Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection.

BACKGROUND: The prognosis of patients with pancreatic cancer remains poor and novel therapeutic targets are required urgently. Treatment resistance could be due to the tumour microenvironment, a desmoplastic stroma consisting of cancer-associated fibroblasts and tumour-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and cancer-associated fibroblasts (CAFs) in pancreatic cancer of the body and tail. METHODS: Using tissue microarray from resected left-sided pancreatic cancer specimens, the immunohistochemistry of TILs (cluster of differentiation (CD) 45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and α-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki-67) was examined, and the association with disease-free (DFS) and overall (OS) survival investigated using a computer-assisted quantitative analysis. Patients were classified into two groups, with low or high levels or ratios, using the 75th percentile value as the cut-off. RESULTS: Forty-three patients were included in the study. Their median DFS and OS were 9 and 27 months respectively. A high CD4/CD3 lymphocyte ratio was associated with poorer DFS (8 months versus 11 months for a low ratio) (hazard ratio (HR) 2·23, 95 per cent c.i. 1·04 to 4·61; P = 0·041) and OS (13 versus 27 months respectively) (HR 2·62, 1·11 to 5·88; P = 0·028). A low αSMA/vimentin ratio together with a high CD4/CD3 ratio was correlated with poorer outcomes. No significant association was found between Ki-67, PD-L1 and survival. CONCLUSION: In patients with resected left-sided pancreatic cancer, a tumour microenvironment characterized by a high CD4/CD3 lymphocyte ratio along with a low αSMA/vimentin ratio is correlated with poorer survival.

ANTECEDENTES: El pronóstico del cáncer de páncreas sigue siendo malo y se requieren nuevas dianas terapéuticas de forma urgente. La resistencia al tratamiento podría ser atribuida al microambiente tumoral, un estroma desmoplásico compuesto por fibroblastos asociados al cáncer y linfocitos infiltrantes de tumor. El objetivo del estudio fue evaluar el valor pronóstico de los linfocitos infiltrantes de tumor y de los fibroblastos asociados al cáncer en el cáncer de cuerpo y cola de páncreas. MÉTODOS: Utilizando microarray para el análisis de muestras de tejido obtenidas tras la resección de cáncer de páncreas del lado izquierdo, se realizó inmunohistoquímica de linfocitos infiltrantes de tumor (CD45, CD3, CD4, FoxP3 y CD8), fibroblastos asociados al cáncer (vimentina y actina del músculo liso alfa (αSMA)) y marcadores funcionales (PD-L1 y Ki67), y se investigó la asociación con la supervivencia libre de enfermedad y la supervivencia global. Los resultados se obtuvieron tras un análisis cuantitativo asistido por ordenador. Los pacientes se clasificaron en dos grupos, de bajo y alto riesgo, utilizando el valor del percentil 75 como punto de corte. RESULTADOS: Se incluyeron 43 pacientes en el estudio. En esta población, la mediana de supervivencia libre de enfermedad y de supervivencia global fueron 9 meses y 27 meses, respectivamente. Una alta proporción de linfocitos CD4/CD3 se asoció a peor supervivencia libre de enfermedad (8 meses versus 11 meses; cociente de riesgos instantáneos, hazard ratio, HR 2,2; i.c. del 95% 1,0-4,6; P = 0,041) y supervivencia global (13 meses versus 27 meses; HR 2,6; i.c. del 95% 1,1-5,9; P = 0.028). Una baja proporción αSMA/vimentina junto con una alta proporción CD4/CD3 se correlacionó con peores resultados. No se encontró asociación significativa entre Ki67, PD-L1 y la supervivencia. CONCLUSIÓN: En pacientes con cáncer de páncreas izquierdo resecado, un microambiente tumoral caracterizado por una alta proporción de linfocitos CD4/CD3 junto con una baja proporción de αSMA/vimentina se correlaciona con una peor supervivencia.

Value of early repeated abdominal CT in selective non-operative management for blunt bowel and mesenteric injury.

