Burden of in-hospital care in oesophageal cancer: national population-based study.

BACKGROUND: Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for patients with oesophageal cancer in relation to intended treatment, and to analyse factors associated with risk of spending a large proportion of survival time in hospital. METHODS: All patients with oesophageal cancer in three nationwide registers over a 10-year period were included. In-hospital care during the first year after diagnosis was evaluated, and the proportion of survival time spent in hospital, stratified by intended treatment (curative, palliative or best supportive care), was calculated. Associations between relevant factors and a greater proportion of survival time in hospital were analysed by multivariable logistic regression. RESULTS: In-hospital care was provided for a median of 39, 26, and 15 days in the first year after diagnosis of oesophageal cancer in curative, palliative, and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12 per cent of their survival time in hospital during the first year after diagnosis, whereas those receiving palliative or best supportive care spent 19 and 23 per cent respectively. Factors associated with more in-hospital care included older age, female sex, being unmarried, and chronic obstructive pulmonary disease. CONCLUSION: The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.

Outcome of microscopically non-radical oesophagectomy for oesophageal and oesophagogastric junctional cancer: nationwide cohort study.

BACKGROUND: Microscopically non-radical (R1) oesophageal cancer resection has been associated with worse survival. The aim of this study was to identify risk factors for R1 resection and to investigate how this affects long-term survival. METHODS: The Swedish National Register for Oesophageal and Gastric Cancer was used to identify all patients who underwent oesophageal cancer resection with curative intent between 2006 and 2017. Risk factors for R1 resection were assessed by multivariable logistic regression analysis, and factors predicting 5-year survival identified by multivariable Cox regression. RESULTS: The study included 1460 patients. Surgical margins were involved microscopically in 142 patients (9.7 per cent). The circumferential resection margin was involved in 114 (7.8 per cent), the proximal margin in 53 (3.6 per cent), and the distal margin in 29 (2.0 per cent). In 30 specimens (2.1 per cent), two or all three margins were involved. Independent risk factors for R1 resection were male sex, low BMI, absence of neoadjuvant treatments, and clinical T4 disease. The 5-year survival rate for the entire cohort was 42.2 per cent, but only 18.0 per cent for those who had an R1 resection. Independent risk factors for death within 5 years of resection were male sex, age above 60 years, normal BMI, ASA fitness grade III, intermediate-level education, R1 resection (hazard ratio 1.80, 95 per cent c.i. 1.40 to 2.32), clinical T3 disease, and clinical lymph node metastasis. CONCLUSION: R1 resection is common and predicts poor 5-year survival. Absence of neoadjuvant treatment is a risk factor for R1 resection.

Complications and survival after hybrid and fully minimally invasive oesophagectomy.

BACKGROUND: Minimally invasive oesophagectomy (MIO) is reported to produce fewer respiratory complications than open oesophagectomy. This study assessed differences in postoperative complications between MIO and hybrid MIO (HMIO) employing thoracoscopy and laparotomy, along with the influence of co-morbidities on postoperative outcomes. METHODS: Patients with oesophageal cancer undergoing three-stage MIO or three-stage HMIO between 1999 and 2018 were identified from a prospectively developed database, which included patient demographics, co-morbidities, preoperative therapies, and cancer stage. The primary outcome was postoperative complications in the two groups. Secondary outcomes included duration of operation, blood transfusion requirement, duration of hospital stay, and overall survival. RESULTS: There were 828 patients, of whom 722 had HMIO and 106 MIO, without significant baseline differences. Median duration of operation was longer for MIO (325 versus 289 min; P < 0.001), but with less blood loss (median 250 versus 300 ml; P < 0.001) and a shorter hospital stay (median 12 versus 13 days; P = 0.006). Respiratory complications were not associated with operative approach (31.1 versus 35.2 per cent for MIO and HMIO respectively; P = 0.426). Anastomotic leak rates (10.4 versus 10.2 per cent) and 90-day mortality (1.0 versus 1.7 per cent) did not differ. Cardiac co-morbidity was associated with more medical and surgical complications. Overall survival was associated with AJCC stage and co-morbidities, but not operative approach. CONCLUSION: MIO had a small benefit in terms of blood loss and hospital stay, but not in operating time. Oncological outcomes were similar in the two groups. Postoperative complications were associated with pre-existing cardiorespiratory co-morbidities rather than operative approach.

Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women.

