Safety and feasibility of preoperative exercise training during neoadjuvant treatment before surgery for adenocarcinoma of the gastro-oesophageal junction.

Background: Neoadjuvant chemotherapy or chemoradiotherapy is used widely before tumour resection in cancer of the gastro-oesophageal junction (GOJ). Strategies to improve treatment tolerability are warranted. This study examined the safety and feasibility of preoperative exercise training during neoadjuvant treatment in these patients. Methods: Patients were allocated to a standard-care control group or an exercise group, who were prescribed standard care plus twice-weekly high-intensity aerobic exercise and resistance training sessions. The primary endpoint was the incidence of serious adverse events (SAEs) that prevented surgery, including death, disease progression or physical deterioration. Preoperative hospital admission, postoperative complications, changes in patient-reported quality of life and pathological treatment response were also recorded. In the exercise group, adherence to exercise and changes in aerobic fitness, muscle strength and body composition were measured. Results: The incidence of SAEs was not increased in the exercise group. The risk of failure to reach surgery was 5 versus 21 per cent in the control group (risk ratio (RR) 0·23, 95 per cent c.i. 0·04 to 1·29), the risk of preoperative hospital admission was 15 versus 38 per cent respectively (RR 0·39, 0·12 to 1·23) and the risk of postoperative complications was 58 versus 57 per cent (RR 1·06, 0·61 to 1·73). The exercise group attended a mean of 17·5 sessions, and improved fitness, muscle strength and Functional Assessment of Cancer Therapy - Esophageal (FACT-E) total score compared with the baseline level. Conclusion: Preoperative exercise training during neoadjuvant treatment in patients with GOJ cancer is safe and feasible, with improvements in fitness, strength and quality of life. Preoperative exercise training may be associated with a lower risk of critical SAEs that preclude surgery or result in hospitalization.

Recurrence following curative intended surgery for an adenocarcinoma in the gastroesophageal junction: a retrospective study.

Recurrence following a resection for an adenocarcinoma of the gastroesophageal junction leads to reduced long-term survival. This study aims to identify risk factors associated with recurrence, recurrence localization, time to recurrence, and long-term survival. All patients undergoing curative intended resection for an adenocarcinoma of the gastroesophageal junction at Rigshospitalet between June 2003 and December 2011 were identified through a prospectively maintained nationwide database and enrolled in this study. Only histologically verified recurrence was considered eligible. Recurrence within six months, microscopically incomplete resection margins, and death within eight weeks were excluded. A total of 348 patients were included in this study. Biopsy-verified recurrence occurred in 120 patients (34.5%), with 32 local (9.2%), and 88 distant (25.3%) recurrences. Lymph node metastases was associated with an increased risk of recurrence (hazard ratio; [95% confidence interval]: HR = 2.7; [1.7-4.3], P < 0.001). Median time to local versus distant recurrence was 18 months (interquartile range (IQR): 9-37 months) versus 17 months (IQR: 11-27 months), P = 0.96, respectively. A trend toward local recurrence was identified if patients had anastomotic leakage (HR = 2.64; [0.89-7.86], P = 0.08). Survival was inversely associated with recurrence, but a survival comparison between local and distant recurrences showed no significant difference: median survival time was 28 months (IQR: 17-43 months) versus 24 months (IQR: 16-36 months), P = 0.45, respectively. A trend toward local recurrence was seen if the patient had an anastomotic leakage event. However, no factors were associated with site-specific recurrence (local vs. distant).

Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction.

BACKGROUND AND AIMS: Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy. METHODS: From 2003 to 2009, 211 patients underwent curative resection. Surgery alone was performed in 95 pa-tients and 116 patients received adjuvant therapy after resection. All patients underwent Lewis-Tanner operation with D1 node resection including coliac nodes (D1+). Informations about recurrence and death were collected from the Danish Cancer Register and the Central Death Register. Patients who died after experiencing severe complications after surgery were excluded from the survival analysis. Patients with T0N0 or T1N0 were also excluded because patients of this category were not given adjuvant therapy according to the Macdonald protocol. RESULTS: Patients with positive node status in the resected specimen, the 3-year disease-free survival after adjuvant chemoradiotherapy (n = 91) or surgery alone (n = 43) was 24% and 37%, respectively. Median time of survival was prolonged by 10 month in favour of those who received chemoradiotherapy. However, after controlling for the confounding effect of age and node status, only positive node status in the resected specimen had significant partial effect on survival. CONCLUSION: Chemoradiotherapy according to the Intergroup-0116 protocol might still be a reasonable option after curative resection in patients with GEJ adenocarcinomas and positive lymph node status, who did not receive neoadjuvant chemotherapy.

Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study.

