Absolute rate constants for some intermolecular and intramolecular reactions of \u3b1-, \u3b2-, and \u3b3-silicon-substituted radicals

Rate constants for hydrogen atom abstraction from n-Bu 3GeH (k GeH) by Me 3SiCH 2 \u2022 (1 \u2022), Me 3SiCH 2CH 2 \u2022 (2 \u2022), and Me 3SiCH 2CH 2CH 2 \u2022 (3 \u2022) and from n-Bu 3SnH (k SnH) by 1 \u2022 and 3 \u2022 have been determined at ambient temperatures. The order of decreasing radical reactivity is 1 \u2022 > n-alkyl > 3 \u2022 > 2 \u2022. However, for bromine abstraction from the parent bromides by n-Bu 3Sn \u2022 and n-Bu 3Ge \u2022, the order of decreasing reactivity is 1-Br > 2-Br > 3-Br 3c n-alkyl bromide. The Arrhenius equations for reaction of 1 \u2022 and 3 \u2022 with n-Bu 3SnH were also determined: log (k SnH(1 \u2022)/(M -1 s -1)) = (10.2 \ub1 0.5) - (3.90 \ub1 0.62)/\u3b8 and log (k SnH(3 \u2022)/(M -1 s -1)) = (8.4 \ub1 0.7) - (2.81 \ub1 0.95)/\u3b8, where \u3b8 = 2.3RT kcal/mol. These kinetic data are discussed in relation to previously measured 8 rate constant ratios, k c 5+6/k SnH and k exo 5/k endo 6, where k c 5+6 corresponds to the cyclization of \u3b1-, \u3b2-, and \u3b3-dimethylsilyl-substituted 5-hexenyl radicals to form 5-membered (k exo 5) and 6-membered (k endo 6) silacycloalkylmethyl radicals. \ua9 1988 American Chemical Society.Peer reviewed: YesNRC publication: Ye

Is the turbidimetric immunoassay of haptoglobin phenotype-dependent?

Comparison of the turbidimetric immunoassay of haptoglobin with a reference method (the RID technique with appropriate correction for phenotype) clearly showed the turbidimetric assay to be phenotype-dependent. Correction factors for the three main phenotypes were calculated and reference values determined. The observed overall reference range of haptoglobin, irrespective of the phenotype, was 0.56–3.76 g/L. After correction for phenotype, reference values for the three types were: Hp 1-1: 0.77–2.49; Hp 2-1: 0.86–4.76; and Hp 2-2: 0.48–3.15 g Hp/L. From our reference values for the several phenotypes of haptoglobin it may be argued that phenotyping is desirable only when the uncorrected haptoglobin value, determined by turbidimetry, is within the range 0.38–0.98 g/L. Limited to hemolytic diseases, phenotype determination can be omitted beyond this range

Surgery of the primary in stage IV colorectal cancer with unresectable metastases

Item does not contain fulltextSurgery plays an important role in the treatment of patients with limited metastatic disease of colorectal cancer (CRC). Long term survival and cure is reported in 20-50% of highly selected patients with oligometastatic disease who underwent surgery. This paper describes the role of surgery of the primary tumour in patients with unresectable stage IV colorectal cancer. Owing to the increased efficacy of chemotherapeutic regimens in stage IV colorectal cancer, complications from unresected primary tumours are relatively infrequent. The risk of emergency surgical intervention is less than 15% in patients with synchronous metastatic disease who are treated with chemotherapy. Therefore, there is a tendency among surgeons not to resect the primary tumour in case of unresectable metastases. However, it is suggested that resection of the primary tumour in case of unresectable metastatic disease might influence overall survival. All studies described in the literature (n = 24) are non-randomised and the majority is single-centre and retrospective of nature. Most studies are in favour of resection of the primary tumour in patients with symptomatic lesions. In asymptomatic patients the results are less clear, although median overall survival seems to be improved in resected patients in the majority of studies. The major drawback of all these studies is that primarily patients with a better performance status and better prognosis (less metastatic sites involved) are being operated on. Another limitation of these studies is that few if any data on the use of systemic therapy are presented, which makes it difficult to assess the relative contribution of resection on outcome. Prospective studies on this topic are warranted, and are currently being planned. CONCLUSION: Surgery of the primary tumour in patients with synchronous metastasised CRC is controversial, although data from the literature suggest that resection might be a positive prognostic factor for survival. Therefore prospective studies on the value of resection in this setting are required

