Is targeting autophagy a promising lead to unveil the cloak of invisibility in pancreatic cancer?

Pancreatic ductal adenocarcinoma PDAC is considered as one of the less immunogenic solid tumor types. Pancreatic tumors are also known to present a high autophagy flux which supports tumor progression. Autophagy was recently described as a tumor-intrinsic immune escape process during tumor development by sequestration of Major Histocompatibility Complex class I (MHC-I) inside the PDAC cells. We comment this discovery and discuss the implications on how to limit immune escape in patients and how to improve immunotherapy efficiency. Currently, pancreatic adenocarcinoma is the most frequent pancreatic cancer with a poor prognosis, an important lethality, and a 5-year overall survival less than 5%. The development of some therapeutic solutions like targeted therapies are promising [1]. However, it is still important to understand this morbid pathology to improve the treatment, because PDAC is predicted to be the second leading cause of death in Western countries [2].

Evaluation of a fellowship abroad as part of the initial training of the French military surgeon.

INTRODUCTION: Military surgery requires skills that in general cannot be easily learnt in civilian training. Participation in a fellowship abroad adapted to the particular operating conditions of the foreign deployment is one route that might secure the necessary supplementary training. We therefore assessed the relevance of such a fellowship in the preparedness of young military surgeons in their first deployment. METHODS: This study included all active military surgeons who had completed a fellowship abroad during their initial training from 2004 to 2017 in Tchad or Senegal or Djibouti. The collection of data was performed using a questionnaire. The main judgement criterion was the rate of positive answers awarded to the relevance of this fellowship in the preparedness of respondents' first foreign deployment. RESULTS: Sixty-nine of 73 surgeons answered. Sixty-one estimated the fellowship had allowed them to feel more operational during their first mission, with 83.61% rating this feeling as important. Also, 61 recommended the use of a fellowship for war surgery training. The grade assigned to the surgical benefit was 8.48/10. CONCLUSION: A fellowship abroad permits one to become familiar with surgical practice under austere circumstances and the particularities of the surgical structures at the front. Current trainees' feedback confirms its relevance.

Type III open tibia fractures in low-resources setting. Part 3: achievement of bone union and treatment of segmental bone defects.

After presentations of the principles of limb salvage and soft-tissue coverage for Gustilo III open tibia fractures, this third part is dedicated to management of tibial non-unions in low-resource settings. Inter-tibiofibular grafting and the induced membrane technique are preferred because they make it possible to deal with almost all situations. Key technical points of these methods are presented, followed by treatment guidelines based on Catagni's classification and bone defect size.

Metacarpal bone reconstruction by a cementless induced membrane technique.

Gunshot wounds to the hand often produce complex injuries and large segmental bone defects. Bone reconstruction remains a challenge in this context. The induced membrane technique is a simple and effective procedure for reconstruction of segmental bone defects. The technique is straightforward but must be performed rigorously. Usually polymethylmethacrylate (PMMA) cement is required for the first stage of the surgery. We describe four cases of metacarpal bone reconstruction after gunshot wounds in a limited-resource setting. Two patients were treated using the induced membrane technique with a polypropylene syringe body instead of PMMA cement, which was unavailable in this situation. A thick membrane was observed 6 weeks after spacer implantation. Bone union was achieved in all cases.

Application of damage control orthopedics to combat-related hand injuries.

The purpose of this report was to analyze sequential management of patients with combat-related hand injuries in the Kabul International Airport Combat Support Hospital and to identify principles of hand damage control orthopedics (DCO). A retrospective study was conducted using the French Opex data system that included all the patients who received sequential treatment for combat-related hand injuries from 2009 to 2013. Demographics, mechanism, injury pattern, reasons for DCO application and surgical procedures performed during initial and definitive treatment were described. Forty-one patients were included: 14 French soldiers and 27 Afghan patients. Explosive devices were the most common injury mechanism. There were multiple reasons for DCO application in 20 cases. Debridement, skeletal fixation by pinning or splinting, and delayed primary closure were the main emergent procedures. Primary and secondary treatment data did not differ between French and Afghan patients. Although Afghan patients were fully treated on site, the time to secondary procedures was three time higher in this group because of intense operational activity during the period study. The functional outcome was only evaluated in French soldiers who were treated definitely in France. Hand DCO may be required in various situations encountered in both military and civilian settings: polytrauma; delayed transfer to hand specialist; complex high-energy injuries due to firearms or explosive devices. The basic elements of this specific surgical tactic are meticulous debridement, detailed wound assessment and temporary skin coverage.

