Fluoride pharmacokinetics and changes in Lumbar spine and hip bone mineral density

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examin the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm² (range 0.69 to 0.99) at baseline to 0.88 g/cm² (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range −1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm² (0.62 to 0.94) at baseline to 0.69 g/cm² (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of −2% (−19 to 10). BMD at the other hip sites also decreased alightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.     

Thoracoscopic and laparoscopic lymph node staging in esophageal cancer: do clinicopathological factors affect the outcome?

Background. This study was performed to evaluate the pattern of lymphatic metastases found by combined thoracoscopic (TS) and laparoscopic (LS) lymph node staging in esophageal cancer, and ascertain whether clinicopathologic factors may be used to guide the clinical practice of combined TS and LS staging.

Methods. A retrospective study was performed in a series of 76 esophageal cancer patients who had undergone both TS and LS staging before treatment. The correlation of TS and LS lymph node metastases with clinicopathologic factors was analyzed, including the clinical T stage, clinical N stage, tumor location, and histology.

Results. Thirty-one patients (40.8%) were found to have lymphatic metastasis by TS and LS staging. Among them, 22 patients had abdominal lymph node metastases, 7 patients had mediastinal lymph node metastases, and 2 patients had both. Patients with advanced T stage (T3 to T4) or adenocarcinoma had a higher frequency of abdominal lymphatic metastases than patients with early T stage (T1 to T2) (39% vs 16%; p = 0.04) or squamous cell carcinoma (39% vs 20%; p = 0.079), respectively. Patients with clinical abdominal N1 stage had a higher incidence of positive laparoscopic finding than patients with clinical abdominal N0 stage (67% vs 23%; p = 0.001). There was no significant correlation between lymphatic metastases and the location of the primary tumor.

Conclusions. Clinicopathologic factors, including the histologic type, the clinical T stage, and abdominal N stage, may affect the outcome of TS and LS lymph node staging in esophageal cancer patients. This clinicopathologic impact may play a role for the selection of candidates for TS and LS staging, and also allows surgeons to focus their attention on the most likely high-yield biopsy targets.     

Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 ± 1.5 years (x ± SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 ± 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 ± 0.22 vs. −0.12 ± 0.25, +0.03 ± 0.19 vs. −0.54 ± 0.24, and +0.08 ± 0.14 vs. −0.02 ± 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 ± 0.04 vs. 0.40 ± 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (−2.1 ± 1.1 vs. +7.0 ± 3.3 μg/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 ± 2.5% vs. −0.3 ± 1.4%, and +8.1 ± 4.7 vs. −0.9 ±1.7, after 10.3 ± 0.4 and 17.3 ± 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.     

Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer Decreases Distant Recurrence and Could Eradicate Local Recurrence

Background

The aim of this study was to evaluate the clinical implications of pathologic complete response (pCR) (i.e., T0N0M0) after neoadjuvant chemoradiation and radical surgery in patients with locally advanced rectal cancer.

Materials and Methods

A single-center, prospectively maintained colorectal cancer database was queried for patients with primary cII and cIII rectal cancer staged by CT and ERUS/MRI undergoing long-course neoadjuvant chemoradiation followed by proctectomy with curative intent between 1997 and 2007. Patients were stratified into pCR and no-pCR groups and compared with respect to demographics, tumor and treatment characteristics, and oncologic outcomes. Outcomes evaluated were 5-year overall survival, disease-free survival, disease-specific mortality, local recurrence, and distant recurrence.

Results

The query returned 238 patients (73% male), with a median age of 57 years and median follow-up of 54 months. Of these, 58 patients achieved pCR. Patients with pCR vs no-pCR were statistically comparable with respect to demographics, chemoradiation regimens, tumor distance from anal verge, clinical stage, surgical procedures performed, and follow-up time. No patient with pCR had local recurrence. Overall survival and distant recurrence were also significantly improved for patients achieving pCR.

Conclusions

Achievement of pCR after neoadjuvant chemoradiation is associated with greatly improved cancer outcomes in locally advanced rectal cancer. Future studies should evaluate the relationship between increases in pCR rates and improvements in cancer outcomes in this population.     

Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival

Background. This study was undertaken to determine the predictive value of nodal status at resection in regards to long-term outcome of patients undergoing neo-adjuvant therapy and resection for stage IIIA N2-positive non-small cell lung cancer (NSCLC).