OBJECTIVES: To evaluate the performance of an early repeated computed tomography (rCT) in initially non-operated patients with blunt bowel and mesenteric injuries (BBMI). METHODS: This was a monocentric retrospective observational study from 2009 to 2017 of patients with a BBMI on initial CT (iCT). Patients initially non-operated on were scheduled for a rCT within 48 h. Initial CT and rCT diagnostic performance were compared based on a surgical injury prediction score previously described. For statistical analysis, we used the chi-square analyses for paired data (McNemar test). RESULTS: Eighty-four patients (1.9% of trauma) had suspected BBMI on iCT. Among these patients, 22 (26.2%) were initially operated on, 18 (21.4%) were later operated on, and 44 (52.4%) were not operated on. The therapeutic laparotomy rate was 85%. Thirty-four patients initially non-operated on had a rCT. The absolute value of the CT scan score increased for 15 patients (44.1%). The early rCT diagnostic performance, compared with iCT, showed an increase in sensitivity (from 63.6 to 91.7%), in negative predictive value (from 77.4 to 94.7%), and in AUC (from 0.77 to 0.94). CONCLUSION: In initially non-operated patients with BBMI lesions, the performance of an early rCT improved the sensitivity of lesion detection requiring surgical repair and the security of patient selection for non-operative treatment. KEY POINTS: • Selective non-operative treatment for hemodynamically stable patients with blunt bowel and/or mesenteric injuries on CT is developing but remains controversial. • An early repeated CT improved the sensitivity of lesion detection requiring surgical repair and the security of patient selection for conservative treatment.

Bioabsorbable staple-line reinforcement for pancreatectomy in a porcine model: a preliminary study.

BACKGROUND: We conducted an exploratory study to assess the use of FOREseal® bioabsorbable reinforcement sleeves in stapling of the pancreatic parenchyma. METHODS: A left pancreatectomy was carried out with linear stapler on 12 pigs: in the FOREseal group (n = 6), the stapling was reinforced with FOREseal, while in the control group (n = 6), simple stapling was applied. RESULTS: The mean operating time was not different between the two groups. No additional haemostasis of the stapling transection was necessary with FOREseal, while in the control group, four pigs required additional haemostasis (p = 0.03). The mean postoperative drainage volume and the mean duration of drainage were, respectively, in the FOREseal group versus the control group: 82 versus 204 ml (p = 0.2) and 3.2 versus 4.7 days (p = 0.3). No adverse event occurred in the FOREseal group. There was no anatomopathological difference between the two groups. CONCLUSION: A good tolerance of FOREseal was observed when used on the pancreatic stump. In this study, it was demonstrated a better haemostatic control of the pancreatic stump with FOREseal which also tends to reduce the volume of postoperative drainage liquid.

[Appendicitis: yes or no to laparoscopic approach?]. / Appendicites: coelioscopie ou non?

Whether or not there is a benefit to laparoscopy versus open surgery in the management of acute appendicitis remains a subject of controversy despite the publication of numerous randomized studies. Operative time is longer for the laparoscopic approach. The incidence of abdominal wall abscess is decreased for laparoscopy but the incidence of deep intra-abdominal abscess may be increased, especially in the case of complicated appendicitis. Post-operative pain is diminished and resumption of normal activity is quicker with the laparoscopic approach. Hospitalization is shorter but the cost of hospital care is higher; nevertheless, the global cost may be less - particularly for patients whose return to work is hastened by a laparoscopic approach. Laparoscopy diminishes the number of normal appendectomies, particularly in women of reproductive age where the diagnosis may be unclear. Laparoscopic appendectomy is practicable and has advantages over open appendectomy under certain circumstances. These advantages are most evident in the young female, the working patient, and the obese patient. Overall, the advantages of laparoscopy are, at best, modest and clinical benefit is not always demonstrable. The risk of deep abscess, particularly in patients with perforated or gangrenous appendicitis, remains an unknown and should be evaluated by further studies.

Hollow viscus injury due to blunt trauma: A review.

