Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

Background We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer. Methods T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m² twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point. Results Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m² was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21. Conclusion Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.     

Evaluating the feasibility and uptake of a community‐led HIV testing and multi‐disease health campaign in rural Uganda

Introduction: Multi‐disease community health campaigns can be effective for population‐wide HIV testing in a research setting (SEARCH: NCT01864603). We sought to evaluate feasibility and uptake of a community‐led health campaign (CLHC) planned and implemented by village leaders and local clinic workers in Uganda. Methods: Over five months in 2014, locally elected village leaders and Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a census followed by a CLHC, after training by two SEARCH trial consultants and by leaders from a neighbouring parish that had previously participated in a SEARCH health campaign. We defined feasibility as: (1) elected leaders’ participation in training and implementation of pre‐campaign census and mobilization activities; (2) implementation of all campaign activities by MoH‐funded, local clinic staff; and (3) community participation in the campaign, including point‐of‐care screening for HIV, malaria, hypertension and diabetes, and same‐day referral for male circumcision and family planning (FP). Costing of all salaries and supplies was conducted. Results: Elected leaders from all eight villages in the parish participated in CLHC training. They and local clinic staff met monthly to select and plan CLHC services. Village leaders then leveraged existing volunteer health teams to perform a door‐to‐door census, enumerating 5,202 parish residents over 2 weeks. 2,753 (53%) residents participated in the 6‐day CLHC. Of 1,584 adult participants, 1,474 (93%) tested for HIV: 105/1,474 (7.1%) tested HIV positive. 27% (751/2,753) of participants reported fever and underwent malaria rapid diagnostic testing: 5.3% (40/751) tested positive. Among adults screened, 19% (271/1,452) were hypertensive, and 3% (18/637) had a random blood sugar >11.1 mmol/L. Of 805 men and boys (>10 years), 91 (11%) accepted same‐day clinic referral and underwent medical circumcision. Of 900 women offered same‐day long‐term FP referrals, 25 accepted. The CLHC cost, including census, mobilization and testing services, was $23,597 ($8.57/participant). C onclusions: Elected village leaders successfully planned and conducted a 6‐day multi‐disease health campaign with service provision by local clinic staff that reached over half of a rural Ugandan community. These data suggest it is feasible for local leaders and clinics to adopt a multi‐disease health campaign approach to scale‐up HIV testing in rural Africa.     

A reduced‐order stochastic observer approach to optimal state estimation with noise‐free measurements

In a continuous‐time Kalman filter, it is required that the measurement noise covariance be non‐singular. If the measurements are noise‐free, then this condition does not hold and, in practice, the measurement data are differentiated to define a derived measurement function to build what is known as Deyst filter. It is proposed here that a reduced‐order observer be used in deriving the linear minimum‐variance filter to construct state estimates based on the original measurement data with no need for differentiation. This filter is of dimension (n?p) where n and p are the state and measurement vector dimensions, respectively. In this work, we consider both the finite‐time and infinite‐time results. The set of all assignable estimation error covariances are characterized and the set of all estimator gains are parametrized in addition to the linear minimum variance optimal results. The conditions for the existence of the optimal steady‐state filter are obtained in terms of the system theoretic properties of the original signal model. A simple example is included to illustrate the effectiveness of the proposed technique. Copyright © 2001 John Wiley & Sons, Ltd.     