The Importance of a Minimal Tumor-Free Resection Margin in Locally Recurrent Rectal Cancer

Item does not contain fulltextBACKGROUND: The importance of the circumferential resection margin has been demonstrated in primary rectal cancer, but the role of the minimal tumor-free resection margin in locally recurrent rectal cancer is unknown. OBJECTIVE: The purpose of this work was to evaluate the prognostic importance of a minimal tumor-free resection margin in locally recurrent rectal cancer. DESIGN: This was a single-institution, retrospective study. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: Based on the final pathology report, surgically treated patients with locally recurrent rectal cancer between 1990 and 2013 were divided into 4 groups: 1) tumor-free margins of >2 mm, 2) tumor-free margins of >0 to 2 mm, 3) microscopically involved margins, and 4) macroscopically involved margins. MAIN OUTCOME MEASURES: Local control and overall survival were the main outcome measures. RESULTS: A total of 174 patients with a median follow-up of 27 months (range, 0-144 months) were eligible for analysis. There was a significant difference in 5-year local re-recurrence-free survival in favor of 41 patients with tumor-free margins of >2 mm compared with 34 patients with tumor-free margins of >0 to 2 mm (80% vs 62%; p = 0.03) and a significant difference in 5-year overall survival (60% vs 37%; p = 0.01). The 5-year local re-recurrence-free and overall survival rates for 55 patients with microscopically involved margins were 28% and 16%, and for 20 patients with macroscopically involved margins the rates were 0% and 5%. On multivariable analysis, tumor-free margins of >0 to 2 mm were independently associated with higher re-recurrence rates (HR, 2.76 (95% CI, 1.06-7.16)) and poorer overall survival (HR, 2.57 (95% CI, 1.27-5.21)) compared with tumor-free margins of >2 mm. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Resection margin status is an independent prognostic factor for re-recurrence rate and overall survival in surgically treated, locally recurrent rectal cancer. In complete resections, patients with tumor-free resection margins of >0 to 2 mm have a higher re-recurrence rate and a poorer overall survival than patients with tumor-free resection margins of >2 mm

Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer

Item does not contain fulltextPURPOSE: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. METHODS AND MATERIALS: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (</=2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. RESULTS: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM </= 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) CONCLUSION: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM

Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor

Item does not contain fulltextBACKGROUND: The widespread use of neoadjuvant radiotherapy (nRTx) followed by total mesorectal excision (TME) introduced the problem of treating locally recurrent rectal cancer (LRRC) after nRTx and TME. Few data exist on the outcome of the surgical treatment of this type of LRRC and the influence of nRTx for the primary tumor on the outcome is unclear. METHODS: All patients receiving multimodality treatment (including intraoperative radiotherapy) for LRRC in our center between 1996 and 2012 were analyzed retrospectively. The outcome of patients with nonmetastasized resectable LRRC who received nRTx and TME for the primary tumor was compared to the outcome of patients who did not receive nRTx for the primary tumor. RESULTS: During this period, 139 patients underwent surgery for LRRC; 93 of these patients underwent curative surgery for LRRC after TME for the primary tumor. Sixty-five patients did not receive nRTx for the primary tumor, whereas 28 patients received nRTx for the primary tumor. There were no significant differences in the number of incomplete resections or perioperative morbidities. There was no significant difference in 5-year overall survival (28 vs. 43%, p = 0.81), recurrence-free survival (55 vs. 48%, p = 0.5), and disease-free survival (27 vs. 40%, p = 0.59). CONCLUSIONS: Surgical treatment of carefully selected patients with nonmetastasized resectable LRRC after nRTx and TME for the primary tumor is feasible and can result in sustained local control and overall survival. Patients with resectable LRRC who received nRTx for the primary tumor do not have a poorer outcome than patients who did not