Methods. We reviewed the medical records of all patients found on surgical staging to have N2-positive NSCLC and who underwent induction therapy followed by resection between 1988 and 1996 at our hospital. Complete follow-up information was examined utilizing Kaplan-Meier survival analysis and Cox proportional hazards multivariate analysis.

Results. One hundred three patients (59 men) with stage IIIA N2-positive NSCLC received neoadjuvant therapy before surgical resection. Preoperative therapy consisted of platinum-based chemotherapy (76), radiotherapy (18), or chemoradiation (9). Operations included pneumonectomy (38), bilobectomy (6), and lobectomy (59). There were four deaths and seven major complications. Eighty-five patients were followed until death. Median survival among 18 living patients is 60.9 months (range 29 to 121 months). Twenty-nine patients were downstaged to N0 and had 5-year survival of 35.8% (median survival 21.3 months). Seventy-four patients with persistent tumor in their lymph nodes (25 N1 and 49 N2) had significantly worse, 9%, 5-year survival, p = 0.023 (median survival 15.9 months). Other negative prognostic factors were adenocarcinoma and pneumonectomy.

Conclusions. Patients with N2-positive NSCLC whose nodal disease is eradicated after neoadjuvant therapy and surgery enjoy significantly improved cancer-free survival. These data support surgical resection for patients downstaged by induction therapy; however, patients who are not downstaged do not benefit from surgical resection. Direct effort should be made to improve the accuracy of restaging before resection.     

Clinical implications of acellular mucin pools in resected rectal cancer with pathological complete response to neoadjuvant chemoradiation1

Aim Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation achieve a pathological complete response (pCR), which is associated with an improved oncological outcome. However, in a proportion of patients with a pCR, acellular pools of mucin are present in the surgical specimen. The aim of this study was to evaluate the clinical implications of acellular mucin pools in patients with rectal adenocarcinoma achieving a pCR after neoadjuvant chemoradiation followed by proctectomy. Method A single‐centre colorectal cancer database was searched for patients with clinical Stage II and Stage III rectal adenocarcinoma who achieved a pCR (i.e. ypT0N0M0) after neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. Patients were categorized according to the presence or absence of acellular mucin pools in the resected specimen, and groups were compared. Patient demographics, tumour and treatment characteristics, and oncological outcomes were recorded. Primary outcomes were 3‐year local and distant recurrences, and disease‐free and overall survivals. Results Two hundred and fifty‐eight patients with clinical Stage II or Stage III rectal adenocarcinoma were treated by neoadjuvant chemoradiation. Fifty‐eight of these patients had a 58 pCR. Eleven of the 58 patients with a pCR had acellular mucin pools in the surgical specimen. The median follow up was 40 months. The groups were statistically similar with respect to demographics, chemoradiation regimens, distance of tumour from the anal verge, clinical stage and surgical procedure. No patient had local recurrence. Patients with acellular mucin pools had increased distant recurrence (21%vs 5%), decreased disease‐free survival (79%vs 95%) and decreased overall survival (83%vs 95%) rates, although none of these differences was statistically significant. Conclusion The presence of acellular mucin pools in a proctectomy specimen with a pCR does not affect local recurrence, but may suggest a more aggressive tumour biology.     

Partial left ventriculectomy: which patients can be expected to benefit?

Background. Although some patients with end-stage heart disease will benefit from a partial left ventriculectomy, no criteria have been found for identifying this group preoperatively. Our experience with partial left ventriculectomy at two institutions—the Texas Heart Institute in Houston, TX, USA, and Dedinje Cardiovascular Institute in Belgrade, Yugoslavia—showed a higher survival rate and better postoperative myocardial function in the Yugoslavian patients.

Methods. We reviewed data from 42 patients (21 at each center) who had idiopathic cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm, wall thickness of 1 cm or greater, and New York Heart Association class III or IV symptoms. The only significant difference in preoperative status between the two groups was duration of symptoms. Histologic specimens, blinded as to origin, were graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis. Computer-assisted myocyte and nuclear morphometry was also performed.

Results. Immediately postoperatively, there were no significant intergroup differences in the reduction in cardiac dimension or in corrections of mitral regurgitation. During 6-month follow-up, however, the Texas Heart Institute patients had a lower cardiac index (1.8 versus 3.0 L·min⁻¹·m⁻²; p = 0.001) and left ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje Cardiovascular Institute patients. The Texas Heart Institute patients differed from the Dedinje Cardiovascular Institute patients in the degree of severe or moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte diameter (35 ± 7 μm versus 27 ± 4 μm; p = 0.0002) and median nuclear size (15 ± 4 μm versus 12 ± 2 μm; p = 0.0029).