Type III open tibia fractures in low-resources setting. Part 1: strategy and principles of limb salvage.

In developing countries, road traffic accidents result in many cases of open trauma, especially fractures, with the tibia area at particular risk in motorcycle crashes. Despite a high prevalence of severe leg trauma with multi-tissue injuries, few studies have focused on the challenge of their reconstruction in these limited-resource settings. The first part of this review presents the surgical strategy. Limitations and principles of initial limb salvage are detailed. Orthopedic procedures for early damage control, based on debridement and temporary bone stabilization, are often required. The priority is to shorten the time to initial surgical management to avoid infection, which jeopardizes reconstruction.

Extensive septic myonecrosis related to compartment syndrome: is the upper extremity salvage achievable in precarious setting?

Management of acute compartment syndrome is well known and based on emergent and generous fasciotomies. In absence of such fasciotomies, or if they are performed too late, the compartment syndrome leads to a Volkmann's syndrome or to a dramatic septic myonecrosis raising the question of an amputation. However, salvage treatment of these extreme clinical presentations may be preferable at the upper extremity, particularly in developing countries where access to sophisticated prosthetic devices is limited. The authors report four typical observations about management of upper extremity delayed compartment syndromes with severe infectious complications. To clarify treatment principles and pitfalls, two situations are distinguished: subacute septic myonecrosis and chronic osteomyelitis. Management specificities of both situations are discussed according to literature data and available resources in austere environments. Despite challenging in low-resources setting, upper extremity salvage is possible at the cost of simple but iterative surgical procedures. Limitations are represented by the need of repeated blood transfusions in the subacute phase, and difficulties in providing medical treatment of bone infection in the chronic phase.

Microbiology of French military casualties repatriated from overseas for an open traumatic injury.

BACKGROUND: This study aimed to describe the microbiological epidemiology of repatriated French soldiers with an open traumatic injury, and to measure the proportion of multidrug-resistant bacteria (MDRB). METHODS: Retrospective study including all French soldiers repatriated in 2011 and 2012 in Parisian military hospitals for open traumatic injury. Results of clinical samples and MDRB screening were collected. The antibiotic susceptibility was assessed using the agar disk diffusion method. Characterization of resistance mechanisms was performed using PCR. Genotyping of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) isolates was performed using rep-PCR. RESULTS: A total of 139 patients were included; 70% of them were repatriated from Afghanistan. At admission, 24/88 were positive for MDRB (28%), mainly ESBL-E but no carbapenemase-producing Enterobacteriaceae and vancomycin-resistant Enterococcus faecium were identified. Forty-five patients had lesion sample collection, and 28/45 had a positive culture. The most frequently isolated pathogens were Enterobacter cloacae, Pseudomonas aeruginosa, and Escherichia coli. For eight patients, a MDRB was isolated from the wound, mainly ESBL-E (7/8) but also one methicillin-resistant Staphylococcus aureus and one imipenem-resistant Acinetobacter baumannii. Among ESBL-E, the PCR evidenced the high prevalence of CTX-M15 enzymes. Rep-PCR performed on the 23 ESBL-producing E. coli isolates highlighted numerous profiles. CONCLUSIONS: Controlling the spread of ESBL-E is currently challenging for French Armed Forces. Despite any evidence of an epidemic clone, a high-level compliance with hygiene precautions is required throughout the chain of care to avoid cross contamination.

Temporary fixation of limbs and pelvis.

"Urgent, complete, definitive" treatment still today seems to be an appropriate attitude in many trauma cases. There are, however, several situations in which emergency definitive fixation is not the optimal strategy for all cases of fracture. Temporary fixation has a role to play in the orthopedic "trauma damage control" design comprising successive steps, as applied in multiple trauma, multiple fracture, severe multi-tissue limb lesions and soft-tissue lesions of unpredictable progression. The aim of this study is to define the strategies, indications, principles and limitations of temporary fixation in limb and pelvis fracture.

