This 5-year evaluation provides strong evidence that the classification is valid and applicable worldwide in many fields of surgery. No modification in the general principle of classification is warranted in view of the use in ongoing publications and trials. Subjective, inaccurate, or confusing terms such as "minor or major" should be removed from the surgical literature.

The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction–based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.

This single institution, high-volume experience indicates that pancreaticoduodenectomy can be performed safely for a variety of malignant and benign disorders of the pancreas and periampullary region. Overall survival is determined largely by the pathology within the resection specimen.

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Results Participants were allocated to vitamin D 3 vs. placebo in equal numbers; 82% were vitamin D insufficient at baseline. Vitamin D 3 supplementation did not influence time to first severe exacerbation (aHR 1.02, 95% CI 0.69-1.53, P = 0.91) or time to first URI (aHR 0.87, 95% CI 0.64-1.16, P = 0.34). The influence of vitamin D 3 on co-primary outcomes was not modified by baseline vitamin D status or genotype. Of 16 pre-specified secondary outcomes, only one showed a difference between arms: vitamin D supplementation induced a modest improvement in respiratory quality of life as evidenced by a reduction in mean total score for the St George's Respiratory Questionnaire at 2 months (-3.9 points, p = 0.005), 6 months (-3.7 points, p = 0.038) and 12 months (-3.3 points, p = 0.060). Conclusions Vitamin D 3 supplementation did not influence time to exacerbation or URI in a population of adults with ICS-treated asthma with a high prevalence of baseline vitamin D insufficiency. Introduction Severe Asthma, characterised by persistent symptoms despite maximal medical therapy, represents 5% of asthma cases. Bronchial Thermoplasty (BT) is a novel therapy, NICE approved for Severe Asthma patients uncontrolled despite step 4/5 of British Guideline on Asthma Management. BT delivers radiofrequency thermal energy to airways distal to the main-stem bronchi, permanently reducing airway smooth muscle mass. It is unknown whether treatment of smooth muscle hypertrophy impacts persistently upon systemic signs of allergic inflammation. Peripheral blood eosinophils (PBEs) are a marker of allergic inflammation in asthma. We asked: does BT modify signs of allergic inflammation as measured by PBEs and if so, does this effect persist over time? Method A retrospective review of 15 consecutive Severe Asthma cases treated with BT was performed. Serial PBEs measured before and up to 1 year after BT were compared. Blood eosino-phil levels taken peri-procedure were excluded from analysis due to standard protocol concomitant steroid therapy. For time to first detectable high PBE all available post-BT PBE levels were assessed. Results 13 patients had PBE data before and after BT, with an average of 9 and 12 serial PBE levels pre and post-BT respectively. Mean PBE 1 year pre-BT was 0.33 Â 10 9 /L falling to a mean of 0.16 Â 10 9 /L 1 year post-BT (p < 0.05) (see Figure). 9 of 13 patients had a fall in mean PBE, in 2 of 13 levels rouse and 1 of 13 mean PBEs were unchanged post-BT. In 6 patients who converted from normal to high PBE post-BT, average time to first high PBE (>0.4 Â 10 9 /L) was 7 months (range 1-13 months). In 5 patients (38%) PBE remained within normal range persistently post BT. Conclusion Severe Asthma patients undergoing BT had a significant reduction in average peripheral blood eosinophil levels from baseline. In over 1/3 of cases this effect was persistent 1 year post procedure. These findings support the concept that BT not only reduces asthma-associated smooth muscle hypertrophy but impacts upon systemic markers of allergic i...

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ObjectiveTo examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. Summary Background DataHepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. MethodsData from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. ResultsThe median survival for the entire cohort was 46 months, with 5-and 10-year survival rates of 40% and 26% respectively.Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993)(1994)(1995)(1996)(1997)(1998)(1999). Both overall and diseasefree survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors Յ 3, negative resection margin, and CEA Ͻ 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. ConclusionsLong-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.Hepatic resection has gained acceptance as the most effective therapy for patients with colorectal metastases confined to the liver. Advances in surgical planning, operative technique, and perioperative care have resulted in improved short-term outcomes, with experienced centers now reporting in-hospital mortality rates of less than 5%, even with major resections. 1-5Long-term survival and potential for cure following surgical resection for hepatic colorectal metastases have been demonstrated in numerous uncontrolled studies. In most series, the overall 5-year survival rate reported following hepatic resection with curative intent ranges from 25%-37%, and with median survival of between 24 and 40 months.1-3,6 -10 As hepatic resections have become safer and indications have broadened, there are increasing expectations regarding assessment of trends in long-term patient outcomes. Although some improvement in survival are being reported in more recent series compared with th...

Pancreaticoduodenectomy has become a commonly performed operation in many tertiary care centers. Operative time, blood loss, and length of stay have dropped substantially. The operation has become safe, with a low hospital mortality. It has become an effective operation for pancreatic cancer in those patients in whom their tumor is margin negative and node negative.