Assessment of the effect of interval from presentation to surgery on outcome in patients with peri-ampullary malignancy

BackgroundDelay between diagnosis of peri-ampullary cancer (PC) and surgery may allow tumour progression and affect outcome. The aim of this study was to explore associations of interval to surgery (IS) with pathological outcomes and survival in patients with PC.MethodA database review of all patients undergoing surgery between 2006 and 2014 was undertaken. IS was measured from diagnosis by imaging. Potential association between IS and survival was measured using Cox regression analysis, and between IS and pathological outcome with multivariate logistic analysis.Results388 patients underwent surgery. The median IS was 49 days (1–551 days), and was not associated with any of the evaluated outcomes in patients with pancreatic (149) or distal bile duct (46) cancer. For patients with ampullary cancer (71) longer IS was associated with improved survival, with median survival of 27.5 months for patients waiting ≤ median IS (35) and 38.3 months for patients waiting > median IS (36) for surgery (p = 0.041). A higher rate of margin positivity (31.4%) was also noted among patients who waited less than the median IS compared to those waiting longer than this interval (11.4%) (p = 0.032).ConclusionFor patients with ampullary cancer there is a paradoxical improvement in outcome among those with a longer IS, which may be explained by progression to inoperability of more aggressive lesions.     

Outcomes comparing a pancreaticogastrostomy (PG) and a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD)

BackgroundThe advantage of a pancreaticogastrostomy (PG) over a pancreaticojejunostomy (PJ) after a pancreaticoduodenectomy (PD) is not clear.AimThe aim of the present study was to compare the pancreatic fistula (PF, defined according to the International Study Group for Pancreatic Fistula classification) rate and other complications between both methods.MethodsRetrospective analysis of prospectively collected data of 424 [median: 65 years (17–83)] patients who underwent PG (239, 56.4%) and PJ (185, 43.6%) reconstruction between January 2005 and December 2009.ResultsPF occurred in 55 (23.5%) in the PG and 30 (16.2%, P= 0.067) patients in the PJ group. Grade A PF occurred in 19 (7.9%), B in 22 (9.2%) and C in 14 (5.8%) in the PG compared with 5 (2.7%), 12 (6.5%) and in 13 (7.0%), respectively, in the PJ group. The median hospital was 10 days in both groups. The morbidity was higher in the PG group (108, 45.2 vs. 62, 33.5%, P= 0.015). However, there was no significant difference in the 90-day mortality between both groups (PG-17, 7.0% vs. PJ-16, 8.6%, P= 0.558).ConclusionThere was no difference in the overall PF rate, hospital stay and overall mortality between PG and PJ reconstruction methods. However, the grade A PF rate was higher in the PG group.     

Homologous recombination mediates cellular resistance and fraction size sensitivity to radiation therapy

Purpose

Cellular sensitivity to radiotherapy total dose and fraction size is strongly influenced by DNA double strand break (DSB) repair. Here, we investigate response to radiotherapy fraction size using CHO cell lines deficient in specific DNA repair pathways in response to radiation induced DNA double strand breaks (DSB).

Experimental design

We irradiated CHO cell lines, AA8 (WT), irs1SF (XRCC3-), V3-3 (DNA-PKcs-) and EM9 (XRCC1-) with 16 Gy in 1 Gy daily fractions over 3 weeks or 16 Gy in 4 Gy daily fractions over 4 days, and studied clonogenic survival, DNA DSB repair kinetics (RAD51 and 53BP1 foci staining) and cell cycle profiles (flow cytometry).

Results

In response to fractionated radiotherapy, wild-type and DNA repair defective cells accumulated in late S/G2 phase. In cells proficient in homologous recombination (HR), accumulation in S/G2 resulted in reduced sensitivity to fraction size and increased cellular resistance (clonogenic survival). Sensitivity to fraction size was also lost in NHEJ-defective V3-3 cells, which likely rely on functional HR. By contrast, HR-defective irs1SF cells, with functional NHEJ, remained equally sensitive to fractionation throughout the 3-week treatment.

Conclusions

The high fidelity of HR, which is independent of induced DNA damage level, is postulated to explain the low fractionation sensitivity and cellular resistance of cells in S/G2 phase. In conclusion, our results suggest that HR mediates resistance to fractionated radiotherapy, an observation that may help future efforts to improve radiotherapy outcome.     

Activity of Pazopanib and Trabectedin in Advanced Alveolar Soft Part Sarcoma

Background

Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second‐line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi‐institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin.

Materials and Methods

From May 2007, 14 of the 27 centers that were asked to retrospectively review their databases had identified 44 advanced ASPS patients treated with pazopanib and/or trabectedin. Response was evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Progression‐free survival (PFS) and overall survival (OS) were computed by Kaplan‐Meier method.

Results

Among 30 patients who received pazopanib, 18 were pretreated (13 with other antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1 complete response, 7 partial response (PR), 17 stable disease (SD), and 4 progressions. At a 19‐month median follow‐up, median PFS was 13.6 months (range: 1.6–32.2+), with 59% of patients progression‐free at 1 year. Median OS was not reached. Among 23 patients treated with trabectedin, all were pretreated and evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a 27‐month median follow‐up, median PFS was 3.7 months (range: 0.7–109), with 13% of patients progression‐free at 1 year. Median OS was 9.1 months.

Conclusion

The value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas the value of trabectedin appears limited. These results are relevant to defining the best approach to advanced ASPS.

Implications for Practice

This retrospective study, conducted among the world reference centers for treatment of sarcoma, confirms the value of pazopanib in patients with advanced alveolar soft part sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows a limited activity. Alveolar soft part sarcoma is resistant to conventional cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of sarcoma from second line; in the lack of prospective clinical trials, these results are relevant to defining ASPS best management and strongly support initiatives aimed at obtaining the approval of pazopanib in the front line of the disease.     

Socioeconomic status influences the likelihood but not the outcome of liver resection for colorectal liver metastasis

Background

The aim of this study was to compare the socioeconomic profile of patients undergoing liver resection for colorectal liver metastasis (CLM) in a regional hepatopancreatobiliary unit with that of the local population. A further aim was to determine if degree of deprivation is associated with tumour recurrence after resection.

Methods

A retrospective analysis of patients undergoing liver resection for CLM was performed. Geodemographic segmentation was used to divide the population into five categories of socioeconomic status (SES).

Results

During a 7-year period, 303 patients underwent resection for CLM. The proportion of these patients in the two least deprived categories of SES was greater than that of the local population (50.2% versus 40.2%) and the proportion in the two most deprived categories was lower (18.3% versus 30.1%) (P < 0.001). There was no difference in recurrence rate (P = 0.867) or disease-free survival among categories of SES (P = 0.913). Multivariate analysis demonstrated no association between SES and tumour recurrence (P = 0.700).

Conclusions

Liver resection for CLM is performed more commonly among the least socioeconomically deprived population than among the most deprived. However, degree of deprivation was not associated with tumour recurrence after resection.