Conclusions. In the Texas Heart Institute patients, the significant intergroup difference in clinical outcome may have been related to increased myocyte hypertrophy and fibrosis. Further studies should be performed to determine the usefulness of these criteria in selecting patients for partial left ventriculectomy.     

CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer

BACKGROUND: The staging of esophageal cancer is imprecise. Thoracoscopic/laparoscopic (TS/LS) staging has been proposed as a more accurate lymph node (LN) staging method. We report the experience of an Intergroup NCI trial (CALGB 9380) evaluating the feasibility and accuracy of this staging modality. PATIENTS AND METHODS: From February 1995 to September 1999, 134 patients were entered in the study. This study represents the analysis of final data on 113 patients. TS/LS was considered feasible if TS and 1 LN sampled at least 3 LN by LS; a confirmed positive node was found; or T4 or M1 disease was documented. If this was accomplished in more than 70% of patients, TS/LS was believed to be feasible. RESULTS: The LN stations most frequently sampled in the thorax (134 patients) were levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9 (55%), and 10 (43%) and in the abdomen levels 17 (70%) and 20 (55%). The frequency of positive LN by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7 (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). Noninvasive tests (computed tomographic scan, magnetic resonance imaging, esophageal ultrasound scan) each incorrectly identified TN staging as noted by missed positive or false-negative LN or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of patients, respectively. Median operating time was 210 minutes (range, 40 to 865 minutes). Median postoperative hospital stay was 3 days (range, 1 to 35 days). There were no deaths or major complications. Seventy-three percent of patients met the definition for feasibility. In 30 patients TS was not feasible. Positive LN disease was found in 43 patients; 32 were deemed N0. Ten patients had T4/M1 disease. Of the 32 potentially resectable N0 patients, 14 patients had preoperative induction therapy; 13 patients went directly to operation with N0 confirmed in 9 patients, NX in 1 and N1 in 3. Three patients were unresectable, 1 patient died, and 1 was lost to follow-up. CONCLUSIONS: In summary, the feasibility of TS/LS was confirmed. It doubled the number of positive LNs identified by conventional, noninvasive staging. The overall accuracy remains to be defined by analysis of the LN negative group in follow-up. Although the positive predictive value was high, further study is warranted to confirm the role of TS/LS in the staging algorithm of esophageal cancer.     

Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer

OBJECTIVE: To evaluate the utility of F-FDG-PET in predicting response to concomitant chemoradiation in locally-advanced esophageal cancer. SUMMARY BACKGROUND DATA: Approximately 25% of esophageal cancer patients experience a pathologic complete response (pCR) to preoperative chemoradiation therapy. Computed tomography, endoscopy, and endoscopic ultrasound are unable to identify patients experiencing a pCR. Growing evidence supports the use of F-FDG-PET in the staging of esophageal cancer in its ability to detect occult metastatic and lymph nodal disease. The identification of patients with a pCR to chemoradiation could potentially spare those patients the morbidity associated with a resection. METHODS: Eligibility criteria included T3-T4N0M0 or T1-T4N1M0 esophageal cancer. Patients underwent an initial F-FDG-PET before treatment and then repeated 4 to 6 weeks after chemoradiation, prior to the esophagectomy. Chemoradiation consisted of: cisplatinum, 5-fluorouracil, and radiation to a median dose of 50.4 Gy. Pathologic response was determined from a systematic review of the esophagectomy specimens. RESULTS: Sixty-four patients have completed therapy to date. Response was as follows: pCR 27%, pathologic residual microscopic (pCRmicro) 14.5%, partial response 19%, and stable or progressive disease 39.5%. A pretreatment standardized uptake value (SUVmax1hour) > or = 15 was associated with an observed 77.8% significant response (pCR + pCRmicro) compared with 24.2% for patients with a pretreatment SUVmax1hour < 15 (P = 0.005). Significant response was observed in 71.4% of patients with a decrease in SUVmax1hour > or = 10 compared with 33.3% when the SUVmax1hour decreased <10 (P = 0.004). CONCLUSIONS: Pretreatment and posttreatment F-FDG-PET can be useful for predicting significant response to chemoradiation in esophageal cancer. These data should be considered in evaluation of patients for esophagectomy after chemoradiation.     

