Completeness and registration bias in PROCARE, a Belgian multidisciplinary project on cancer of the rectum with participation on a voluntary basis.

BACKGROUND: PROCARE, a Belgian multidisciplinary project on rectal cancer, started in 2006 with participation on a voluntary basis. Completeness and bias of registration in PROCARE were assessed. METHODS: Data from 6353 patients with rectal cancer were extracted from the population based Belgian Cancer Registry for the period 2006-2008. Registration bias was studied by comparing patient, tumour and treatment characteristics of cases registered and non-registered in PROCARE. Relative survival (RS) of patient subgroups was analysed. RESULTS: PROCARE included 37% of all Belgian rectal cancer patients. Registration was highly variable between participating centres which recorded on average 56% of their patients. Significant differences in patient, tumour and treatment related characteristics were observed between registered and non-registered patients. The 5-year RS was 77% (95% confidence interval (CI): 74-80%) for registered patients and 56% (95% CI: 53-59%) for non-registered patients. After adjustment for patient, tumour characteristics and volume of centre, the relative excess risk of dying (RER) between registered and non-registered patients was 2.15 (95% CI: 1.85-2.50, p<0.001). The 5-year RS of patients treated in centres that never participated in the project was 59% (95% CI: 55-63%) and, after adjustment, the RER was 1.16 (95% CI: 1.00-1.35, p<0.050) compared to patients of the participating centres. CONCLUSION: Registration of PROCARE patient data was incomplete, biased and variable between centres. Participation on a voluntary basis should be avoided for further projects. Quality assurance on a centre level requires compulsory and complete registration with a minimal but relevant data set for all patients treated in all centres.

Outcome following laparoscopic and open total mesorectal excision for rectal cancer.

BACKGROUND: There are few reports on the oncological quality of resection and outcome after laparoscopic versus open total mesorectal excision (TME) for rectal cancer in everyday surgical practice. METHODS: Between January 2006 and October 2011, data for patients with mid or low rectal adenocarcinoma who underwent elective TME were recorded in the PROCARE database. A multivariable model and the propensity score as a co-variable in Cox or logistic regression models were used for adjustment of differences in patient mix and non-random assignment of surgical approach. RESULTS: Data for 2660 patients from 82 hospitals were recorded. Implementation of laparoscopic TME was highly variable. The oncological quality of resection was similar in the laparoscopic and the open group: incomplete mesorectal excision in 13·2 and 11·4 per cent respectively, circumferential resection margin positivity in 18·1 per cent, and a median of 11 lymph nodes examined per specimen in both groups. The hazard ratio for survival after laparoscopic versus open TME was 1·05 (95 per cent confidence interval 0·88 to 1·24) after correction for differences in patient mix, and 1·06 (0·89 to 1·25) after correction for the propensity score. The definitive colostomy rate was similar in the two groups: 31·0 per cent after open and 31·4 per cent after laparoscopic TME. Postoperative morbidity was lower and length of stay was shorter after laparoscopic TME compared with open TME. Survival was not negatively affected by converted laparoscopic resection, whereas postoperative morbidity, mortality and length of stay after converted laparoscopy were comparable with those after open TME. CONCLUSION: Oncological outcome is comparable after laparoscopic and open TME in everyday surgical practice.

Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre.

BACKGROUND: Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia-reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. METHODS: This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. RESULTS: Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. CONCLUSION: IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. REGISTRATION NUMBER: NCT00908245 (http://www.clinicaltrials.gov).

Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

Surgical management of a combined fracture of the odontoid process with an atlas posterior arch disruption: a review of four cases.

Four cases of operated odontoid process fractures associated with a fracture of the posterior arch of the atlas are presented. Three types of surgery were performed: atlas-axis fusion, occipitocervical fusion, and odontoid process screw fixation. Based on a literature review and our experience, the therapeutic management is discussed according to the type of odontoid fracture and the presence of neurological involvement, with a reminder that wiring is not indicated when C1 posterior arch continuity is compromised.

Fetal calf serum-primed dendritic cells induce a strong anti-fetal calf serum immune response and diabetes protection in the non-obese diabetic mouse.

In recent years, several investigators have shown that transfer of dendritic cells (DC) prevents diabetes development in non-obese diabetic (NOD) mice. Accumulating evidences showing that DC cultured in medium containing fetal calf serum (FCS) can induce a dominant unspecific immune response in tumor models after i.v. injection prompted us to investigate if the protecting effect of DC on diabetes development in NOD mice might be supported by the induction of an anti-FCS immune response in recipient mice. Five-week-old NOD mice were injected i.v. with FCS-cultured bone marrow-derived DC or PBS as control. Levels of anti-FCS and anti-bovine serum albumin (BSA) antibodies were measured in the serum of recipient mice. Anti-FCS cellular immune responses were also analysed after a single DC injection using in vitro proliferation of splenocytes either in RPMI supplemented with FCS, AIMV-BSA or RPMI containing autologous mouse serum or BSA as a read out. DC injection prevented diabetes development in NOD mice and high titers of anti-FCS and anti-BSA antibodies were detected in serum of all DC-injected mice. Besides, splenocytes isolated from DC-injected mice proliferated vigorously in the presence of bovine proteins in contrast to splenocytes isolated from control mice but removing bovine proteins abrogated the high level of proliferation of those splenocytes suggesting that lymphocytes have been primed against bovine proteins in vivo after DC injection. All together, our data show that DC transfer induced cellular and humoral anti-FCS immune responses in recipient NOD mice suggesting that the protective effect of DC relies on their unspecific immunostimulatory effects.

