Preventable deaths in a French regional trauma system: A six-year analysis of severe trauma mortality.

BACKGROUND: Analyzing mortality in a mature trauma system is useful to improve quality of care of severe trauma patients. Standardization of error reporting can be done using the classification of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO). The aim of our study was to describe preventable deaths in our trauma system and to classify errors according to the JCAHO taxonomy. METHODS: We performed a six-year retrospective study using the registry of the Northern French Alps trauma network (TRENAU). Consecutive patients who died in the prehospital field or within their stay at hospital were included. An adjudication committee analyzed deaths to identify preventable or potentially preventable deaths from 2009 to 2014. All errors were classified using the JCAHO taxonomy. RESULTS: Within the study period, 503 deaths were reported among 7484 consecutive severe trauma patients (overall mortality equal to 6.7%). Seventy-two (14%) deaths were judged as potentially preventable and 36 (7%) deaths as preventable. Using the JACHO taxonomy, 170 errors were reported. These errors were detected both in the prehospital setting and in the hospital phase. Most were related to clinical performance of physicians and consisted of rule-based or knowledge based failures. Prevention or mitigation of errors required an improvement of communication among caregivers. CONCLUSIONS: Standardization of error reporting is the first step to improve the efficiency of trauma systems. Preventable deaths are frequently related to clinical performance in the early phase of trauma management. Universal strategies are necessary to prevent or mitigate these errors.

Long-term outcomes of patients with 10 or more colorectal liver metastases.

BACKGROUND: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. METHODS: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. RESULTS: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. CONCLUSIONS: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.

Abbreviated laparotomy or damage control laparotomy: Why, when and how to do it?

The goal of abbreviated laparotomy is to treat severely injured patients whose condition requires an immediate surgical operation but for whom a prolonged procedure would worsen physiological impairment and metabolic failure. Indeed, in severely injured patients, blood loss and tissue injuries enhance the onset of the "bloody vicious circle", triggered by the triad of acidosis-hypothermia-coagulopathy. Abbreviated laparotomy is a surgical strategy that forgoes the completeness of operation in favor of a physiological approach, the overriding preference going to rapidity and limiting the procedure to control the injuries. Management is based on sequential association of the shortest possible preoperative resuscitation with surgery limited to essential steps to control injury (stop the bleeding and contamination), without definitive repair. The latter will be ensured during a scheduled re-operation after a period of resuscitation aiming to correct physiological abnormalities induced by the trauma and its treatment. This strategy necessitates a pre-defined plan and involvement of the entire medical and nursing staff to reduce time loss to a strict minimum.

Management of blunt hepatic trauma.

For the last 20 years, nonoperative management (NOM) of blunt hepatic trauma (BHT) has been the initial policy whenever this is possible (80% of cases), i.e., in all cases where the hemodynamic status does not demand emergency laparotomy. NOM relies upon the coexistence of three highly effective treatment modalities: radiology with contrast-enhanced computerized tomography (CT) and hepatic arterial embolization, intensive care surveillance, and finally delayed surgery (DS). DS is not a failure of NOM management but rather an integral part of the surgical strategy. When imposed by hemodynamic instability, the immediate surgical option has seen its effectiveness transformed by development of the concept of abbreviated (damage control) laparotomy and wide application of the method of perihepatic packing (PHP). The effectiveness of these two conservative and cautious strategies for initial management is evidenced by current experience, but the management of secondary events that may arise with the most severe grades of injury must be both rapid and effective.

Management of splenic and pancreatic trauma.

The spleen and pancreas are at risk for injury during abdominal trauma. The spleen is more commonly injured because of its fragile structure and its position immediately beneath the ribs. Injury to the more deeply placed pancreas is classically characterized by discordance between the severity of pancreatic injury and its initial clinical expression. For the patient who presents with hemorrhagic shock and ultrasound evidence of major hemoperitoneum, urgent "damage control" laparotomy is essential; if splenic injury is the cause, prompt "hemostatic" splenectomy should be performed. Direct pancreatic injury is rarely the cause of major hemorrhage unless a major neighboring vessel is injured, but if there is destruction of the pancreatic head, a two-stage pancreatoduodenectomy (PD) may be indicated. At open laparotomy when the patient's hemodynamic status can be stabilized, it may be possible to control splenic bleeding without splenectomy; it is always essential to search for injury to the pancreatic duct and/or the adjacent duodenum. Pancreatic contusion without ductal rupture is usually treated by drain placement adjacent to the injury; ductal injuries of the pancreatic body or tail are treated by resection (distal pancreatectomy with or without splenectomy), with generally benign consequences. For injuries of the pancreatic head with pancreatic duct disruption, wide drainage is usually performed because emergency PD is a complex gesture prone to poor results. Postoperatively, the placement of a ductal stent by endoscopic retrograde catheterization may be decided, while management of an isolated pancreatic fistula is often straightforward. Non-operative management is the rule for the trauma victim who is hemodynamically stable. In addition to the clinical examination and conventional laboratory tests, investigations should include an abdominothoracic CT scan with contrast injection, allowing identification of all traumatized organs and assessment of the severity of injury. In this context, non-operative management (NOM) has gradually become the standard as long as the patient remains hemodynamically stable and there is no suspicion of injury to hollow viscera, with the patient being carefully monitored on a surgical service. The development of arteriography with splenic artery embolization has increased the rate of splenic salvage; this can be performed electively based on specific indications (blush on CT, pseudoaneurysm, arteriovenous fistula), and may also be considered for severe splenic injury, abundant hemoperitoneum, or severe polytrauma. For pancreatic injury, in addition to CT scan, magnetic resonance pancreatography (MRCP) or even endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to identify a ductal rupture. If the pancreatic duct is intact, laboratory and CT imaging surveillance is performed just as for splenic injury. In case of pancreatic ductal injury, ERCP stenting can be considered. However, if this is unsuccessful, the therapeutic decision can be difficult: while NOM can still be successful, complications may arise that are difficult to treat while distal pancreatectomy, although initially more agressive may avoid these complications if performed early.