Blunt abdominal trauma results in injury to the bowel and mesenteries in 3-5% of cases. The injuries are polymorphic including hematoma, seromuscular tear, perforation, and ischemia. They preferentially involve the small bowel and may result in bleeding and/or peritonitis. An urgent laparotomy is necessary if there is evidence of active bleeding or peritonitis at the initial examination, but these situations are uncommon. The main diagnostic challenge is to promptly and correctly identify lesions that require surgical repair. Diagnostic delay exceeding eight hours before surgical repair is associated with increased morbidity and probably with mortality. Because of this risk, the traditional therapeutic approach has been to operate on all patients with suspected bowel or mesenteric injury. However, this approach leads to a high rate of non-therapeutic laparotomy. A new approach of non-operative management (NOM) may be applicable to hemodynamically stable patients with no signs of perforation or peritonitis, and is being increasingly employed. This attitude has been described in several recent studies, and can be applied to nearly 40% of patients. However, there is no consensual agreement on which criteria or combination of clinical and radiological signs can insure the safety of NOM. When NOM is decided upon at the outset, very close monitoring is mandatory with repeated clinical examinations and interval computerized tomography (CT). Larger multicenter studies are needed to better define the selection criteria and modalities for NOM.

Dynamic biomechanical characterization of colon tissue according to anatomical factors.

INTRODUCTION: The aim of this study was to determine the mechanical response of colonic specimens retrieved from the entire human colon and placed under dynamic solicitation until the tissue ruptured. MATERIAL AND METHODS: Specimens were taken from 20 refrigerated cadavers from different locations of the colonic frame (ascending, transverse, descending and sigmoid colon) in two different directions (longitudinal and circumferential), with or without muscle strips (taenia coli). A total of 120 specimens were subjected to tensile tests, after preconditioning, at the speed of 1m/s. RESULTS: High-speed video analysis showed a bilayer injury process with an initial rupture of the serosa / external muscular layer followed by a second rupture of the inner layer consisting of the internal muscle / submucosa / mucosa. The mechanical response was biphasic, with a first point of initial damage followed by a complete rupture. The levels of stress and strain at the failure site were statistically greater in terms of circumferential stress (respectively 69±22% and 1.02±0.50MPa) than for longitudinal stress (respectively 55±32% and 0.70±0.34MPa). The difference between longitudinal and circumferential stress was not statistically significant (3.17±2.05MPa for longitudinal stress and 3.15±1.73MPa for circumferential stress). The location on colic frame significantly modified the mechanical response both longitudinally and circumferentially, whereas longitudinal taenia coli showed no mechanical influence. CONCLUSION: The mechanical response of the colon specimen under dynamic uniaxial solicitation showed a bilayer and biphasic injury process depending on the direction of solicitation and colic localization. Furthermore these results could be integrated into a numeric model reproducing abdominal trauma to better understand and prevent intestinal injuries.

[Video-assisted total proctocolectomy with ileoanal anastomosis]. / Coloproctectomie totale avec anastomose iléoanale vidéoassistée.

The indication for laparoscopy in digestive surgery has evolved with the development of the laparoscopic material as well its increasingly frequent practice in the medical community. Those complex operations such as restorative proctocolectomy require a high level of technical skill as well as a specifically designed operative approach. The study aim was to report our experience of the video-assisted approach to restorative proctocolectomy.

[Two stage videoassisted restorative proctocolectomy. Early experience of 12 cases]. / Coloproctectomie totale avec anastomose iléoanale en deux temps vidéoassistée. Expérience initiale de 12 cas.

AIM OF THE STUDY: This study reports our early experience in two-stage video assisted restorative proctocolectomy (RPC). PATIENTS AND METHODS: From May 1999 to May 2003, 12 video assisted RPCs were performed (mucosal ulcerative colitis: n = 11; familial adenomatous polyposis: n = 1). These patients were matched for age, gender, body mass index and indication for surgery, with 12 patients who underwent RPC by laparotomy (open group). RESULTS: Median operative time was significantly longer in the video assisted RPC group (400 min; range: 360-490) vs open group (300 min; range: 210-390) (P = 0.003). A conversion in midline laparotomy (under the umbilicus) was necessary in 3/12 patients (25%) in the video assisted RPC group. Return to bowel function and oral intake occurred two days earlier after video assisted RPC (respectively, P = 0.009 and P = 0.0001) but length of stay was not significantly shorter in this group. A complication occurred in 3/12 patients (25%) in both groups, which lead to a reoperation in one patient in the open group (ns). CONCLUSION: Two-stage videoassisted RPC is feasible at the cost of a lengthening of operative time, Nevertheless postoperative results after video assisted RPC are comparable to those obtained after RPC by laparotomy.

