James A. Gossage

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

PURPOSE Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. METHODS We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. RESULTS Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. CONCLUSION The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

The reporting of needlestick injuries sustained in theatre by surgeons: are we under-reporting?

Surgeons frequently sustain needlestick injuries when operating. The aim of this study was to evaluate the incidence and reporting rate of needlestick injuries at one institution. A questionnaire was distributed anonymously to 69 surgeons of all grades and specialties in a district general hospital in the UK. The questionnaire was returned by 42 surgeons (60.9%). There were 840 needlestick injuries over two years, of which 126 caused bleeding. Senior surgeons who spent more hours operating per week had a higher rate of needlestick injuries compared with junior surgeons (29.1 vs 6.59 injuries per surgeon over two years). Of the total number of injuries, 19 (2.26%) were reported to Occupational Health according to the surgeons questioned, but only six reported incidents were found in the Occupational Health records. Junior surgeons were significantly more likely to report needlestick injuries than senior surgeons (9.82% vs 1.10% of injuries reported, P=0.0000045). The main reasons for failure to report needlestick injuries were due to the lack of time and excessive paperwork. Seventy-three percent of surgeons did not routinely use double gloves when operating, mainly because of decreased hand sensation. The rate of needlestick injury reporting by surgeons at this institution is extremely low. Previous studies have shown a higher reporting rate suggesting that, despite awareness of blood-borne infections, surgeons are still not following recommended protocols.

Adenovirus-Mediated VEGF Gene Therapy Enhances Venous Thrombus Recanalization and Resolution

Objective—Rapid thrombus recanalization reduces the incidence of post–thrombotic complications. This study aimed to discover whether adenovirus-mediated transfection of the vascular endothelial growth factor gene (ad.VEGF) enhanced thrombus recanalization and resolution. Methods and Results—In rats, thrombi were directly injected with either ad.VEGF (n=40) or ad.GFP (n=37). Thrombi in SCID mice (n=12) were injected with human macrophages transfected with ad.VEGF or ad.GFP. Thrombi were analyzed at 1 to 14 days. GFP was found mainly in the vein wall and adventitia by 3 days, but was predominantly found in cells within the body of thrombus by day 7. VEGF levels peaked at 4 days (376±299 pg/mg protein). Ad.VEGF treatment reduced thrombus size by >50% (47.7±5.1 mm2 to 22.0±4.0 mm2, P=0.0003) and increased recanalization by >3-fold (3.9±0.69% to 13.6±4.1%, P=0.024) compared with controls. Ad.VEGF treatment increased macrophage recruitment into the thrombus by more than 50% (P=0.002). Ad.VEGF-transfected macrophages reduced thrombus size by 30% compared with controls (12.3±0.89 mm2 to 8.7±1.4 mm2, P=0.04) and enhanced vein lumen recanalization (3.39±0.34% to 5.07±0.57%, P=0.02). Conclusion—Treatment with ad.VEGF enhanced thrombus recanalization and resolution, probably as a consequence of an increase in macrophage recruitment.

Outcomes following colectomy for Clostridium difficile colitis

INTRODUCTION Clostridium difficile associated diarrhoea has become an important health problem in UK hospitals but surgical intervention is rarely required. There is little evidence regarding best practice for patients requiring surgical intervention. The aim of this multicentre study was to review our experience in patients requiring surgery for C. difficile colitis. METHODS Patients who underwent surgery for C. difficile colitis in 5 hospitals in Southeast England over a 7-year period (1 teaching hospital and 4 district general hospitals) were identified from histopathology databases. Data were collected regarding the presentation, indication for surgery and post-operative outcomes. RESULTS 15 patients (9 males; mean age=71 years (range 35-84 years)) underwent surgery. 46% of patients (n=7) contracted C. difficile during their hospital admission for other medical reasons and 73% of patients were initially admitted under other medical specialties. Diagnosis was only made preoperatively in 8 patients (53%). Indications for surgery were peritonitis and systemic toxicity (n=12), failure of medical management (n=2) and unresolving large bowel dilatation (n=1). 12 patients underwent total colectomy and the rest underwent segmental resection. All patients were admitted to the intensive care unit post operatively with a mean stay of 6 days. 2 patients needed a second look laparotomy. Mortality rate was 67% (n=10), with all but 1 patient dying within the 30-day mortality period. The mean length of hospital stay of survivors was 30 days (range 17-72). CONCLUSIONS Surgical intervention for C. difficile colitis remains uncommon. Total colectomy and end ileostomy is the procedure of choice. The outlook for patients requiring surgery remains poor.