Comparison of outcomes between living donor and cadaveric lung transplantation in children

Background. Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL).

Methods. Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36 ± 3.16 years in LL and 12.00 ± 4.19 years in CL patients (p = 0.37, ns).

Results. There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48 ± 3.84 months) than LL (13.60 ± 10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV₁) (p = 0.001) and FEF_25–75% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL.

Conclusions. Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.     

Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using 18FDG-PET/CT

Background

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15?C30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC.

Methods

This is a retrospective review of patients with EUS-staged T3?CT4, N?+?rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002?C2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan?CMeier estimation evaluated significant predictors of survival.

Results

Seventy patients (age 62?years; 42M:28F) with preoperative stage T3 (n?=?61) and T4 (n?=?9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P?=?0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P?=?0.01). Median SUV decrease was 63% (7.5?C95.5%) and predicted pCR (P?=?0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50?days) than those without (P?=?0.02). Patients with post-CRT SUV?P?=?0.03). Patients with SUV decrease ??63% had improved overall survival at median follow-up of 40?months than those without (P?=?0.006).

Conclusions

PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV?相似文献   

Squamous Cell Carcinoma of the Esophagus: Multimodal Therapy in Locally Advanced Disease

The aim of this prospective study is to report our experience in the multimodal management of locally advanced esophageal squamous cell carcinoma (LAESC; stage III cTNM), focusing on the results of chemoradiotherapy followed by surgery. These findings were compared to the results of a standard group of patients with locally advanced esophageal carcinoma (LAEC; stage III pTNM) treated in our center with surgery alone. Sixty-one patients with LAESC underwent preoperative chemoradiotherapy (5-fluorouracil + cisplatin) with concomitant 45 Gray radiotherapy in a 5-week course. Transthoracic esophagectomy was performed 4 to 5 weeks after the end of the neoadjuvant therapy. Thirty-eight patients underwent surgery, and 37 of them had resections (resectability: 97% in the multimodal group; 84% in the standard surgical series; p = 0.07). The R0 (complete) resection rate was 78% compared to 56% in the standard surgical group (p <0.03). Eleven patients had no residual tumor in the resected specimen (pathologic complete response: pCR: 30%). The operative mortality rate was 19% compared with 8.8% in the standard series. The overall median survival of the resected patients was 21 months, with a 5-year survival rate of 11% (14% in the surgical group; NS). The 3-year and 5-year survival rates were 34% for the pCR group and respectively 5% and 0% for the group with pathologic incomplete response (pIR; p <0.05). The median survival was 28 months for the pCR patients and 19 months for the pIR group. In this non-randomized trial, preoperative chemoradiotherapy in LAESC seems to increase the resectability and R0 resection rates, to allow a higher pCR rate and a longer survival only in the pCR group, at the expense of an inadequate increase in operative mortality. This multimodal treatment cannot be proposed as a standard procedure unless less toxic regimens are developed, increasing the benefits with better local and distant failure control and decreasing operative mortality.     

Effectiveness of Image-Guided Radiotherapy for Locally Advanced Rectal Cancer

Background

Image-guided radiotherapy (IGRT) combines precise target visualization with optimal delivery of radiation dose to spare normal tissue from radiation and may potentially reduce side-effects and long-term treatment complications. We have assessed the effectiveness of IGRT for locally advanced rectal cancer.

Methods

A retrospective review of 22 patients with locally advanced rectal cancer who underwent preoperative chemoradiation was conducted.

Results

Nineteen patients (median age, 69 years) underwent surgical resection after chemoradiation. All 19 patients achieved complete resection with negative margins. Seven patients (32%) had no residual tumor in the surgical specimen. One patient had grade 4 gastrointestinal toxicity and hematological toxicity probably related to inadvertent overdosing of capecitabine. The median survival for the whole group—patients who had pCR and those who did not have pCR—was 14, 17, and 15 months, respectively.

Conclusions

Image-guided radiotherapy provided effective treatment for locally advanced rectal cancer with minimal toxicity and should be investigated in future prospective trials.     

Comparison of clinical results for unilateral and bilateral thoracoscopic lung volume reduction

Background. It is widely believed that bilateral thoracoscopic lung volume reduction (BTLVR) yields superior results when compared with unilateral thoracoscopic lung volume reduction (UTLVR) with regard to spirometry, functional capacity, oxygenation and quality of life results.

