATS should be cautious.

[The clinical results of right ventricular outflow tract reconstruction with a transannular patch of autologous pericardium].

OBJECTIVE: To evaluate the application value of simultaneous enlargement of the pulmonary annulus and the pulmonary cusp with a transannular patch of autologous pericardium in right ventricular outflow tract (RVOT) reconstruction. METHODS: Thirty-two patients who had complex congenital heart diseases received the technique between Jan. 2003 and Dec. 2005. Two surgical approaches were developed to construct a competent neocusp with autologous pericardium that could be extended through the pulmonary valve annulus or valve commissures. RESULTS: There was only 1 early death. The postoperative complications occurred in 6 patients recovered uneventfully. The results of the 4 approximately 40 month follow-up in 31 patients showed good motion of reconstructed cusps. 17 patients had no or trivial pulmonary insufficiency. There was mild insufficiency in 12 patients and moderate insufficiency in 2. None of these patients needed reoperations. CONCLUSION: The surgical technique of simultaneous enlargement of the pulmonary annulus and the pulmonary cusp with a transannular patch of autologous pericardium is a safe, reliable and effective way for RVOT reconstruction. However, further close follow-up is needed to determine the true value of this technique.

Testin is a tumor suppressor in non-small cell lung cancer.

The Testin gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. It has been implicated in several types of cancers including prostate, ovarian, breast and gastric cancer. In the present study, we investigated the function of the candidate tumor-suppressor Testin gene in non-small cell lung cancer (NSCLC). In NSCLC cell lines, we observed lower expression of Testin compared to that noted in normal human bronchial epithelial cells. MTT assays, flow cytometry, clonogenic assay and invasion assay showed that the overexpression of the Testin gene inhibited cancer cell proliferation, invasion and colony formation. In tumor xenograft models, Testin markedly inhibited lung cancer cell xenograft formation and growth in athymic nude mice. Taken together, these data suggest that Testin plays an important role in the development and progression of NSCLC. Testin may be an effective novel target in NSCLC prevention and treatment.

Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode.

Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.

[Unrelated cord blood transplantation in adult patients with hematologic malignancies].

OBJECTIVE: To analyse the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies. METHODS: Twenty eight consecutive adult patients with hematological malignancies were treated with UCBT and 20 of them were advanced-stage diseases. Double or multiple UCB grafts were used for 18 patients, while single UCB graft for 10 patients. Myeloablative conditioning regimens were given to 26 cases and nonmyeloablative regimens to 2 cases. All patients were given a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. RESULTS: Median time to neutrophil engraftment (≥ 0.5 × 10(9)/L) in 26 patients was 18 (14 - 37) days and platelet engraftment (≥ 20 × 10(9)/L) in 22 patients was 30 (25 - 49) days. Chimerism was weekly assessed by PCR analysis of short tandem repeat (STR) sequences in whole blood or bone marrow and 22 cases were confirmed of fully donor chimeric from 7 to 21 days after transplantation. Eighteen cases developed acute GVHD, greater than grade II in 1, and 6 of 22 patients who survived more than 100 days developed limited chronic GVHD. Eighteen cases were alive in hematologic remission at a median follow-up of 9.5 (2.5 - 72.0) months. The probability of event-free survival at 3 years was 56.7%. Two cases relapsed and 8 of 10 cases died of transplant related complications. CONCLUSIONS: UCBT could be safely and effectively used for adult patients with hematologic malignancies. Use of double UCB units is a strategy extending the feasibility of UCBT.

[Expression and abscission of activated receptors and their ligands on/from NK cells in peripheral blood of patients with acute leukemia].