Could the orthopaedic surgeon deployed in austere setting perform flaps on the leg?

The orthopaedic military surgeons deployed in operations are led to perform soft tissue coverage on the lower limb. The purpose of this study was to evaluate if flaps performed by surgeons' non-specialist in reconstructive surgery are associated with good outcome. All patients operated for a flap on the leg in French Forward Surgical Team deployed in theatre of operations between 2003 and 2013 were retrospectively reviewed. Forty-nine patients were included, for a total of 54 flaps' procedures. Indications were open fractures in 25 cases and osseous infections in 29 cases. No flap was performed on French soldiers. All the flaps were pedicle. Outcome was favourable for more than 90% of flaps with no statistical difference between muscular and fasciocutaneous flap and with regard to the indication. In conclusion, an orthopaedic surgeon deployed in austere setting with significant good outcome can perform reconstructive surgery with legs' flaps.

Limb reconstructive surgery in austere settings: use of flaps in French forward surgical facilities.

INTRODUCTION: Military surgeons deployed abroad must achieve soft tissue coverage under austere conditions. HYPOTHESIS: A non-specialized surgeon can achieve soft tissue coverage with good results. MATERIAL AND METHOD: This is a retrospective study of all patients who underwent soft tissue coverage in French forward surgical units between 2003 and 2013. RESULTS: In all, 81 flaps were constructed. Open fractures (39%) were the leading indication, followed by osseous infections (35%). Most flaps were for legs (70%) and hands (25%). Only pedicle flaps were used. The success rate was 91%. DISCUSSION: Flaps can be constructed by orthopedic surgeons who are not specialized in reconstructive surgery, in austere settings and with good results. This procedure must be part of a global strategy of limb reconstruction, especially in cases of bone and joint infection. Pedicle flaps, especially muscular, appear more reliable and are to be preferred. The training of the surgeons deployed abroad must include flap surgery.

The French Advanced Course for Deployment Surgery (ACDS) called Cours Avancé de Chirurgie en Mission Extérieure (CACHIRMEX): history of its development and future prospects.

INTRODUCTION: The composition of a French Forward Surgical Team (FST) has remained constant since its creation in the early 1950s: 12 personnel, including a general and an orthopaedic surgeon. The training of military surgeons, however, has had to evolve to adapt to the growing complexities of modern warfare injuries in the context of increasing subspecialisation within surgery. The Advanced Course for Deployment Surgery (ACDS)-called Cours Avancé de Chirurgie en Mission Extérieure (CACHIRMEX)-has been designed to extend, reinforce and adapt the surgical skill set of the FST that will be deployed. METHODS: Created in 2007 by the French Military Health Service Academy (Ecole du Val-de-Grâce), this annual course is composed of five modules. The surgical knowledge and skills necessary to manage complex military trauma and give medical support to populations during deployment are provided through a combination of didactic lectures, deployment experience reports and hands-on workshops. RESULTS: The course is now a compulsory component of initial surgical training for junior military surgeons and part of the Continuous Medical Education programme for senior military surgeons. From 2012, the standardised content of the ACDS paved the way for the development of two more team-training courses: the FST and the Special Operation Surgical Team training. The content of this French military original war surgery course is described, emphasising its practical implications and future prospects. CONCLUSION: The military surgical training needs to be regularly assessed to deliver the best quality of care in an context of evolving modern warfare casualties.

[Severe leg trauma in a resource-poor environment: indications for amputation in emergencies]. / Traumatismes graves du segment jambier en milieu précaire: place de l'amputation en urgence.

Although the development of multitissue limb reconstruction has reduced the role of post-traumatic primary amputation of the leg, some patients should nonetheless undergo emergency amputations. In developing countries, the socioeconomic context associated with the limited health care supply compromises still further the prognosis of preservation efforts. The decision criteria for surgery are thus different in these settings. The choice of emergency leg amputation or attempted preservation in developing countries depends on the epidemiology of severe leg trauma, the local and general prognosis, and the practice conditions. Three factors must be combined before limb preservation can be attempted: adequate local and general adequate wound elements, an available, experienced surgeon with a competent care structure, and a favorable social context.