Long-Term Results of Tumor Necrosis Factor {alpha}- and Melphalan-Based Isolated Limb Perfusion in Locally Advanced Extremity Soft Tissue Sarcomas

Item does not contain fulltextPURPOSE Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor alpha (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS. PATIENTS AND METHODS We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors. Results The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%. CONCLUSION We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered

Long-term results of the "liver first" approach in patients with locally advanced rectal cancer and synchronous liver metastases

Item does not contain fulltextBACKGROUND: There are no reports available on the long-term outcome of patients with the "liver first" approach. OBJECTIVES: The aim of this study was to present the long-term results of the "liver first" approach in our center. DESIGN: This study is a retrospective analysis. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Patients from May 2003 to March 2009 were included. INTERVENTIONS: Patients with locally advanced rectal cancer and synchronous liver metastases were first treated for their liver metastases. If the treatment was successful, patients underwent neoadjuvant chemoradiotherapy and surgery for the rectal cancer. If metastases could not be resected, resection of the rectal primary was not routinely performed. MAIN OUTCOME MEASURES: The primary outcome measured was long-term results of the "liver first" approach. RESULTS: Of the 42 patients included (median age, 61 years), all but one (98%) started with neoadjuvant chemotherapy. In total, 31 (74%) patients completed the "liver first" approach. In 11 patients, curative therapy was not possible because of unresectable metastases; in 10 of these patients (91%), the primary tumor was not resected. LIMITATIONS: This study was limited because it was a retrospective analysis without a control group. CONCLUSIONS: By applying the "liver first" approach, the majority of this group of patients (74%) could undergo curative treatment of both metastatic and primary disease in combination with optimal neoadjuvant therapy. This strategy may avoid unnecessary rectal surgery in patients with incurable metastatic disease. In this selected patient group, long-term survival may be achieved with a 5-year survival rate of 67%

Prediction of tumor stage and lymph node involvement with dynamic contrast-enhanced MRI after chemoradiotherapy for locally advanced rectal cancer.

Item does not contain fulltextPURPOSE: The usefulness of restaging by magnetic resonance imaging (MRI) after chemoradiotherapy (CTx/RTx) in patients with locally advanced rectal cancer has not yet been established, mostly due to the difficult differentiation between viable tumor and fibrosis. MRI with dynamic contrast-enhanced (DCE) sequences may be of additional value in distinguishing malignant from nonmalignant tissue. The aim of this study was to assess the accuracy of tumor, nodal staging, and circumferential resection margin (CRM) involvement by MRI with DCE sequences after CTx/RTx. METHODS: The accuracies were assessed by MRI on T2-weighted magnetic resonance (MR) images with DCE sequences in patients with locally advanced rectal cancer after a long course of CTx/RTx. MR images were assessed by two independent radiologists. RESULTS: For tumor staging and CRM involvement, MRI with DCE sequences had an accuracy of 45 and 60 %, respectively. The accuracy for nodal staging was 93 %. On MRI, malignant lymph nodes had a median diameter of 8 mm (range, 4-18) and benign lymph nodes a median diameter of 4 mm (range, 3-11). A significant indicator for benign nodes was hypointensity on T2-weighted images (p < 0.001) and early complete arterial phase enhancement on DCE-weighted images (p < 0.001). A significant indicator for malignant nodes was heterogeneity on T2-weighted images (chi (2), p < 0.000) and early incomplete arterial phase enhancement on DCE (p < 0.001). CONCLUSIONS: MRI with DCE is a useful tool for nodal staging after CTx/RTx. The addition of DCE sequences did not improve the accuracy of determining the tumor stage, CRM involvement, and in detecting complete response.1 april 201