Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer.

BACKGROUND: The optimal timing of surgery following preoperative chemoradiotherapy (CRT) is controversial. This trial aimed to compare pathological complete response (pCR) rates obtained after an interval of 8 weeks or less versus more than 8 weeks. METHODS: Patients with locally advanced rectal adenocarcinoma situated within 12 cm of the anal verge (T3-4 or N+ disease) were randomized to undergo total mesorectal excision (TME) within 8 weeks (classical interval, CI group) or after 8 weeks (long interval, LI group) following CRT. RESULTS: Among the 327 included patients (CI 160, LI 167), the pCR rate was significantly higher in the LI group than in the CI group (10·0 versus 18·6 per cent; P = 0·027). The highest pCR rate (29 per cent) was observed between 10 and 11 weeks. There was statistically significant disease regression in the LI group, with better stage (P = 0·004) and T category (P = 0·001) than in the CI group. There was no significant difference in surgical quality (rates of tumour-positive margins, TME quality, anastomotic leakage and intraoperative perforation) between the groups. The overall morbidity rate was 22·5 per cent in the CI group and 19·8 per cent in the LI group (P = 0·307). Regression analysis including sex, age, clinical stage, tumour location, tumour differentiation, TME quality, concomitant chemotherapy and interval to surgery revealed no statistically significant predictors of pCR. CONCLUSION: Disease regression and pCR rate are increased with an interval between CRT and surgery exceeding 8 weeks. Registration number: NCT03287843 (http://www.clinicaltrials.gov).

A comparison of the femur heads histomorphometrically regarding trabecular bone properties in the patients with osteoporosis and osteoarthritis.

The purpose was to compare the bone samples histomorphometrically regarding trabecular bone properties in the patients with osteoarthritis (OA) and osteoporosis (OP). Femoral head specimens were obtained from 18 patients with OA and 17 patients with femoral neck fracture due to OP during hip arthroplasty. Histomorphometric analyses were performed by soft ware program (Carl Zeiss) to measure trabecular area (Tb.a, mm(3)), trabecular thickness (Tb.th, µm) and trabecular separation (Tb.s, µm). In the results, Tb.a and Tb.th values were significantly lower (p < 0.05), Tb.s was higher in the patients with OP (p < 0.05). Bone metabolism parameters were different between the groups (p < 0.05). All histomorphometric parameters were highly correlated with the BMDs (p < 0.01). This study showed inverse relation between OA and OP regarding trabecular bone properties, BMD and bone turnover metabolism markers. The strong relations between results suggest that either BMDs or bone turnover markers can be used for prescience of the fractures.

Incidence and importance of c4d deposition in renal allograft dysfunction.

Recent studies showed that peritubular capillary deposition of C4d is a marker of humoral immune responses directed against a renal allograft. The aim of this retrospective study was to investigate the incidence, clinical features, and prognostic implications of C4d deposition in renal allograft biopsy specimens. The biopsies had been performed due to acute graft dysfunction. This study of 104 renal allograft biopsies performed in 2004 classified histopathological findings according to Banff criteria. All paraffin-embedded biopsy samples were stained with an immunohistochemical method for C4d deposition. Demographic data, clinical findings, and biochemical findings were obtained from patients' charts. C4d staining was positive in 15/104 (14%) samples. The staining pattern was diffuse in 8 and focal in 7 patients. Nine patients were males. The overall mean age was 33 +/- 6 years. Ten received live-donor grafts. The biopsy occurred at a mean of 1007 +/- 1415 (range, 15-4712) days after the operation with a mean serum creatinine (SCr) level of 2.8 +/- 1.5 (1.25-6.0) mg/dL. Patients were divided into 2 groups according to the occurrence time: early (before 100 days) and late (after 100 days). Among the early group (n = 5), the mean SCr level was 2.8 +/- 1.5 mg/dL; a diffuse staining pattern was seen in 4 (80%) patients. Histological findings were acute rejection in 3, borderline changes in 1, or thrombotic microangiopathy in 1 patient. Two patients were treated with pulse steroids and 3 with ATG, intravenous immunoglobulin, and plasmapheresis. Three patients lost their grafts at the mean of 118 +/- 100 days after the biopsy. In the late group (n = 10), the mean SCr level was 2.8 +/- 1.7 mg/dL with a diffuse staining pattern in 4 (40%) patients. The histological findings included acute rejection in 6, chronic vascular rejection in 2, thrombotic microangiopathy in 1, and chronic allograft nephropathy in 1 patient. Six patients were treated with pulse steroids, and 3 with ATG and intravenous immunoglobulin. Five patients lost their grafts at a mean of 200 +/- 270 days. The overall incidence of C4d deposition was 14%; it was seen both in the early and late posttransplantation period. Although a diffuse staining pattern was more frequently seen in the early period, C4d deposition indicated a poor allograft prognosis in both periods. Introduction of C4d staining into the routine may guide more specific treatments directed toward the humoral alloresponse.