[Idiopathic bilateral patellar tendon rupture]. / Rupture bilatérale idiopathique du tendon rotulien.

In the absence of systemic disease, specific treatment or sport tendonitis, simultaneous bilateral patellar tendon rupture is rare. Often missed on the first glance, it represents a diagnostic difficulty that should not be overlooked at the initial medical visit. The loss of active extension of the lower limb and a radiographic patella alta, even in a bilateral context, should raise suspicion of this diagnosis. It is then necessary to search for predisposing causes and to evoke the differential, or frequently associated, diagnoses. The present report illustrates these diagnostic difficulties and summarizes some clinical considerations that might help to avoid neglecting these different elements at the first medical visit (positive diagnosis, associated lesions, favouring factors).

War-related extremity injuries in children: 89 cases managed in a combat support hospital in Afghanistan.

BACKGROUND: Meeting paediatric needs is among the priorities of western healthcare providers working in Afghanistan. HYPOTHESIS: Insufficient information is available on paediatric wartime injuries to the extremities. Our objective here was to describe these injuries and their management on the field. MATERIALS AND METHODS: We retrospectively reviewed consecutive cases of injuries to the extremities in children (< 16 years of age) due to weapons and managed at the Kabul International Airport (KaIA) Combat Support Hospital between June 2009 and April 2013. We identified 89 patients with a mean age of 10.2 ± 3.5 years and a total of 137 elemental lesions. RESULTS: Explosive devices accounted for most injuries (78.6%) and carried a significantly higher risk of multiple lesions. There were 54 bone lesions (traumatic amputations and fractures) and 83 soft-tissue lesions. The amputation rate was 18%. Presence of bone lesions was associated with a higher risk of injury to blood vessels and nerves. Of the 89 patients, four (4.5%) died and eight (9%) were transferred elsewhere. Of the 77 remaining patients, at last follow-up (median, one month; range, 0.1-16 months), 73 (95%) had achieved a full recovery (healed wound and/or fracture) or were recovering with no expectation that further surgery would be needed. DISCUSSION: Despite the absence of paediatric surgeons, the combat support hospital provided appropriate care at the limb salvage and reconstruction phases. The highly specialised treatments needed to manage sequelae were very rarely provided. These treatments probably deserve to be developed in combat support hospitals.

French surgical experience in the role 3 medical treatment facility of KaIA (Kabul International Airport, Afghanistan): the place of the orthopedic surgery.

INTRODUCTION: In 2009, the French took command of the Medical Hospital (MH) or Role 3 Hospital at KaIA (Kabul International Airport) within the framework of its role in the military mission Operation Pamir in Afghanistan. The goal of this study was to analyze the volume of orthopedic surgical activity for the last four years, to identify its specificities and to improve training of military orthopedic surgeons. HYPOTHESIS: Orthopedic surgery is the most important activity in the field and surgeons must adapt to situations and injuries that are different from those encountered in France. PATIENTS AND METHODS: All patients operated on between July 2009 and June 2013 were prospectively included in an electronic database. The analysis included the number of surgical acts and patients, the types of injuries and the surgical procedures. RESULTS: Forty-three percent (n=1875) of 4318 procedures involved orthopedic surgery. Half of these were emergencies. French military personnel represented 17% of the patients, local civilians 47% and children 17%. Half of the procedures involved the soft tissues, 20% were for bone fixation and 10% for surgery of the hand. The rate of amputation was 6%. The diversity of the surgical acts was high ranging from emergency surgery to surgical reconstruction. DISCUSSION: The activity of this Role 3 facility is comparable to that of other Role 3 facilities in Afghanistan, with an important percentage of acts involving medical assistance to the local population and scheduled surgeries as well as primary and/or secondary management of the wounded. The diversity of surgical acts confirms the challenge of training military orthopedic surgeons within the context of the hyperspecialization of the civilian sector. Specific training has been organized in France by the École du Val de Grâce. Specific continuing education is also necessary. LEVEL OF EVIDENCE: IV (retrospective review).

Wartime upper extremity injuries: experience from the Kabul International Airport combat support hospital.