Management of pancreatic trauma.

INTRODUCTION: Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. MATERIAL AND METHODS: Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. RESULTS: Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. CONCLUSION: In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

Frequent intragenic rearrangements of DPYD in colorectal tumours.

Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.

Is port-site resection necessary in the surgical management of gallbladder cancer?

INTRODUCTION: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed "benign" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry. METHODS: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. RESULTS: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. CONCLUSION: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment.

Hepatic artery ligation for arterial rupture following liver transplantation: a reasonable option.

Hepatic artery (HA) rupture after liver transplantation is a rare complication with high mortality. This study aimed to review the different managements of HA rupture and their results. From 1997 to 2007, data from six transplant centers were reviewed. Of 2649 recipients, 17 (0.64%) presented with HA rupture 29 days (2-92) after transplantation. Initial management was HA ligation in 10 patients, reanastomosis in three, aorto-hepatic grafting in two and percutaneous arterial embolization in one. One patient died before any treatment could be initiated. Concomitant biliary leak was present in seven patients and could be subsequently treated by percutaneous and/or endoscopic approaches in four patients. Early mortality was not observed in patients with HA ligation and occurred in 83% of patients receiving any other treatment. After a median follow-up of 70 months, 10 patients died (4 after retransplantation), and 7 patients were alive without retransplantation (including 6 with HA ligation). HA ligation was associated with better 3-year survival (80% vs. 14%; p=0.002). Despite its potential consequences on the biliary tract, HA ligation should be considered as a reasonable option in the initial management for HA rupture after liver transplantation. Unexpectedly, retransplantation was not always necessary after HA ligation in this series.

[Early embolization in the non-operative management of blunt splenic injuries: a retrospective multicenter study]. / L'embolisation précoce dans le traitement non opératoire des traumatismes fermés de la rate. Etude rétrospective multicentrique.

AIM OF THE STUDY: Splenic artery embolization has been used as an adjunct to the non-surgical management of blunt splenic injury. No consensus on its indications has emerged from the literature. This multicentric study aimed to evaluate the results of this technique in France. PATIENTS AND METHODS: Between March 2000 and April 2006, 22 patients older than 15 years of age (mean age 29, range: 15-59) with splenicv rupture due to blunt trauma underwent splenic artery embolization in six Level I Trauma Centers in France. Splenic rupture was classified Moore II in 3 cases, Moore III in 12 cases, and Moore IV in 7 cases. Angiography was performed within 4 hours of admission in half of the cases. The main indications for splenic artery embolization were: extravasation of contrast medium on CT scan (10 cases, 45%); early pseudo-aneurysm (6 cases, 23%); hypotension despite fluid resuscitation and/or progressive need for transfusion (5 cases, 22%). RESULTS: There was no mortality. Nine patients experienced complications (41%) including 6 (27%) who developed left pleural effusion. Two patients eventually underwent splenectomy (one for persistent hemorrhage, one for splenic necrosis). The overall splenic salvage rate was 91%. CONCLUSION: Splenic artery embolization is a valuable techniche that hels to lower the rate of splenectomy for traumatic splenic rupture with relatively low morbidity.

Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer.

BACKGROUND: In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression. METHODS: Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR-restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay. RESULTS: The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16. CONCLUSIONS: Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.

[Abbreviated laparotomy in severe abdominal trauma]. / La laparotomie écourtée pour le traitement des traumatismes abdominaux sévères.

On critically injured patient the decision to perform a damage control laparotomy is based on the volume of transfusion and shock. The aim of the surgery which is to obtain as fast as possible the best hemostasis to limit the peritoneal thermal loss and to perform as soon as possible physiologic restoration in the Intensive Care Unit.

EGFR in colorectal cancer: more than a simple receptor.

BACKGROUND: Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). METHOD: The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). FINDINGS: A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. INTERPRETATION: These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.

[Laparostomy with vacuum pack technique]. / La laparostomie par pansement pariétal aspiratif ou "Vacuum Pack".

The technique of abdominal wall closure by vacuum pack is described. Indications are essentially the abbreviated laparotomy or damage control (especially with abdominal packing), and the post traumatic abdominal compartment syndrome (in the treatment and prevention).

[Traumatic pancreatic injuries]. / Traumatismes du pancréas.

If an emergency laparotomy is necessary, a damage control laparotomy may be useful. If during the laparotomy the hemodynamic is stabilised, the severity is depending on the existence of a ductal injury and an associated duodenal lesion. Surgical indications and techniques are described in these different cases. If no laparotomy, the location and type of injury is assessed by CT scan, magnetic resonance cholangiopancreatography or ERCP. Injury of the pancreatic duct is the main part of prognosis and indications. The non operative treatment in case of ductal injury remains controversial.