Methods. To address these issues, we compared the results of patients undergoing UTLVR (N = 338 patients) and BTLVR (N = 344 patients) from 1993 to 1998 at five institutions. Follow-up data were available on 671 patients (98.4%) between 6 and 12 months after surgery, and a patient self-assessment was obtained at a mean of 24 months.

Results. It was found that BTLVR provides superior improvement in measured postoperative percent change in FEV₁ (L) (UTLVR 23.3% ± 55.3 vs BTLVR 33% ± 41, p = 0.04), FVC(L) (10.5% ± 31.6 vs 20.3% ± 34.3, p = 0.002) and RV(L) (−13% ± −22 vs −22% ± 17.9, p = 0.015). BTLVR also provides a slight improvement over UTLVR in patient’s perception regarding improved quality of life (UTLVR 79% vs BTLVR 88%, p = 0.03) and dyspnea relief (71% vs 61%, p = 0.03). There was no difference in mean changes in Po₂ (mm Hg) (UTLV 4.5 ± 12.3 vs BTLVR 4.9 ± 13.3, p = NS), 6-minute walk (UTLVR 26% ± 66.1 vs BTLVR 31% ± 59.6, p = NS) or decreased oxygen utilization (UTLVR 78% vs BTLVR 74%, p = NS).

Conclusions. These data suggest that both UTLVR and BTLVR yield significant improvement, but the results of BTLVR seem to be superior with regard to spirometry, lung volumes, and quality of life.     

Isolated tumor cells in bone marrow predict reduced survival in node-negative non-small cell lung cancer

Background. It recently became evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate.

Methods. For tumor cell detection in the bone marrow, we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT_1–4, pN_0–2, M₀, and R₀ after a median follow-up of 66 months (range 48 to 74 months).

Results. Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3 to 18 months after surgery. In patients without histopathological lymph node metastases (pN₀; n = 66), the occurrence of 2 or more tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the 6 patients with a positive cytokeratin status after surgery developed a tumor recurrence 11 to 44 months after the operation, while none of the patients with a negative bone marrow at all time intervals showed a tumor relapse.

Conclusions. Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or reappearance of tumor cells in bone marrow indicates that these are not only shedded cells but rather represent true micrometastasis.     

Breast Cancer Subtypes can be a Predictor of Pathologic Complete Response and Survival in the Neoadjuvant Setting for T4 Noninflammatory Breast Cancer

Background: The aim of this study is to identify whether the breast cancer subtypes are predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and survival in patients with T4 noninflammatory breast cancer.

Methods: The records of 181 patients treated with anthracycline ± taxane based NAC followed by mastectomy and radiation therapy ± hormonotherapy were evaluated. The role of intrinsic subtypes of the tumor including luminal A, luminal B, HER2, and triple-negative on pCR and survival were analyzed.

Results: The median follow-up was 44 months (range:16–82 months). All patients received a median four cycles of NAC. Twenty-three patients (12.7%) were found to have pCR. In the univariate analysis, the intrinsic subtypes of the tumor had significant effect on pCR (p < 0.01). Also, intrinsic subtypes were significant predictors of pCR to NAC in the multivariate analysis (p < 0.01; hazard ratio, 2.4; 95% confidence interval, 1.1–6.8). While patients with triple-negative tumors had the highest rate of pCR (29%), this rate was the lowest in patients with HER2 tumors (4.2%). Five-year DFS was also significantly lower in patients with triple-negative (24%) and HER2 (21%) tumors compared to luminal A (61%) subtype (p < 0.0001). Likewise, 5-year OS was poorer in patients with triple-negative tumors (30%) and HER2 tumors (%31) compared to both luminal A (70%) and luminal B (68%) subtypes (p < 0.0001).

Conclusions: It can be concluded that breast cancer subtyping defines the extent of response to NAC and has a significant effect on survival in patients with T4 noninflammatory breast cancer.     

Thoracic metastasectomy in thyroid malignancies

Background. Relatively little evidence exists to guide the decision pathway regarding thoracic metastasectomy for thyroid malignancy.

Methods. Single-institution 10-year review.