Cardiometabolic diseases are primarily linked to enlarged visceral adipose tissue (VAT). However, some data suggest heterogeneity within the subcutaneous adipose tissue (SAT) depot with potential metabolic differences between the superficial SAT (sSAT) and deep SAT (dSAT) compartments. We aimed to investigate the heterogeneity of these three depots with regard to fatty acid (FA) composition and gene expression. Adipose tissue biopsies were collected from 75 obese women undergoing laparoscopic gastric bypass surgery. FA composition and gene expression were determined with gas chromatography and quantitative real-time-PCR, respectively. Stearoyl CoA desaturase-1 (SCD-1) activity was estimated by product-to-precursor FA ratios. All polyunsaturated FAs (PUFA) with 20 carbons were consistently lower in VAT than either SAT depots, whereas essential PUFA (linoleic acid, 18:2n-6 and α-linolenic acid, 18:3n-3) were similar between all three depots. Lauric and palmitic acid were higher and lower in VAT, respectively. The SCD-1 product palmitoleic acid as well as estimated SCD-1 activity was higher in VAT than SAT. Overall, there was a distinct association pattern between lipid metabolizing genes and individual FAs in VAT. In conclusion, SAT and VAT are two distinct depots with regard to FA composition and expression of key lipogenic genes. However, the small differences between sSAT and dSAT suggest that FA metabolism of SAT is rather homogenous.

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m-2 ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day-1 ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m-2 ) served as controls. RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Laparoscopy in Duodenal Switch: Safe and Halves Length of Stay in a Nationwide Cohort from the Scandinavian Obesity Registry.

BACKGROUND AND AIMS: Unsatisfactory weight loss after gastric bypass or sleeve gastrectomy in super-obese patients (body mass index > 50) is a growing concern. Biliopancreatic diversion with duodenal switch results in greater weight loss, but is technically challenging to perform, especially as a laparoscopic procedure (Lap-DS). The aim of this study was to compare perioperative outcomes of Lap-DS and the corresponding open procedure (O-DS) in Sweden. MATERIAL AND METHODS: The data source was a nationwide cohort from the Scandinavian Obesity Surgery Registry and 317 biliopancreatic diversion with duodenal switch patients (mean body mass index = 56.7 ± 6.6 kg/m2, 38.4 ± 10.2 years, and 57% females) were analyzed. Follow-up at 30 days was complete in 98% of patients. RESULTS: The 53 Lap-DS patients were younger than the 264 patients undergoing O-DS (35.0 vs 39.1 years, p = 0.01). Operative time was 163 ± 38 min for lap-DS and 150 ± 31 min for O-DS, p = 0.01, with less bleeding in Lap-DS (94 vs 216 mL, p < 0.001). There was one conversion to open surgery. Patients undergoing Lap-DS had a shorter length of stay than O-DS, 3.3 versus 6.6 days, p = 0.02. No significant differences in overall complications within 30 days were seen (12% and 17%, respectively). Interestingly, the two leaks in Lap-DS were located at the entero-enteric anastomosis, while three out of four leaks in O-DS occurred at the top of the gastric tube. CONCLUSION: Lap-DS can be performed by dedicated bariatric surgeons as a single-stage procedure. The use of laparoscopic approach halved the length of stay, without increasing the risk for complications significantly. Any difference in long-term weight result is pending.

Adenovirus vector designed for expression of toxic proteins.

To construct recombinant adenoviruses expressing biologically active proteins may be impossible, or result in a significant reduction in virus yield, if the protein expressed has an inhibitory effect on virus replication or cellular growth. To overcome this problem, we previously designed adenovirus vectors expressing foreign proteins from inducible promoters. However, during our work with a replication-deficient virus expressing the ASF/SF2 splicing factor from a progesterone antagonist-inducible gene cassette, we discovered that ASF/SF2 was expressed at a significant level in the 293 producer cell line, even in the absence of inducer. 293 cells code for adenovirus E1A and E1B proteins and thus support the growth of E1-deficient adenoviruses. Here we show that this background ASF/SF2 expression results from a low level of E1A-mediated transactivation of the basal promoter driving transgene expression. To overcome the problem of leaky expression, we reconstructed a novel gene cassette that combines an inducible promoter and a Lac repressor protein-based block to reduce transcriptional elongation. We show that this novel vector system dramatically reduced background transgene expression and therefore should be useful for the rescue and propagation of high-titer stocks of recombinant adenoviruses expressing toxic proteins.