Microchimerism and transmission of porcine endogenous retrovirus from a pig cell line or specific pathogen-free pig islets to mouse tissues and human cells during xenografts in nude mice.

AIMS/HYPOTHESIS: Pig islets could transmit porcine endogenous retroviruses (PERV) to diabetic patients. Our previous work showed that pig islets expressed low levels of PERV mRNA and were not likely to transmit PERV to human cells in vitro. The real risk of infection during pig tissue xenografts can only be evaluated by in vivo experiments. METHODS: Nude mice bearing tumours containing human 293 cells were grafted with specific pathogen-free pig islets or PERV-producing pig PK15 cells to determine whether pig cells could transmit PERV to mouse and human cells in vivo. Infection was monitored by PCR, long PCR, RT-PCR and long RT-PCR. As detection of PERV sequences could be due to the presence of residual pig cells, we looked for pig mitochondrial (mt) DNA. Quantitative PCR for PERV and pig mt DNA was done to compare the PERV-to-pig mt (P-to-M) ratio of each sample with the reference ratio for grafted pig cells. RESULTS: Among 78 mouse tissues from PK15-grafted mice, 54 and 72 were positive for gag and pig mt DNA, respectively. Human tumours developed in these mice were positive for PERV (78%) and pig mt (89%). The P-to-M ratios for mouse tissues and PERV-positive human tumours from PK15-grafted mice were higher than the ratio in PK15 cells. Among 41 tissues from pig islet cell-grafted mice, 7 were positive for PERV (3 lymph nodes, 1 kidney, 2 salivary glands, 1 ovary), and 14 were positive for pig mt DNA. Three of these samples (1 lymph node, 1 kidney and 1 salivary gland) were positive for gag DNA, but negative for pig mt DNA. One human tumour in these mice was positive for PERV DNA. P-to-M reference ratio in grafted islet cells was 0.05+/-0.03. The three PERV-positive lymph nodes contained 78 gag/3 mt copies (P-to-M: 26), 101 gag/3 mt copies (P-to-M: 34), and 4 gag/0 mt copies. The two PERV-positive salivary glands contained 14 gag/1 mt copies, and 28 gag/0 mt copies. The ovary and the kidney contained 46 gag/3 mt and 69 gag/0 mt copies, respectively. The PERV-positive human tumour contained 47 gag/3 mt copies. CONCLUSIONS/INTERPRETATION: Microchimerism and PERV transmission were frequently observed in both mouse and human tissues during grafting of pig PK15 cells into nude mice bearing human tumours, and sometimes during pig islet xenograft in this model. This strengthens the notion that there is a risk of transmitting PERV during pig islet xenograft.

[Medial approaches to the distal humerus for fracture fixation]. / Les voies médiales pour l'ostéosynthèse des fractures des deux tiers distaux de l'humérus.

PURPOSE OF THE STUDY: We report our experience with the medial and medioposterior approaches to the humeral diaphysis for plate fixation of the proximal humerus. MATERIAL AND METHODS: Fifteen patients were treated for shaft fracture (n=13) or nonunion (n=2) of the distal third of the humerus without radial nerve involvement. The medial approach was performed in the supine position and the medioposterior approach in the prone position. Bone healing was achieved in all cases. Three patients experienced sensorial irritation in the territory of the median nerve after the medial approach; one case did not regress. There were no complications with the medioposterior approach. DISCUSSION: Dissection of the radial nerve can be avoided with these two approaches which also have a cosmetic advantage. The medioposterior approach appears to be preferable because of the comfortable operative position and the absence of risk for the median nerve. Both approaches are however contraindicated if there is preoperative involvement of the radial nerve.

Long-term follow-up failed to detect in vitro transmission of full-length porcine endogenous retroviruses from specific pathogen-free pig islets to human cells.