Few epidemiologic studies have been published about the surgical management of wartime upper extremity injuries (UEIs). The purpose of the present report was to analyze upper extremity combat-related injuries (CRIs) and non-combat related injuries (NCRIs) treated in the Kabul International Airport Combat Support Hospital. A retrospective study was conducted using the French surgical database OpEX (French military health service) from June 2009 to January 2013. During this period, 491 patients with a mean age of 28.7 ± 13 years were operated on because of an UEI. Among them, 244 (49.7%) sustained CRIs and 247 (50.3%) sustained NCRIs. A total number of 558 UEIs were analyzed. Multiple UEIs and associated injuries were significantly more common in the CRIs group. Debridement was the most common procedure in both groups. External fixator application, delayed primary closure and flap coverage were predominant in the CRIs group, as well as internal fracture fixation and tendon repair in the NCRIs group. The overall number of surgical episodes was significantly higher in the CRIs group. Due to the high frequency of UEIs in the theatres of operations, deployed orthopedic surgeons should be trained in basic hand surgery. Although the principles of CRIs treatment are well established, management of hand NCRIs remains controversial in this setting.

Surgical management of combat-related upper extremity injuries.

This review presents the current surgical management of combat-related upper extremity injuries during the acute phase. The strategy consists of saving the life, saving the limb and retaining function. Surgical tactics are based on damage control orthopaedics techniques of haemorrhage control, wound debridement, and temporary bone stabilization prior to evacuation out of the combat zone. Features of the definitive management of local casualties in battlefield medical facilities are also discussed. In this situation, reconstructive procedures have to take into account the limited resources and operational constraints.

[Adolescents consulting at the pediatric emergency room for psychological or psychiatric reasons]. / Accueil en urgence des adolescents pour motif pédopsychiatrique.

INTRODUCTION: The number of pediatric emergency consultations for psychological or psychiatric reasons continues to rise, raising the question of the adequacy of existing facilities. Our aim was therefore to identify and characterize a population of adolescents consulting at the pediatric emergency unit at Rouen university hospital. METHODS: This study was conducted from 1 January to 31 December 2006. We distinguished three types of variables in adolescents consulting at the pediatric emergency unit. The main objective was to describe the profile and requirements of these young patients and their subsequent care management as compared to that of other studies. RESULTS: Of the 400 patients consulting over 12years of age, 69% were female and the average age was 13.8years. These cases were mainly attempted suicide in girls and conduct disorder in boys; hospitalization was at the request of the family. These consultations were directly linked to the school calendar and 70% required hospitalization. DISCUSSION: We both analyzed and compared the results of this study to those of other studies to propose solutions to improve the care of these young patients.

Current issues with lower extremity amputations in a country at war: experience from the National Military Hospital of Kabul.

PURPOSE: Management practices associated with war-related amputations in countries at war may be different from the recommendations of occidental Health Force Services due to the high numbers of wounded persons to treat in precarious conditions. This observational retrospective study documents the current management of local lower extremity amputees in Afghanistan. Surgical practices, with or without delayed primary closure (DPC), and prosthetic rehabilitation issues are analyzed. METHODS: This retrospective study was conducted in the National Military Hospital (NMH) of Kabul from May 2011 to November 2011. Fifty-four Afghan patients who underwent a lower extremity combat-related amputation were included. Ten of them sustained a bilateral amputation. RESULTS: Injuries were caused by improvised explosive devices (IEDs) or mines in 48 cases, bullets in three cases, and exploding shell fragments in three cases. Of the 64 amputations studied, 46 were open length preserving amputations and primary closure (PC) was applied in 18 cases. Patients were reviewed with a mean follow-up of 5.4 months (range 1-28 months). In the DPC group, secondary closure was performed with a mean time of 18.7 days (range 4-45 days) from injury. The proportion of infectious complications seemed to be higher in the PC group (5/18) than in the DPC group (3/46), but it was only a statistical trend (p = 0.1). Forty-three patients were not prosthetic fitted at the last follow-up. CONCLUSION: This study supports the surgical strategy of a two-stage procedure for lower limb amputations in countries at war, but underlines the problems of late secondary closure and prosthetic fitting related to decreased sanitary conditions.