Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response

Introduction: Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. Patients and methods: Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1–1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20 mg/m² d1–d5 and etoposide 50 mg/m² d1–d5, d1–5 d29–33. Within 3–4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4–6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20–25 Gy boost ±1 extra-cycle of cisplatinum + etoposide. Results: From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median = 26.7 months) for all the intention-to-treat population (n = 107), 62% and 51% (median = 36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median = 19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio = 0.50 and 0.48, p = 0.006 and 0.038, respectively). Conclusion: Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0–1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.     

Long-term follow-up of percutaneous vena cava filters: a prospective study in 100 consecutive patients.

OBJECTIVES: the long-term outcome in following insertion of inferior vena cava (IVC) filters remains unclear. DESIGN: prospective study. MATERIAL AND METHODS: one hundred consecutive patients received percutaneous vena cava filters between 1988 and 1993. The patients underwent clinical examination, abdominal X-rays and duplex ultrasound of the IVC, right internal jugular vein and legs after a mean follow-up duration of 38+/-11 months. RESULTS: forty patients died after implantation (median 11.3 months; IQR: 1.8--20.4 months). The cause of death was known in 33 cases, and pulmonary embolism (PE) was suggested in three. Multivariate analysis revealed the mortality rate to be significantly higher in cancer patients (relative risk of 2.13). The 3-year survival was 20% for cancer patients and 71% for patients without cancer. Among the 60 living patients, thrombi were trapped in the filter in 10 cases, the filter tilted in four, was malpositioned in five and migrated in 29. These incidents were recorded as asymptomatic complications, as opposed to seven IVC thromboses and 23 recurrent lower limb thromboses, which were considered as symptomatic complications. CONCLUSION: long-term major complications are not frequent. As expected, cancer was the only factor predicting mortality. IVC filters seem effective in preventing PE.     

Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans

Fructose has been shown to have a catalytic effect on glucokinase activity in vitro; however, its effects on hepatic glycogen metabolism in humans is unknown. To address this question, we used (13)C nuclear magnetic resonance (NMR) spectroscopy to noninvasively assess rates of hepatic glycogen synthesis and glycogenolysis under euglycemic (approximately 5 mmol/l) hyperinsulinemic conditions (approximately 400 pmol/l) with and without a low-dose infusion of fructose (approximately 3.5 micromol. kg(-1). min(-1)). Six healthy overnight-fasted subjects were infused for 4 h with somatostatin (0.1 micromol. kg(-1). min(-1)) and insulin (240 pmol. m(-2). min(-1)). During the initial 120 min, [1-(13)C]glucose was infused to assess glycogen synthase flux followed by an approximately 120-min infusion of unlabeled glucose to assess rates of glycogen phosphorylase flux. Acetaminophen was given to assess the percent contribution of the direct and indirect (gluconeogenic) pathways of glycogen synthesis by the (13)C enrichment of plasma UDP-glucuronide and C-1 of glucose. In the control studies, the flux through glycogen synthase and glycogen phosphorylase was 0.31 +/- 0.06 and 0.17 +/- 0.04 mmol/l per min, respectively, and the rate of net hepatic glycogen synthesis was 0.14 +/- 0.05 mmol/l per min. In the fructose studies, the glycogen synthase flux increased 2.5-fold to 0.79 +/- 0.16 mmol/l per min (P = 0.018 vs. control), whereas glycogen phosphorylase flux remained unchanged (0.24 +/- 0.06; P = 0.16 vs. control). The infusion of fructose resulted in a threefold increase in rates of net hepatic glycogen synthesis (0.54 +/- 0.12 mmol/l per min; P = 0.008 vs. control) without affecting the pathways of hepatic glycogen synthesis (direct pathway approximately 60% in both groups). We conclude that during euglycemic hyperinsulinemia, a low-dose fructose infusion causes a threefold increase in net hepatic glycogen synthesis exclusively through stimulation of glycogen synthase flux. Because net hepatic glycogen synthesis has been shown to be diminished in patients with poorly controlled type 1 and type 2 diabetes, stimulation of hepatic glycogen synthesis by this mechanism may be of potential therapeutic value.     