Results. Sixteen patients had surgical treatment for intrathoracic metastatic thyroid malignancy: 12 men and 4 women, mean age 43.7 years (range 19 to 77). Histopathologic type was papillary in 6 cases, follicular in 4, Hürthle cell in 3, and medullary in 3. Indication was either “bulky” disease (8 patients) or poor response to radiotherapy (8 patients). We performed 11 sternotomies and five thoracotomies. Operative mortality was 6.25%. Operative morbidity was 6.25%. Mean survival was 39.5 months (0 to 144). Nine patients died during follow-up (mean survival of 41.2 months). Six patients survived, 4 free of disease (mean survival 70 months) and 2 with further relapse (mean survival 17 months). Five-year survival was 32.5%.

Conclusions. The cohort studied is one of the largest in the literature on the topic. Surgical treatment achieved a reasonable survival in a small subgroup of patients where radiotherapy had failed or was deemed inappropriate because of the size or location of the tumor. Further follow-up and more observations will be required for evaluating these preliminary findings.     

Preliminary experience with the St. Jude Medical Regent mechanical heart valve in the aortic position: early in vivo hemodynamic results

Background. The St. Jude Medical Regent is a new generation mechanical aortic valve.

Methods. Between March 2000 and July 2001, this valve was implanted in the aortic position in 40 patients (21 men; mean age 59.1 ± 9.0 years). Preoperatively, 24 patients (60%) were in New York Heart Association functional class III or IV. Eighteen patients (45%) underwent associated procedures. Mean valve size was 21.4 ± 2.4 mm. The mean duration of follow-up was 8.5 ± 4.5 months (range, 1 to 16 months).

Results. There were no operative deaths. Early complications included one reoperation for bleeding and one transient low output syndrome. Valve replacement was followed by a significant reduction in mean and peak transaortic gradients over time (p < 0.001) and analysis of variance failed to demonstrate statistical differences between valve size over time (p = not significant). A significant reduction in left ventricular hypertrophy occurred over time (p = 0.01) in all valve sizes (p = not significant between groups): baseline left ventricular mass index was 194 g/cm²; it reduced by 22 g/cm² (p = 0.006) at discharge. Left ventricular mass index decreased from 172 ± 55 g/cm² to 156 ± 44 g/cm² (p = 0.03) from discharge to 2 months. Further reductions were not significant. Relative wall thickness decreased from 0.57 ± 0.13 preoperatively to 0.42 ± 0.06 at discharge (p = 0.001), and again at 2 months (−0.2; p = not significant), and at 1 year (−0.02; p = not significant).

Conclusions. The early experience with the St. Jude Medical Regent valve has been satisfactory.     

Hydrogen peroxide for prevention of bacterial growth on polymer biomaterials

Background. Despite widespread use of potent antibiotics, infections of artificial implants and catheters are of increasing concern. We tested whether local treatment with 3% hydrogen peroxide (H₂O₂), long known as an inexpensive wound disinfectant, could prevent or reduce bacterial growth on polymer biomaterials.

Methods. Two-centimeter-long pieces of polyurethane and silicone tubing were contaminated with a standardized solution of Staphylococcus epidermidis (10⁵/mL) and then rinsed and wiped with saline (0.9%) solution. Bacterial growth was assessed after incubation at 37°C for 24 hours. Bacterial colonies were compared for the following treatments: wiping only with saline; wiping with 1.5%, 2%, or 3% H₂O₂; pretreating biomaterials with 3% H₂O₂ and subsequent contamination for 2 and 4 hours without treatment after contamination; and contamination of tubings 1 month after pretreatment with 3% H₂O₂. The effect of 3% H₂O₂ was also assessed on contamination with Escherichia coli.

Results. Bacterial growth was reduced by more than 99% when the contaminated tubes were treated with 3% H₂O₂ compared with saline control (p < 0.001). Lower concentrations of H₂O₂ were less effective. The length of the contamination period had no influence on the effectiveness of H₂O₂ when used on polyurethane but did with silicone tubings. Pretreatment with H₂O₂ 1 month before contamination still reduced bacterial growth rate by 90% on polyurethane and by 75% on silicone tubings. Comparable effects on bacterial growth rate were observed for staphylococci (−90%, p < 0.001) and escherichiae (−90%, p < 0.001).

Conclusions. Local treatment with 3% H₂O₂ significantly reduced bacterial growth on polymer biomaterials even for 1 month after treatment. This finding might influence clinical strategies of prevention of foreign body infection.