This study was aimed to explore the immune escaping mechanisms based on expression and abscission of human natural killer (NK) cell activating receptors NKG2D and their ligands MICA/B, ULBP-1, 2, 3 in patients with acute leukemia (AL). 30 de novo AL patients and 10 healthy persons (control) were enrolled in study. Flow cytometry was used to detect the expression levels of MICA/B, ULBP-1, 2, 3 on leukemic cells. ELISA was used to detect the levels of soluble MICA (sMICA), solube MICB (sMICB) and soluble ULBP-1, -2, -3 in the serum. The results showed that sMICA, sMICB and ULBP-1, -2, -3 were not expressed or expressed at very low levels on leukemia cells of the patients; the levels of free sMICA and sMICB in serum of AL patients were higher than that in serum of healthy persons, there was significant difference (p<0.01). But the levels of ULBP 1-3 in serum of AL patients did not show obvious statistical difference as compared with healthy persons (p>0.05). It is concluded that the negative or low expression of NKG2D ligands (MICA, MICB and ULBPs) on surface of acute leukemia cells may lead to the immune escape of leukemia cells, the abscission of MICA and MICB, and the deficiency of ULBP expression on leukemia cells may be one of immune escape mechanisms of leukemia cells.

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT. METHODS: To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA. RESULTS: All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 10(9)/L and platelet counts greater than 20 × 10(9)/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%. CONCLUSION: HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.

[Therapeutic effect of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens on hematological malignancies].

This study was aimed to investigate the therapeutic efficiency and complications after allo-hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning regimens in hematologic malignancies. 10 patients (6 CML patients, 2 AML patients, 1 ALL patient and 1 NHL patient) underwent related allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens. The conditioning regimens consisted of "FLU + CY + TBI" basically and was appropriately improved in accordance with status of patients. Cyclosporin A (CsA) and mycophenolate mofetil (MMF) were used to prevent the graft-versus-host disease (GVHD). Detection of bone marrow cells, chromosomes, fused gene, ABO blood group and STR-PCR were used to observe engraftment, relapse, GVHD, transplantation- related complications (TRC) after transplantation and to evaluate patients quality of life. The results showed that the 10 patients successfully accepted the transplantation and their primary diseases were cured. In one patient, severe pulmonary infection happened, and in another one CMV infection occurred. Grade IV of acute GVHD occurred in one case and grade I of acute GVHD in 2 cases, the no chronic GVHD appeared. 5 patients relapsed after transplantation at various time points, the donor lymphocytes infusion (DLI) or drugs rescued these 5 patients. During median follow-up of 5 - 35 months, 2 out of which died, 8 survived, the overall survival rate was 80%, and the survivors live in a high-quality life. In conclusion, the hematopoietic stem cell transplantation with reduced intensity conditioning regimens was feasible with relatively low toxicity for recipients. GVHD and TRC were low, and life quality of patients after transplantation was high. DLI could cure the primary diseases even relapsed after transplantation.

Simultaneous enlargement of the pulmonary annulus and the pulmonary cusp with autologous pericardium in right ventricular outflow tract reconstruction.

BACKGROUND: Surgical repair of obstructive lesions of the right ventricular outflow tract (RVOT) commonly creates pulmonary valve incompetence, which continues to stimulate research for the optimal materials and surgical techniques to reconstruct RVOT. In this study, we present the early results with simultaneous enlargement of the pulmonary annulus and the pulmonary cusp with a transannular patch of autologous pericardium in RVOT reconstruction. PATIENTS AND METHODS: From January 2003 to December 2005, the surgical technique of simultaneous enlargement of the pulmonary annulus and the pulmonary cusp was used in 32 patients who had complex congenital heart anomalies with pulmonary artery hypoplasia. The functional status of the patients was followed up in the cardiologic clinic of our institute. The motion of the newly constructed valve and the degree of pulmonary insufficiency were evaluated by echocardiography before discharge and at 2-6 months, 12 months, and 36 months postoperatively. RESULTS: Early death occurred in one patient (3.1%). Postoperative complications occurred in six patients but they recovered uneventfully. During the follow-up, 28 of 31 operative survivors were in New York Heart Association functional class I without medication and the other three were in class II. Seventeen patients had no or trivial pulmonary regurgitation; mild regurgitation was present in 12 patients, and moderate regurgitation was seen in 2 patients. None of these patients needed reoperation and echocardiography showed good motion of the reconstructed valve. CONCLUSIONS: The surgical technique of simultaneous enlargement of the pulmonary annulus and the pulmonary cusp with a transannular patch of autologous pericardium is a safe, reliable, and effective way for RVOT reconstruction. Satisfactory early results have been achieved; however, long-term follow-up is necessary to determine the true value of this technique.