Reverse total shoulder arthroplasty: a review of results according to etiology

BACKGROUND: Reverse total shoulder arthroplasty provides a surgical alternative to standard total shoulder arthroplasty for the treatment of selected complex shoulder problems. The purpose of the present study was to evaluate the effects of etiology on the results of reverse total shoulder arthroplasty. METHODS: Between May 1995 and June 2003, 240 consecutive reverse total shoulder arthroplasties were performed in 232 patients with an average age of 72.7 years. Patients were grouped according to etiology, and the clinical and radiographic outcomes for each group were measured and compared. RESULTS: One hundred and eighty-six patients with 191 retained reverse total shoulder arthroplasty prostheses were followed for an average of 39.9 months. Overall, the average Constant score improved from 23 points before surgery to 60 points at the time of follow-up and 173 of the 186 patients were satisfied or very satisfied with the result. Although substantial clinical and functional improvement was observed in all etiology groups, patients with primary rotator cuff tear arthropathy, primary osteoarthritis with a rotator cuff tear, and a massive rotator cuff tear had better outcomes, on average, than patients who had posttraumatic arthritis and those managed with revision arthroplasty. Dislocation (fifteen cases) and infection (eight cases) were the most common complications among the 199 shoulders that were followed for two years or were revised prior to the minimum two-year follow-up. Patients who received the reverse prosthesis at the time of a revision arthroplasty had a higher complication rate than did those who received the reverse prosthesis at the time of a primary arthroplasty. CONCLUSIONS: The reverse total shoulder arthroplasty prosthesis can produce good results when used for the treatment of a number of other complex shoulder problems in addition to cuff tear arthropathy. Patients with posttraumatic arthritis and those undergoing revision arthroplasty may have less improvement and higher complication rates in comparison with patients with other etiologies. The advanced age of the patients in the present series and the relatively short duration of follow-up suggest that the prosthesis should continue to be used judiciously.     

Influence of preservation solution on human islet isolation outcome

BACKGROUND: The influence of the preservation solution used for in situ perfusion of the donor and pancreas storage on islet isolation has received little attention. METHODS: In this prospective controlled trial, we compared the outcome of human islet isolation from pancreata perfused with University of Wisconsin (UW) solution or Celsior, an alternative colloid-free extracellular solution. RESULTS: At the 1-year interim analysis, the viability and insulin secretion of islets isolated from donors perfused with UW (n=19) or Celsior (n=5) were identical. However, total islet recovery (IEQ) and isolation yield (IEQ/g) were 1.8-fold and 2.1-fold inferior in the Celsior group (P<0.05 vs. UW). Overall, 13 (68%) of islet preparations were effectively transplanted from the UW group vs. none from the Celsior group (P=0.01). The clinical study was discontinued and the causes of these differences were further explored in the pig (n=14). In contrast to UW, Celsior induced cell swelling and pancreas edema after only four hours of cold storage. These abnormalities were delayed when the donor was perfused with Solution de Conservation d'Organes et de Tissus (SCOT), an extracellular solution containing polyethylene glycol. CONCLUSIONS: Our results suggest that colloid-free preservation solutions might be suboptimal for pancreas perfusion and cold storage prior to islet isolation and transplantation. Because pancreata are now frequently recovered for islet transplantation, preliminary experimental and clinical data about islet isolation should be obtained prior to the routine implementation of new preservation solutions for abdominal perfusion during multiorgan recovery.     

Correlation between groin pain and cup design of hip-resurfacing implants: a prospective study

Purpose

Cup design has been incriminated as the source of groin pain after hip resurfacing but has not been well described; thus, it was assessed in a prospective study looking at three implant types.

Methods

A group-match was done between three groups of hip resurfacing devices according to age, sex, body mass index, activity level, osteoarthritis aetiology and pre-operative scores.

Results

The global groin pain rate was 5.7 % at six months and 2.7 % at last follow-up. Groin pain rate was significantly different between the three groups (p = 0.004) and had a strong influence on the subjective results (p = 0.04). No groin pain emerged between six months and last follow-up. No clinical differences were noted in Harris hip score and Merle d’Aubigné-Postel score at last follow-up. However, the Oxford hip score and Devane activity score were significantly lower for cups with macrostructures.

Conclusion

The low groin pain rate in this prospective cohort was probably secondary to the specific surgical technique used and seems to be correlated with cup design. Macrostructures on the external part of the cup could be significantly harmful.     

Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma

Background

Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.

Methods

Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.

Results

Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3–5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2–4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).

Conclusions

Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.     

Prospective Evaluation of an Extended 21-Core Biopsy Scheme as Initial Prostate Cancer Diagnostic Strategy

Background

The debate on the optimal number of prostate biopsy core samples that should be taken as an initial strategy is open.