Risk of spinal cord ischemia after endograft repair of thoracic aortic aneurysms

BACKGROUND: Surgical repair of thoracoabdominal aneurysms may be associated with a significant risk of perioperative morbidity including spinal cord ischemia, which occurs at a rate of between 5% and 21%. Spinal cord ischemia after endovascular repair of thoracic aortic aneurysms (TAAs) has also been reported. This investigation reviews the occurrence of spinal cord ischemia after endovascular repair of descending TAAs at the Mount Sinai Medical Center. PATIENTS AND METHODS: Between May 1997 and April 2001, 53 patients underwent endovascular exclusion of their TAA. Preprocedure computed tomography scanning and angiography were performed on all patients. All were performed in the operating room using C-arm fluoroscopy. Physical examinations and computed tomography scans were performed at discharge and at 1, 3, 6, and 12 months postoperatively and then annually thereafter. Spinal cord ischemia developed in three of the 53 patients (5.7%) postoperatively. In one patient, cord ischemia developed that manifested as early postoperative left leg weakness occurring after concomitant open infrarenal abdominal and endovascular TAA repair. The neurologic deficit resolved 12 hours after spinal drainage, steroid bolus, and the maintenance of hemodynamic stability. The remaining two patients developed delayed onset paralysis, one patient on the second postoperative day and the other patient 1 month postrepair. Both of these patients had previous abdominal aortic aneurysm repair, and both required long grafts to exclude an extensive area of their thoracic aortas. Irreversible cord ischemia and paralysis occurred in both of these patients. CONCLUSIONS: Endovascular repair of TAA has shown a promising reduction in operative morbidity; however, the risk of spinal cord ischemia remains. Concomitant or previous abdominal aortic aneurysm repair and long segment thoracic aortic exclusion appear to be important risk factors. Spinal cord protective measures (ie, cerebrospinal fluid drainage, steroids, prevention of hypotension) should be used for patients with the aforementioned risk factors undergoing endovascular TAA repair.     

Recurrent peripheral embolism following nonunion of the clavicle

Vascular complications in closed clavicular fractures are uncommon, with an incidence of only 0.4%. Subclavian artery injury can present acutely or can have a delayed presentation with arm ischemia. We report the case of an undetected subclavian pseudoaneurysm in a patient with a nonunion fracture clavicle who was referred with persistent ischemia following attempted brachial embolectomy at another center, along with a review of literature to support the hypothesis that in addition to repair of the aneurysm, treatment of the psuedarthrosis by fixation of the clavicle is essential.     

Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.     

NLR is predictive of upstaging at the time of radical cystectomy for patients with urothelial carcinoma of the bladder

ObjectiveTo evaluate the ability of preoperative neutrophil-lymphocyte ratio (NLR) to predict pathologic upstaging and nonorgan-confined (NOC) (≥pT3) disease.Methods and materialsAfter institutional review board approval, the records of consecutive patients undergoing radical cystectomy (RC) for urothelial carcinoma from 2002 to 2012 at the University of Wisconsin Hospital were reviewed. A total of 102 patients with NLR within 100 days of surgery were eligible for analysis. The primary outcome was difference in stage from preoperative assessment to time of RC. Differences in preoperative NLR between groups were evaluated with an unequal variance t test. A univariate analysis assessed whether NLR, preoperative stage, grade, associated lymphovascular invasion, preoperative hydronephrosis, gender, previous pelvic radiotherapy, previous intravesical bladder cancer treatments, or nodal stage were related to upstaging. Multivariate analyses were performed to evaluate the relationship of NLR to upstaging and relative organ-confined (≤pT2) and NOC disease.ResultsOf 390 consecutive patients undergoing RC, 102 patients met study criteria. Overall, 55 (53.9%) patients were upstaged, 25 (25.5%) were unchanged, and 21 (20.6%) were downstaged. Fifty-one patients (50%) were upstaged to more advanced disease (≥pT3). NLR and preoperative hydronephrosis were significantly related to pathologic tumor staging. NLR, preoperative hydronephrosis, and preoperative tumor stage were significantly related to upstaging to NOC disease. Patients who were upstaged to≥pT3 demonstrated statistically significant greater NLRs (4.33±0.87) compared with patients who remained at≤pT2 stage (2.66±0.29) (P<0.001).ConclusionsPreoperative NLR is a simple measurement that can be used to identify high-risk patients who may be upstaged at the time of RC and may benefit from neoadjuvant chemotherapy.     

The Prognostic Significance of an R1 Resection in Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy

Background

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.

Methods

Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.

Results

A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.

Conclusions

A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.