Centralisation of Oesophagogastric Cancer Services: Can Specialist Units Deliver?

INTRODUCTION Oesophagogastric cancer surgery is increasingly being performed in only centralised units. The aim of the study was to examine surgical outcomes and service delivery within a specialist unit. PATIENTS AND METHODS The case notes of all patients undergoing attempted oesophagogastrectomy between January 2000 and May 2003 were identified from a prospective consultant database. RESULTS A total of 187 patients (median age, 63 years; range, 29-83 years; M:F ratio, 3.9:1) underwent attempted oesophago-gastrectomy. Of these, 91% were seen within 2 weeks of referral and treatment was instituted after a mean of 31 days (range, 1-109 days). More patients underwent surgery (63%) than neoadjuvant therapy (56%) within 1 month of referral. The main indication for surgery was invasive malignancy in 166 patients (89%). The 30-day mortality was 0.5% (1 death) and in-hospital mortality was 1.1% (2 deaths). The median length of hospital stay was 14 days (range, 7-69 days). Significant postoperative morbidity included: pulmonary complications (36%), cardiovascular complications (16%), wound infection (13%) and clinically significant anastomotic leaks (7%). Of the study group, 28 patients (15%) were admitted to ICU with a median stay of 10 days (range, 1-44 days); this accounted for 0.9% of ICU bed availability. Twelve patients (6.4%) were returned to theatre, most commonly for bleeding. The 1-year survival rates were 78%. During 2002-2003, national waiting list targets for both hernia repair and cholecystectomy were achieved. CONCLUSIONS Despite recent increases in workload, high volume specialist units can deliver an efficient and timely service with both good treatment outcomes and minimal impact upon elective surgical waiting lists and ICU provision.

Extent of lymphadenectomy and prognosis after esophageal cancer surgery

IMPORTANCE The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. CONCLUSIONS AND RELEVANCE This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.

Prevalence and outcome of litigation claims in England after laparoscopic cholecystectomy

Background:  Approximately, 50,000 cholecystectomies are performed annually in the United Kingdom resulting in a number of negligence claims referred to the NHS Litigation Authority (NHSLA). The aim of this study was to assess the prevalence and outcomes of claims reported to the NHSLA after laparoscopic cholecystectomy performed in England between 1995 and 2008.

Factors associated with early recurrence and death after esophagectomy for cancer.

Accurate selection of patients for radical treatment of esophageal cancer is essential to avoid early recurrence and death (ERD) after surgery. We sought to evaluate a large series of consecutive resections to assess factors that may be associated with this poor outcome.

Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer

The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic (TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO.

Peripheral arterial embolism: prevalence, outcome, and the role of echocardiography in management.

The aims of this study were to review the prevalence and outcome of all surgically treated upper and lower limb emboli presenting to one vascular unit in the last 3 years and to compare transthoracic with transesophageal echocardiography for defining the source of the embolus. All patients who underwent surgical embolectomy for acute limb ischemia from January 2001 to June 2004 were reviewed. Transthoracic and transesophageal echocardiography were carried out on a subset of consecutive unselected patients. Forty-two patients, with a mean age of 80 years, underwent surgical embolectomy from January 2001 to June 2004 (M/F 1:1.8): 27 for lower limb ischemia and 15 for upper limb ischemia. Two thirds of these patients were found to be in atrial fibrillation at presentation (n=28), of whom less than a third were receiving anticoagulants or antiplatelet agents (n=8). The mean hospital stay was 15 days with 36 patients (86%) being fully anticoagulated before discharge from hospital. The 30-day mortality rate was 11% (n=3/27) with 5 patients requiring fasciotomies (12%) and 3 patients requiring an amputation of the lower limb (11%). Postoperatively, 34 patients (81%) had transthoracic echocardiography (TTE), which demonstrated a source or potential source for thrombus in 19 (56%). Fifteen patients (36%) had transesophageal echocardiography (TEE), which changed the subsequent management in 3 patients. All patients in whom TEE altered clinical management would have required this investigation if standard clinical guidelines were followed. TEE did not identify any additional patients with cardiac embolic sources that were not detected by TTE. Arterial limb emboli are still prevalent, but limb salvage and mortality rates appear to be improving. Despite clear guidelines on anticoagulation for patients in atrial fibrillation, many are not receiving appropriate treatment. Transthoracic echocardiography is a good screening tool for detecting a potential cardiac source for peripheral embolism, with transesophageal echocardiography being reserved for specific indications.