Objective

To prospectively evaluate the diagnostic yield of a 21-core biopsy protocol as an initial strategy for prostate cancer (PCa) detection.

Design, setting, and participants

During 10 yr, 2753 consecutive patients underwent a 21-core biopsy scheme for their first set of biopsy specimens.

Intervention

All patients underwent a standardized 21-core protocol with cores mapped for location.

Outcome measurements and statistical analysis

The PCa detection rate of each biopsy scheme (6, 12, or 21 cores) was compared using a McNemar test. Predictive factors of the diagnostic yield achieved by a 21-core scheme were studied using logistic regression analyses.

Results and limitations

PCa detection rates using 6 sextant biopsies, 12 cores, and 21 cores were 32.5%, 40.4%, and 43.3%, respectively. The 12-core procedure improved the cancer detection rate by 19.4% (p = 0.004), and the 21-biopsy scheme improved the rate by 6.7% overall (p < 0.001). The six far lateral cores were the most efficient in terms of detection rate. The diagnostic yield of the 21-core protocol was >10% in prostates with volume >70 ml, in men with a prostate-specific antigen level < 4 ng/ml, with a prostate-specific antigen density (PSAD) <0.20 ng/ml per gram. A PSAD <0.20 ng/ml per gram was the strongest independent predictive factor of the diagnostic yield offered by the 21-core scheme (p < 0.001). The 21-core protocol significantly increased the rate of PCa eligible for active surveillance (62.5% vs 48.4%; p = 0.036) than those detected by a 12-core scheme without statistically increasing the rate of insignificant PCa (p = 0.503).

Conclusions

A 21-core biopsy scheme improves significantly the PCa detection rate compared with a 12-core protocol. We identified a cut-off PSAD (0.20 ng/ml per gram) below which an extended 21-core scheme might be systematically proposed to significantly improve the overall detection rate without increasing the rate of detected insignificant PCa.     

Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function benefit even when expanding indications beyond the traditional 4-cm cutoff

ObjectivesTo analyze to what extent partial nephrectomy (PN) is superior to radical nephrectomy (RN) in preserving renal function outcome in relation to tumor size indication.Methods and materialsClinical data from 973 patients operated at 9 academic institutions were retrospectively analyzed. Glomerular filtration rate (GFR) before and after surgery was calculated with the abbreviated Modification of the Diet in Renal Disease equation. For a fair comparison between the 2 techniques, all imperative indications for PN were excluded. A shift to a less favorable GFR group following surgery was considered clinically significant.ResultsMedian age at diagnosis was 60 years (19–91). Tumor size was smaller than 4 cm in 665 (68.3%) cases and larger than 4 cm in 308 (31.7%) cases. PN and RN were performed in 663 (68.1%) and 310 (31.9%) patients, respectively. In univariate analysis, patients undergoing PN had a smaller risk for developing significant GFR change following surgery than those undergoing RN did. This was true for tumors≤4 cm (P = 0.0001) and for tumors>4 cm (P = 0.0001). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P = 0.0001), preoperative GFR<60 ml/min (P = 0.0001), tumor size≥4 cm (P = 0.0001), and older age at diagnosis (P = 0.0001).ConclusionsThe renal function benefit carried out by elective PN over RN persists even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cutoff.     

Long-term changes in mouse lung following inhalation of a fibrosis-inducing dose of 239PuO2: changes in collagen synthesis and degradation rates.

Mice were exposed by nose-only inhalation to 239PuO2, which resulted in an IAD of 1110 +/- 29 Bq. At various times after exposure, rates of collagen metabolism were measured using validated in vivo methods based on the administration of radiolabelled proline, together with a large flooding dose of unlabelled proline and measurement of its incorporation into lung collagen as hydroxyproline. Dramatic increases in both synthesis and degradation rates of collagen were observed. At 54 days after exposure the fractional synthesis rates in experimental mice were almost five times those in controls (control: 3.2 +/- 0.6%/day, 239PuO2-exposed: 14.5 +/- 0.4%/day) and by 300 days synthesis rates, although declining, were still more than double the control values. A similar pattern of change was observed for collagen degradation. The combination of changes in synthesis and degradation rates led to a 60% increase in lung collagen content by 300 days (control: 3.05 +/- 0.24 mg/lung, 239PuO2-exposed: 4.88 +/- 0.42 mg/lung). The data suggest that extensive remodelling of the lung connective tissue matrix occurs during development of fibrosis and that, over long periods of time, small imbalances between synthesis and degradation may result in quite large increases in protein content.