AIMS: Whether the association between fibrinogen and cardiovascular events reflects an association with advanced atherosclerosis in general, or rupture-prone plaques in particular, is unclear. We examined whether fibrinogen predicts incidence of ischaemic stroke, advanced atherosclerosis (measured as carotid artery stenosis) and/or echolucent, rupture-prone plaques. METHODS AND RESULTS: Study 1-8755 Copenhagen City Heart Study stroke-free participants; we observed 235 ischaemic strokes during 6 years of follow-up. Study 2-318 carotid stenosis patients and 1584 age- and gender-matched controls. Study 3-159 patients with echolucent vs 159 patients with echo-rich carotid artery plaques. Fibrinogen above vs below the median value of 3 g l(-1)predicted risk of ischaemic stroke (relative risk: 1.9; 95% CI: 1.4-2.5; 235 events). Significant risk was found in men (2.7; 1.7-4.2; 113 events) and with a similar trend in women (1.4; 0.9-2.0; 122 events), in young (5.2; 1.1-26; eight events) and middle aged (2.9; 1.6-5.4; 64 events) with a similar trend in the elderly (1.4; 1.0-2.0; 163 events). Fibrinogen levels in those with and without ischaemic stroke were 3.6 and 3.1 g l(-1)(ANCOVA: P<0.0001). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1 g l(-1)(P<0.0001); equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4 mg l(-1)(P<0.0001). Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (P=0.61 and P=0.28); the power to exclude a 15% increase in fibrinogen or a 50% increase in high-sensitive C-reactive protein was 98 and 54%, respectively. CONCLUSIONS: Elevated fibrinogen predicts future ischaemic strokes, particularly in men and in the young and middle aged. This is most likely a reflection of advanced atherosclerosis, rather than an association with rupture-prone plaques.

Real-time spatial compound imaging improves reproducibility in the evaluation of atherosclerotic carotid plaques.

Compound imaging has the ability of reducing speckle and clutter artifacts demonstrated in in vitro studies compared to conventional, single-angle imaging. We investigated intra- and interobserver agreement of 38 outlines of carotid artery plaque images acquired by these techniques, by measuring the overlapping area after repeated outlines. In general, both techniques showed good agreement. When considering the images with poorest overlap, compound imaging had a significant advantage over conventional imaging regarding both intra- and interobserver agreement. The interobserver variation for the overlapping area after two outlines was 20% for conventional technique and 10% for compound. The interobserver variation of the gray scale median value (GSM) for conventional technique ranged from -32 to +20 and from -6 to +6 for compound. Likewise, the coefficient of repeatability for the GSM value was 13 for conventional imaging and three for compound imaging, and interobserver variation for the GSM value for the overlapping area was 34% and 9% for conventional and compound technique. In conclusion, compound imaging improves intra- and interobserver agreement and reduces interobserver variation in the GSM value in a clinical setting.

Angioplasty for the treatment of buttock claudication caused by internal iliac artery stenoses.

A case of buttock claudication due to isolated internal iliac artery stenoses is presented. Although ankle systolic pressure at rest was within normal limits and distal pulses were palpable, an angiogram demonstrated severe stenoses. A computed tomography scan showed no spinal stenosis. The patient was successfully treated with angioplasty. This diagnosis may be elusive if ankle pressure or distal pulses are normal, thereby directing the clinician's suspicion away from vascular pathology.

[Lipid lowering treatment of patients with atherosclerotic disease of the lower extremities]. / Lipidsaenkende behandling af patienter med aterosklerotisk sygdom i underekstremiteterne.

Patients with critical peripheral ischaemia have a significant mortality rate of up to 50% within 4-5 years of surgical vascular reconstruction. This poor survival rate is due to concomitant coronary and cerebrovascular atherosclerotic disease. Large randomised trials have shown that dyslipidaemia is easily modifiable in patients both with and without established coronary artery disease, with significant reductions in cardiovascular morbidity and mortality. Although none of these trials directly measured peripheral vascular status, there is every indication that conclusions submitted for patients with ischaemic heart disease can be translated to patients with peripheral arterial disease (PAD). The object of this review was therefore to divulge the current evidence available, which supports active treatment of dyslipidaemia in patients with PAD.

[Follow-up after infraligamental PTA treatment]. / Followup efter infraligamentaer PTA-behandling.

A total of 48 percutaneous transluminal angioplasties (PTAs) of the superficial femoral and popliteal artery performed between 1993 and 1998 were evaluated with ultrasound duplex scanning and ankle-arm pressure. Twenty-seven (60%) patients presented with claudication and 18 (40%) had limb-threatening ischaemia. Three patients had bilateral PTA. The PTAs were initially successful, corresponding to an early patency rate of 87.5% within the first four weeks. The 12 month patency rate, calculated by life table method, was 68% and 72%, respectively (non-significant). The mortality was 4% and 33% respectively during the first year (p < 0.05). In spite of the size of the material, PTA of the femoropopliteal arterial segment is considered as a valid alternative treatment to vascular surgery in patients presenting with claudication and in patients presenting limb-threatening ischemia.