[Necrotizing enterocolitis during pregnancy in a woman operated on at six months of Hirschsprung's disease]. / Entérocolite nécrosante en fin de grossesse chez une femme opérée à l'âge de six mois d'une maladie de Hirschsprung.

Necrotizing enterocolitis is a rare and severe complication of Hischsprung's disease. Aggravation of unknown or undertreated Hischsprung's disease may be seen during pregnancy. To our knowledge, the following case is the first combining those two elements: necrotizing enterocolitis in a 20 years old women operated on of Hischsprung's disease when she was six months. The final diagnosis was made 24 hours later. Definitive treatment was a three-stage ileal pouch-anal anastomosis.

[Laparoscopic posterior fundoplication in gastroesophageal reflux: mid-term results]. / Fundoplicature postérieure coelioscopique pour reflux gastro-oesophagien: résultats à moyen terme.

STUDY AIM: The aim of this study was to report the mid-term results of the surgical management of gastroesophageal reflux disease (GERD) by laparoscopic posterior partial fundoplication (Toupet technique) in 100 patients, and to evaluate their post-operative quality of life. PATIENTS AND METHOD: Between November 1993 and January 2000, 100 patients were surgically treated for a medically refractory GERD. Laparoscopic posterior partial fundoplication was performed by the Toupet technique. In the postoperative period, the patients were asked to answer a questionnaire by telephone. The aim of this survey was three-fold: to identify clinical symptoms indicative of recurrence; to evaluate postoperative functional impairment; to assess the postoperative quality of life. pH monitoring was also proposed in asymptomatic patients at a minimum follow-up of two years, and in all patients with clinical symptoms of GERD recurrence. RESULTS: Six laparotomy conversions were necessary. The mean duration of follow-up was 18 months (range: 6 to 57 months). The rate of clinically diagnosed recurrence was 7.6%. Intermittent dysphagia was observed in 2.3% of cases. Postoperative digestive functional disorders were noted in 53% of patients without clinical recurrence, and 95.3% of them were satisfied or very satisfied with the results of surgery. CONCLUSION: Laparoscopic posterior partial fundoplication by the Toupet technique can satisfactorily treat GERD without mid-term recurrence in about 94% of cases. Patient satisfaction seems mainly to depend on the disappearance of clinical symptoms of GERD. It was found that postoperative functional disorders frequently occurred, but were well tolerated. Their etiology has not yet been determined, and it is considered that factors other than the surgical procedure may also play a role.

Blunt bowel and mesenteric injuries detected on CT scan: who is really eligible for surgery?

