Does a high Mandard score really define a poor response to chemotherapy in oesophageal adenocarcinoma?

Background A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients.Methods Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.Results Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1–3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16–0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (−16.3 vs −7.7 cm³, p = 0.033) with no significant difference between Mandard groups.Conclusion Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.Subject terms: Oesophageal cancer, Surgical oncology     

The use of cadaver models to diagnose rib fractures: A pilot study

Background

In the emergency department, rib fractures are a common finding in patients who sustain chest trauma. Rib fractures may be a sign of significant, underlying pathology, especially in the elderly patients where rib fractures are associated with significant morbidity and mortality. To date, no studies have evaluated the ability of ultrasound to detect rib fractures using cadaver models and subsequently use this model as a teaching tool.

Morphologic and functional changes in nontumorous liver tissue after radiofrequency ablation in an in vivo model: comparison of 18F-FDG PET/CT, MRI, ultrasound, and CT.

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on (18)F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and (18)F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. METHODS: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities-MRI, CT, and ultrasound-and by (18)F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. RESULTS: Immediately after radiofrequency ablation, no increase in (18)F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in (18)F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. CONCLUSION: If performed immediately after radiofrequency ablation, (18)F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.     

Analysis of LPS released from Salmonella abortus equi in human serum.

We investigated in which form lipopolysaccharide (LPS) is released from live bacteria incubated with human serum and whether the released LPS can interact with high density lipoprotein (HDL), the main transport protein for purified LPS in circulation. Live biotinylated Salmonella abortus equi bacteria were incubated with fresh serum (37 degrees C; 2 h). The released LPS was isolated by immunoprecipitation or immunoabsorption using specific anti-O antibodies. It was analysed and compared with purified LPS, also incubated with serum under identical conditions. Immunoprecipitation led to a 35% recovery and immunoabsorption to quantitative recovery of released or purified LPS. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and subsequent immunoblot analysis revealed that all molecular species present in the purified LPS were present in the released LPS. The rough fraction, which was co-isolated from serum together with the true smooth (O-polysaccharide-containing) molecules, exhibited S. minnesota rough mutant Rb antigenic specificity. In the immunoprecipitated material two forms of released LPS were identified. One represented LPS associated with a biotinylated bacterial component with an apparent molecular mass of 35-36 kDa, which was identified as OmpA, a major outer membrane protein. The OmpA-associated LPS was free of HDL. Another part of the released LPS was free of biotinylated bacterial components. This portion of LPS was associated with HDL, indicating that the interaction with HDL may also proceed with a part of LPS released from bacteria.     

Constipation in the population over 50 years of age in Albacete province.

OBJECTIVE: To Determine the incidence of constipation in Albacete province and its relation with diet and lifestyle. PATIENTS AND METHODS: Cross-sectional population survey. We studied 414 participants over 50 years of age in Albacete province. 445 persons over 50 years of age were included in the study. All participants were selected by systematic random sampling; 414 participants filled in the questionnaire correctly. Main measures: age, weight and height, marital status, level of education and occupation; presence of a disease, number of sleep hours a day, physical exercise, smoking, alcohol intake, drug intake (anti-inflammatories and laxatives); bowel habit, diet, meal frequency and place; food intake frequency per week, daily intake of water, coffee, tea and herbal beverages; vitamin and fiber supplements; presence of cancer in the family. RESULTS: 56.9% of participants were women. Mean age 67.07 years. In Albacete province, 4.4% of the population over 50 years have a bowel habit consistent with constipation. Most participants had three meals a day (breakfast, lunch, and supper), while 50% had another meal in the morning or afternoon. These meals took place, habitually, in the domicile. There was a preponderance in daily intake of the following foods: milk (83.7%), bread (95.1%), vegetables (68.8%), fruit (91.8%), and virgin olive oil (96.6%). Fish was eaten every one to two days, and pulses and meat every three to six days. 44.4% of participants drank one to two liters of water a day. Only 3.9% of participants took some supplement; 35% of participants were on a diet. It was observed that 97.7% of participants with more than three defecations a week had a high intake of virgin olive oil; 65.7% of participants did some physical exercise customarily; 70.2% of participants were non-smokers, 10.2% were smokers, and 18.4% were ex-smokers. With regard to alcohol, the percentage of drinkers was 35.1%. The main class of medications taken by participants was NSAIDs - 14.5%; 79.7% took neither NSAIDs nor laxatives. Only 2.7% of participants took laxatives regularly. CONCLUSIONS: Most participants had relatively healthy eating habits.     

Colchicine prevents tumor necrosis factor-induced toxicity in vivo.

Tumor necrosis factor (TNF) toxicity was induced in vivo by intravenous administration of 15 micrograms of recombinant murine TNF-alpha per kg to galactosamine-sensitized mice. Within 8 h, the animals developed a fulminant hepatitis. Intravenous administration of 0.5 mg of colchicine per kg at 19 and 4 h prior to TNF challenge protected the animals against hepatitis. Lipopolysaccharide (LPS)-stimulated, bone marrow-derived macrophages from C3H/HeN mice released significant amounts of TNF in vitro. When such macrophages were intravenously given to LPS-resistant galactosamine-sensitized C3H/HeJ mice, these animals died within 24 h. Preincubation of these transferred macrophages with colchicine did not suppress the LPS-inducible TNF release from these cells. Concordantly, administration of macrophages exposed to colchicine in vitro resulted in full lethality. However, in vivo pretreatment of C3H/HeJ mice with colchicine 19 and 4 h prior to the transfer of LPS-stimulated macrophages prevented lethality. In LPS-responsive NMRI mice which had been protected against galactosamine-LPS-induced hepatitis by pretreatment with colchicine, TNF was still released into the blood. We conclude from our findings that the in vivo protection by colchicine is mediated by blocking TNF action on target cells while the effector cells of LPS toxicity, i.e., the macrophages, remain responsive.