[Variation of Doppler ultrasonography of carotid arteries]. / Variationen af UL-Doppler undersøgelse af a. carotis.

The variation of ultrasound examination of the carotid arteries performed at two different hospitals was examined by retrospective analysis. Eighty-one patients were primarily examined by ultrasound at their local hospital on the suspicion of carotid stenosis. Following referral, they underwent a further scanning at the Dept. of Vascular Surgery, Rigshospitalet. Results for 143 carotid arteries were available for comparison. The overall agreement between the two examinations was only 59%. In nine of 40 (22%) cases an originally diagnosed minor stenosis was found to be significant and 3/19 (16%) with shown occlusion were found to be patent at the later examination. In order to draw clinical conclusions validation of each individual laboratory performing ultrasound examination of extracranial cervical arteries is necessary.

A closed rebreathing system for dose maintenance during Partial Liquid Ventilation.

Partial Liquid Ventilation (PLV), a treatment for acute respiratory failure in which the lungs are filled, either partially or to functional residual capacity (FRC), with perfluorochemical (PFC) liquid while the patient is on mechanical gas ventilation, has progressed to clinical trials using the PFC perflubron (PFB). Because gas expired during PLV is laden with PFB vapor, PFB is lost via evaporation, which increases dose consumption and necessitates periodic redosing. A device has been developed to minimize evaporative loss by confining PFC vapor to a gas volume breathed by the patient, which is isolated from the ventilator. This closed rebreathing system works with the ventilator such that after the lung is filled with PFB, the patient is connected to the rebreathing system, with breathing still "driven" by the ventilator. The rebreathing system consists of two gas circuits, or compartments, separated by a flexible bag (in a box) partition. One compartment is in gas communication with the lung, while the second communicates with the ventilator. The O2 level on the patient side is matched to that on the ventilator side by sensing gas concentrations and by feedback control of O2 introduction. Similarly, air is introduced into the patient side under pressure-based feedback control to maintain a constant gas volume. On inspiration, the ventilator delivers the tidal volume (breath) into the box surrounding the bag, which, in turn, is transmitted through the bag to the lung. On expiration, the process is reversed. Unidirectional circulation of gas in the rebreathing circuit is achieved via check valves, and expired CO2 is removed by a barium hydroxide lime cartridge. Airway humidification is maintained by captive water vapor in the system and water vapor from the CO2 absorber. It is recommended that flow, pressure, O2, and CO2 levels be monitored at the patient "Y," i.e., the proximal end of the endotracheal tube. Performance data from both in-vitro experiments and in-vivo PLV experiments in pigs are presented. The authors conclude that with the closed rebreathing system, the dose can be safely maintained with fewer redosing procedures, and an approximately 90% savings in dose is achieved.

[Causes of need for reoperation following surgery for varicose veins in Denmark]. / Arsager til behov for genbehandling efter variceoperationer i Danmark.

In a surgical varicose vein practice 509 patients who had suffered recurrent varicose veins following surgery in other institutions were traced. The causes of recurrences were identified in a retrospective analysis and related to the source of primary treatment: in hospital treatment (n = 290), surgical practice (n = 56) or another varicose vein specialist (n = 104). A significant difference was noted between the three institutions in the use of saphenofemoral resection (78%, 63% and 97%) as well as greater saphenous vein stripping (44%, 14% and 0%). Lack of or insufficiently performed saphenofemoral surgery were identified as contributing to saphenofemoral insufficiency in 40% and 43% of patients primarily treated in hospital and in surgical practice, respectively, but only in 14% of those treated by a varicose vein specialist (p < 0.001). Primary sapheno-popliteal resection had been used equally infrequently (11%, 13% and 16%, respectively) and was equally frequently insufficiently performed (66%, 57% and 41%). This retrospective investigation concludes that insufficient varicose vein surgery is a major contributor to recurrences, particularly when primary surgery is performed in hospital or in surgical practice, as opposed to in a varicose vein practice. These results warrant a reorganisation of varicose vein surgery in Denmark.

CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease.

Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients. In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression of epithelial nuclear proliferation antigen, and elongation of the crypts. Later on, massive mononuclear cell infiltration, hypertrophy of all layers of the colon and occasional epithelial ulcerations were observed. At this stage, accumulations of IgA, IgM and small numbers of IgG1-, IgG2- and IgG3-secreting plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages, neutrophils and plasma cells secreting IgA, IgM, and to a lesser degree IgG antibodies which might play an accessory role in the pathogenesis of IBD.