BACKGROUND: There is no consensually accepted approach to the management of blunt bowel and mesenteric injuries. Surgery is required urgently in the case of bowel perforation or haemodynamic instability, but several patients can be treated non-operatively. This study aimed to identify the risk factors for surgery in an initial assessment. METHODS: We retrospectively reviewed the medical charts and computed tomography (CT) scans of adult patients presenting with a blunt abdominal trauma to our centre between the years 2004 and 2011. We included only patients with a CT scan showing suspected injury to the mesentery or bowel. RESULTS: There were 43 patients (33 males and 10 females), with a mean Injury Severity Score (ISS) of 22. The most frequently suspected injuries based on a CT scan were mesenteric infiltrations in 40 (93 %) patients and bowel wall thickening in 22 (51 %) patients. Surgical therapy was required for 23 (54 %) patients. Four factors were independently associated with surgical treatment: a free-fluid peritoneal effusion without solid organ injury [adjusted odds ratio (OR) = 14.4, 95 % confidence interval (CI) [1.9-111]; p = 0.015], a beaded appearance of the mesenteric vessels (OR = 9 [1.3-63]; p = 0.027), female gender (OR = 14.2 [1.3-159]; p = 0.031) and ISS >15 (OR = 6.9 [1.1-44]; p = 0.041). Surgery was prescribed immediately for 11 (26 %) patients and with delay, after the failure of initially conservative treatment, for 12 (28 %) patients. The presence of a free-fluid peritoneal effusion without solid organ injury was also an independent risk factor for delayed surgery (OR = 9.8 [1-95]; p = 0.048). CONCLUSIONS: In blunt abdominal trauma, the association of a bowel and/or mesenteric injury with a peritoneal effusion without solid organ injury on an initial CT scan should raise the suspicion of an injury requiring surgical treatment. Additionally, this finding should lead to a clinical discussion of the benefit of explorative laparotomy to prevent delayed surgery. However, these findings need validation by larger studies.

[Stab wounds in emergency department]. / Les plaies par arme blanche et leur prise en charge aux urgences.

Stab wounds represent the most common cause of penetrating wounds, occurring mainly in case of aggression or suicide attempt. Clinical severity depends on the superficial or penetrating aspect of the wound, its location and damaged organs. Medical management must be known because the vital risk is involved in penetrating wounds. Hemodynamically unstable patients should be operated without delay after performing a chest X-ray and ultrasound Focus assisted sonography for trauma (FAST) to guide the surgery. In the stable patients, the general clinical examination, exploration of the wound and medical imaging detect injuries requiring surgical management. Stab penetrating wounds require close and rapid collaboration between medical teams, tailored to the institution's resources.

[Risks related to tobacco use in general and intestinal surgery]. / Risques liés au tabagisme en chirurgie générale et digestive.

Peri-operative smoking history is an important risk factor, which is often under-appreciated by surgeons. In the first place, tobacco use predisposes patients to specific pathologies, which may require surgical intervention. Secondarily, smoking has been shown to increase surgical risks of mortality, morbidity and length of hospital stay. Of particular importance in general surgery is the increased risk of anastomotic leak with fistula formation, of deep infections, and of abdominal wall complications (infection and ventral hernia). If the patient can stop smoking prior to surgery, there is a concomitant decrease in post-operative complications. Surgeons should be familiar with the pharmacologic and behavioral interventions, which may help the patient with smoking cessation and should not hesitate to defer elective surgery for four to eight weeks so that the patient may have the full benefit of smoking cessation.

Contribution of spindle reflexes to post-inspiratory activity in the canine external intercostal muscles.

1. The external intercostal muscles have greater post-inspiratory activity than the parasternal intercostal muscles and are more abundantly supplied with muscle spindles. In the present study, the hypothesis was tested that spindle afferent inputs play a major role in determining this activity. 2. The electrical activity of the external and parasternal intercostal muscles in the rostral interspaces was recorded in anaesthetized spontaneously breathing dogs, and the ribs were manipulated so as to alter their normal caudal displacement and the normal lengthening of the muscles in early expiration. 3. Post-inspiratory activity in the external intercostal muscles showed a reflex decrease when the caudal motion of the ribs and the lengthening of the muscles was impeded, and it showed a reflex increase when the rate of caudal rib motion and muscle lengthening was increased. In contrast, the small post-inspiratory activity in the parasternal intercostal muscles remained unchanged. 4. When the two ribs making up the interspace investigated were locked to keep muscle length constant, post-inspiratory activity in the external intercostal muscles was reduced and no longer responded to cranial rib manipulation. 5. These observations confirm that afferent inputs from muscle receptors, presumably muscle spindles, are a primary determinant of post-inspiratory activity in the canine external intercostal muscles. In anaesthetized animals, the contribution of central control mechanisms to this activity is small.

Post-operative faecal continence in patients with ulcerative colitis after ileo-anal anastomosis with preservation of the transitional zone: a report from a low-incidence region.

