High-dose thiotepa,melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.     

The impact of donor age and sex on the nucleated cell count and CD34 count in healthy bone marrow donors

BM remains an important source of stem cells. The BM characteristics change with age but the estimation of CD34 calculation of one CD34+ cell per 100 nucleated cells is used for all donors including pediatric donors in the operating room before getting the actual CD34 count. In order to see whether this formula is applicable for pediatric donors, we designed a retrospective study to see the affect of the age and sex on the BM NCC, CD34 count, and CD34/NCC ratios. Ninety‐eight BM collections from 91 related donors were evaluated retrospectively (median age: nine yr [1.5–54 yr]; M/F: 41/50). A significant negative correlation was found between the donor age and NCC (r = −0.229, p < 0.05), CD34 count (r = −0.563, p < 0.01), and CD34/NCC (r = −0.664, p < 0.01). The negative correlation for CD34 count and CD34/NCC persisted in female and male donor groups. When donors younger than 16 yr of age were compared with the older donor group, the median NCC, median CD34 count, and CD34/NCC were significantly lower in the older group (p < 0.01). Age and sex have to be taken into consideration to avoid unnecessary high‐volume collections and increased operating room time in the younger donors.     

Patients' perspectives on the management of emotional distress in primary care settings

Objective  To investigate how important treatment for emotional distress is to primary care patients in general and to primary care patients with depression, and to evaluate the types of mental health interventions they desire. Design  Patient surveys. Setting  Five private primary care practices. Measurements and main results  Patients' desire for treatment of emotional distress and for specific types of mental health interventions were measured, as well as patients' ratings of the impact of emotional distress, the frequency of depressive symptoms, and mental health functioning. Of the 403 patients, 33% felt that it was “somewhat important” and 30% thought it was “extremely important” that their physician tries to help them with their emotional distress. Patient desire for this help was significantly related to a diagnosis of depression (P<.001), perceptions about the impact of emotional distress (p<.001), and mental health functioning (p<.001). Among patients with presumptive diagnoses of major and minor depression, 84% and 79%, respectively, felt that it was at least somewhat important that they receive this help from their physician. Sixty-one percent of all primary care patients surveyed and 89% of depressed patients desired counseling; 23% of all patients and 33% of depressed patients wanted a medication; and 11% of all patients and 5% of depressed patients desired a referral to a mental health specialist. Conclusions  A majority of these primary care patients and almost all of the depressed patients felt that it was at least somewhat important to receive help from their physician for emotional distress. The desire for this help seems to be related to the severity of the mental health problem. Most of the patients wanted counseling, but relatively few desired a referral to a mental health specialist. Funded by grant R01 MH51067 from the National Institute of Mental Health.     

Does Prior Abdominal Surgery Influence Conversion Rates and Outcomes of Laparoscopic Right Colectomy in Patients with Neoplasia?

Purpose  The study investigated the impact of prior abdominal surgery on conversions and outcomes of laparoscopic right colectomy. Methods  A consecutive series of 414 patients with cancer or adenomas who underwent a laparoscopic right colectomy from March 1996 to November 2006 were studied for surgical conversions and outcomes. Conversion was defined as an incision length > 7 cm. Results  Patients with prior abdominal surgery (n = 191) were compared with patients with no prior abdominal surgery (n = 223), and showed no significant differences in age, ASA classification, length of stay, operative time, blood loss, harvested nodes, tumor size, and specimen length. Significantly more wound infections occurred in the prior abdominal surgery group (22 vs.12, P = 0.023). Body mass index > 30 showed a three-fold increased risk of conversion. Fifteen percent of the no prior abdominal surgery patients and 17 percent of the prior abdominal surgery patients were converted (P > 0.05). Conversion was associated with a longer mean length of stay (8.8 days) relative to laparoscopically completed cases (6.3 days) regardless of prior abdominal surgery history (P < 0.0001). Conclusions  Laparoscopic right colectomy for neoplasia was not associated with a higher conversion rate or morbidity in patients with prior abdominal surgery. Prior abdominal surgery is not a contraindication to laparoscopic right colectomy. Presented at the 15th International Congress of the European Association of Endoscopic Surgery, Athens, Greece, July 4 to 7, 2007.     

Bone marrow mesenchymal stem cells enhance bone formation in orthodontically expanded maxillae in rats

Objective:To transplant bone marrow–derived mesenchymal stem cells (MSCs) into the interpremaxillary suture after rapid maxillary expansion with the aim of increasing new bone formation in the suture.Materials and Methods:Nineteen male Wistar rats were divided into two groups (control, n  =  9; experimental, n  =  10). Both groups were subjected to expansion for 5 days, and 50 cN of force was applied to the maxillary incisors with a helical spring. Pkh67⁺ (green fluorescent dye)–labeled MSCs were applied to the interpremaxillary suture after force application into the interpremaxillary suture of rats. Bone formation in the sutural area was histomorphometrically evaluated, including the amount of new bone formation (µm²), number of osteoblasts, number of osteoclasts, and number of vessels. Mann-Whitney U-test was used for statistical evaluation at the P < .05 level.Results:After 10 days of retention, Pkh67⁺ can be detected in suture mostly in the injection site under fluorescence microscope. Histomorphometric analysis revealed that a single local injection of MSCs into the midpalatal suture increased the new bone formation in the suture by increasing the number of osteoblasts and new vessel formation, compared with controls injected with phosphate-buffered saline.Conclusions:This preclinical study might provide foundations for the underlying potential clinical use of MSCs after maxillary expansion. Given the fact that MSCs are currently in use in clinical trials, this approach might be a feasible treatment strategy to accelerate new bone tissue formation in midpalatal suture and to shorten the treatment period for patients undergoing maxillary expansion reinforcement     

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non–small-cell lung cancer (NSCLC) with uniformly ¹³C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in ¹³C₆-glucose or ¹³C₅,¹⁵N₂-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.