AIMS/HYPOTHESIS: Islets from specific pathogen-free (SPF) pigs could prevent the transmission of conventional zoonosis, but not endogenous retroviruses (PERV), from pigs to diabetic patients. We previously reported that the pancreas showed the lowest expression of PERV mRNA among pig tissues intended for grafting. This study aimed to determine whether PERV from pig islets infect human cells during co-incubation. METHODS: Human cells (including highly PERV-sensitive 293 cells) were incubated with SPF pig islet cells under conditions designed to increase contact (a high islet to human cell ratio, extended period of co-culture, and repeated contacts). PK15 and G2 retrovirus-producing pig cells were used in place of islet cells as "positive infection controls". Infection of human cells was monitored on cellular extracts and supernatants by PCR or long PCR, and RT-PCR or long RT-PCR, to detect PERV DNA and mRNA, respectively. Reverse-transcriptase activity was monitored by PERT. RESULTS: Despite the presence of all PERV sequences in pig islet cells, including full-length inserts, no DNA or RNA for gag, pol, and the 3 env sub-types were detected in any human cell line or blood mononuclear cells incubated with pig islet cells, during an 18-week follow-up period. No PERV sequences or RT activity were detected in supernatants. PERV signals were negative even when the pig islet to human cell ratio was increased to 100:1, the time of co-culture was extended to 5 days and two sequential co-incubations were done. By contrast, all PERV DNA and mRNA were detected in all human cells co-incubated with PK15 or G2 cells. Depending on human cell types, productive or non-productive infections were obtained: full-length PERV RNA and RT activity in supernatants were detected or not; and PERV sequences to previously unexposed human cells by PERV-infected human cells were transmitted or not. Some human cells were not productively infected by PK15 cells but became productively infected after co-incubation with PERV-infected 293 cells. CONCLUSION/INTERPRETATION: SPF pig islet cells, even with PERV inserts and transcripts, have very little probability of transmitting PERV to human cells during co-incubation. The sensitivity of human cells to stable and productive infection by PERV depends on the cell type. Human adaptation of PERV was observed.

Human growth hormone locally released in bone sites by calcium-phosphate biomaterial stimulates ceramic bone substitution without systemic effects: a rabbit study.

Calcium-phosphate bone replacement biomaterial has been used as a drug carrier for therapeutic agents. This study investigated the efficacy of local administration of human growth hormone (hGH) by macroporous biphasic calcium phosphate (MBCP) implants in improving the bone substitution qualities of ceramics. hGH release from MBCP implants loaded with 1 microg of hGH was rapid during the first 48 h and then sustained for a total of 9 days. Immunolocalization of hGH in vitro and in vivo by transmission electron microscopy showed its presence inside the material, indicating that it was able to penetrate within the porosity of the ceramic during the adsorption process. MBCP cylinders (6 x 6 mm) were loaded with 0.1, 1, and 10 microg of hGH and implanted into rabbit femurs (n = 40). The effects of locally released hGH on bone ingrowth and ceramic resorption were evaluated by scanning electron microscopy and image analysis. The results indicated that hGH increased bone ingrowth (+65%) and ceramic resorption (+140%) significantly in comparison with control implants and that the increase was dose dependent. Biochemical parameters monitored in rabbit plasma and urine, as well as the absence of any significant difference between contralateral implants and the control, indicated that hGH did not produce detectable systemic effects. Thus, the use of MBCP appears to be effective for local delivery of hGH, resulting in improved bone substitution.

[Extemporaneous femoral lengthening by the Cauchoix technic in children and adolescents]. / L'allongement fémoral extemporané suivant la technique de Cauchoix chez l'enfant et l'adolescent.

One hundred and thirty-eight femoral lengthening operations have been performed in 133 children. The etiology of the shortening was poliomyelitis in 71, infection in 20 and congenital abnormalities in 28. The femur was lengthened in one operative stage by step-cut osteotomy, immediate traction and plate fixation. The mean gain was 35 mm with a maximum of 55 mm. The range of knee movement was unaffected except in 6 cases. Infection occurred in 2 patients without prejudicing the final result. Bony union was obtained in all cases, bone grafting being necessary only once. One permanent sciatic palsy was seen. Thirteen fractures occurred in 9 femurs. Two occurred during operation with loss of lengthening in one case. Eleven occurred post-operatively at the site of osteotomy. One case fractured on 3 occasions. Two cases fractured in another portion of the femur. The complications became fewer with experience and with more accurate technique and it is concluded that the method is safer than progressive lengthening at least in moderate limb length discrepancy.

Adult lumbar scoliosis.

This report details the expierience with adult lumbar scoliosis among patients at a scoliosis center. Some curves are shown to progress in the adult, while others appear de novo. Pain arising in adult scoliosis may reflect root compression or segmental degeneration. Once pain arises in an adult lumbar curve, it is likely to be progressive and often requires surgical treatment.

[Pyogenic spondylitis in adults]. / Spondylodiscites à pyogénes de l'adulte

The authors have treated 50 cases of non specific spondylitis in adults and reviewed the clinical signs and diagnostic problems in this condition. They advocate a systematic surgical approach to the focus. This allows identification of the organism unless the patient has previously received antibiotics. Even then, a direct approach allows histological examinations to be made and necrotic and infected tissues to be cleaned up. In 12 highly destructive lesions, a bone graft was added. The results were more satisfactory when fusion across the disc was achieved. There were only two deaths.