The aim of this prospective study was to analyse post-operative faecal continence by carrying out a manometric and clinical follow-up on ten patients previously suffering from ulcerative colitis, who underwent total proctocolectomy and double-stapled ileo-anal anastomosis with preservation of the transitional zone. An annual histological analysis of the transitional zone was performed post-operatively. A 13% reduction in the length of the high-pressure zone of the anal canal (P = 0.04) was observed without any significant change in the resting anal pressure or the maximal squeeze pressures. Fifty percent of the patients showed histological signs of inflammation, without any clinical manifestations. The median number of bowel movements was 4 per day and 1 per night, and only 1 patient had occasional nocturnal soiling (less than once a week). On being questioned, 9 patients replied that they rated their continence as good or very good and 1 patient, as reasonable. These findings show that ileo-anal anastomosis, without mucosal resection preserves the normal resting anal pressure and anal function despite the reduction in the length of the high pressure zone it involves.

Follow-up of selective endoscopic ultrasonography and/or endoscopic retrograde cholangiography prior to laparoscopic cholecystectomy: a prospective study of 300 patients.

BACKGROUND AND STUDY AIMS: This prospective study evaluated the selective use of endoscopic retrograde cholangiography (ERC) and endoscopic ultrasonography (EUS) in the context of laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: Between 1993 and 1998, LC for symptomatic gallstones was indicated in 300 consecutive patients. In order to diagnose and treat choledocholithiasis preoperatively, we performed, on the basis of preoperative criteria, ERC in "high-risk" patients and EUS in "intermediate-risk" patients. Choledocholithiasis was treated by preoperative biliary endoscopic sphincterotomy (BES). LC was performed either after the endoscopic procedure or directly in "low-risk" patients. RESULTS: A total of 104 patients (35%) had 118 preoperative procedures: a) EUS (n = 68; feasibility 100%): choledocholithiasis was observed in 14/68 patients (21%); b) ERC (n = 50; feasibility 94%): 36 ERC were indicated on on preoperative criteria, and 14 on the basis of EUS results. Choledocholithiasis was found in 41/ 50 patients (82%) (13/14 patients with positive EUS), 19% of "intermediate-risk" patients, and 78% of "high-risk" patients; ERC failed in three patients who had no choledocholithiasis on subsequent intraoperative cholangiography (IOC). Clearance of the common bile duct (CBD) was achieved after BES in 41/41 patients. There was no mortality; complications occurred in 4/ 300 patients (1%). No retained stones were found in patients of any of the three groups, after a mean follow-up of 32 months. CONCLUSIONS: Combined endoscopic and laparoscopie management of cholecystolithiasis and choledocholithiasis is a viable option and is optimized by the use of EUS.

A western surgical experience of peripheral cholangiocarcinoma.

The aim of this retrospective study was to analyse outcome in 31 European patients operated on for peripheral cholangiocarcinoma between 1988 and 1995 (hilar cholangiocarcinoma was excluded). Before 1992, in addition to conventional resection, patients with irresectable tumour and with no extrahepatic metastasis underwent total hepatectomy with liver transplantation. Mild abdominal pain was the most frequent presenting clinical sign (11 of 31 patients) and jaundice was present in only four patients. Preoperative histological findings were available for 20 patients but the diagnosis was correct in only eight of these. Nineteen patients had curative surgery: 17 underwent conventional resection and two had total hepatectomy with liver transplantation. Major hepatectomy was performed in 12 of 17 cases, extended to the caudate lobe in five, to the bile duct confluence in four and to the retrohepatic vena cava in one. Postoperative mortality and morbidity rates were three and seven of 19 patients respectively, median survival was 15 months, and actuarial 1-, 2- and 5-year survival rates were 67, 40 and 32 per cent respectively. Twelve patients had only exploratory laparotomy because of the presence of extrahepatic metastasis or irresectable tumour. The invasive nature of peripheral cholangiocarcinoma can explain the limited number of resectable cases and the particularly unfavourable prognosis. Total hepatectomy does not provide survival benefit. Conventional surgery remains the only effective treatment, even for patients with advanced stage tumours.