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Introduction Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months. Methods A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm2, scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months. Results Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery. Conclusion After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations. Trial registration Registered on clinicaltrials.gov (NCT02720042), March 25, 2016.

Objective Medical Crew Resource Management (CRM) training courses are designed to increase patient safety by reducing the effects of human errors. These training courses are most popular in surgery and a wide range of medical CRM training courses for surgical teams is now available. However, the effects of these CRM training courses on patient outcomes are inconclusive. Although surgical teams feel the need to be trained in team collaboration skills, they are often puzzled about what criteria to apply when choosing a medical CRM training course. This study aimed to compare CRM training courses on didactic components and simulation-exercises to explore if these courses are interchangeable. Methods In this qualitative study, semi-structured interviews were conducted among 10 main CRM training providers of surgical teams in the Netherlands. Results Although a large variety was found in the content of CRM training courses, the most substantial differences were found in the simulation-exercises. Nine out of 10 trainers stated that standard simulation-exercises would be a step forward to ensure quality in CRM trainings. According to the trainers, the implementation of medical CRM can reduce human errors and as a result, preventable patient complications. They suggested a quality standard for CRM trainers in the medical field to ensure the quality of medical team training as a way to reach this. Conclusions Medical CRM training courses are diverse and noninterchangeable. Trainers expect that if CRM becomes part of surgical training and is embedded in operating theatre culture, it could be of great value for patients and professionals.

Background: Repair of large ventral hernias with loss of domain can be facilitated by preoperative Botulinum toxin A (BTA) injections and preoperative progressive pneumoperitoneum (PPP). The aim of this study is to evaluate the outcomes of ventral hernioplasty using a standardized algorithm, including component separation techniques, preoperative BTA and PPP. Methods: All patients between June 2014 and August 2018 with giant hernias (either primary or incisional) of more than 12 cm width were treated according to a previously developed standardized algorithm. Retrospective data analysis from a prospectively collected dataset was performed. The primary outcome was closure of the anterior fascia. Secondary outcomes included complications related to the preoperative treatment, postoperative complications, and recurrences. Results: Twenty-three patients were included. Median age was 65 years (range 28–77) and median BMI was 31.4 (range 22.7–38.0 kg/m2). The median loss of domain was 29% (range 12–226%). For the primary and secondary endpoints, 22 patients were analyzed. Primary closure of the anterior fascia was possible in 82% of all patients. After a median follow-up of 19.5 months (range 10–60 months), 3 patients (14%) developed a hernia recurrence and 16 patients (73%) developed 23 surgical site occurrences, most of which were surgical site infections (54.5%). Conclusion: Our algorithm using both anterior or posterior component separation, together with preoperative BTA injections and PPP, achieved an acceptable fascial closure rate. Further studies are needed to explore the individual potential of BTA injections and PPP, and to research whether these methods can prevent the need for component separation, as postoperative wound morbidity remains high in our study.

Background Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non-surgical management (antibiotics with or without percutaneous drainage (PCD)). The aim was to assess outcomes of non-surgical treatment and to identify risk factors for adverse outcomes. Methods Patients with a first episode of CT-diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non-surgically. Baseline characteristics, short-term (within 30 days) and long-term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no-PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery. Results Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow-up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74·3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short-term treatment failure (Hinchey I: 22·3 versus 33 per cent, P = 0·359; Hinchey II: 25·9 versus 36 per cent, P = 0·149) or emergency surgery (Hinchey I: 5·1 versus 6 per cent, P = 0·693; Hinchey II: 10·4 versus 15 per cent, P = 0·117), but significantly more complications were found in patients with Hinchey II disease undergoing PCD (12 versus 3·7 per cent; P = 0·032). Multivariable analyses showed that treatment strategy (PCD versus no PCD) was not independently associated with short-term treatment failure (odds ratio (OR) 1·47, 95 per cent c.i. 0·81 to 2·68), emergency surgery (OR 1·29, 0·56 to 2·99) or long-term surgery (hazard ratio 1·08, 95 per cent c.i. 0·69 to 1·69). Abscesses of at least 3 cm in diameter were associated with short-term treatment failure (OR 2·05, 1·09 to 3·86), and abscesses of 5 cm or larger with the need for surgery during short-term follow-up (OR 2·96, 1·03 to 8·13). Conclusion The choice between PCD with antibiotics or antibiotics alone as initial non-surgical treatment of Hinchey Ib and II diverticulitis does not seem to influence outcomes.

Incisional hernia is a frequent complication after abdominal surgery. A risk factor for incisional hernia, related to body composition, is obesity. Poor skeletal muscle mass might also be a risk factor, as it may result in weakness of the abdominal wall. However, it remains unknown if sarcopenia (i.e. low skeletal muscle mass) is a risk factor for incisional hernia. Therefore, this study aims to investigate whether a relation between sarcopenia and incisional hernia exists. Patients from the STITCH trial, who underwent elective midline laparotomy, were included. Computed tomography examinations performed within 3 months preoperatively were used to measure the skeletal muscle index (SMI; cm2/m2). Primarily, SMI measured continuously, sarcopenia based on previously described cut-off values for the SMI, and sarcopenia as the lowest gender-specific SMI quartile were assessed as measures to predict incisional hernia occurrence. Secondary, the association between these three measures and post-operative complications was investigated. In total, 283 patients (45.2% male; mean age 63.7 years; mean BMI 25.36 kg/m2) were included, of whom 52 (18%) developed an incisional hernia. Mean SMI was 44.23 cm2/m2 (SD 7.77). The Nagelkerke value for the three measures of sarcopenia was about 0.020 (2.0%) for incisional hernia development. Logistic regressions with the three measures of sarcopenia did not show any predictive value of the model (area under the curve (AUC) of 0.67 for incisional hernia; 0.69 for post-operative complications). In this study, sarcopenia does not seem to be a risk factor for the development of an incisional hernia.

Purpose: Ventral hernia repair is one of the most frequently performed surgical procedures, though recurrences are common. Recurrence can be caused by impaired collagen formation or maturation; hence, patients with Ehlers-Danlos syndrome (EDS) are potentially at increased risk for hernia recurrence. EDS causes altered collagen metabolism, though little is known about the influence of EDS on ventral hernioplasty outcomes. This study aims to analyze these patients to report complication rates, recurrence rates, and, if possible, to give recommendations for surgical intervention. Methods: A retrospective analysis between January 2000 and January 2017 was performed in a university hospital Belgium (UZ Ghent). Data on baseline characteristics, primary surgery, and hernias were extracted from patients' medical charts. Noted endpoints were postoperative complications and recurrences. Results: Fourteen patients (50% males) were included. Ten (71%) had an incisional hernia and four (29%) had a primary ventral hernia. Median age was 45 years (IQR 37.75-52.75), median BMI was 24.82 (IQR 22.43-26.87). Four patients (29%) smoked, one patient (7.1%) had diabetes mellitus, and five patients (36%) had an aneurysm of the abdominal aorta. All patients underwent elective open hernioplasty with mesh reinforcement. Three patients (21%) had a postoperative complication (two infections, one seroma). Recurrence rate was 7.1% (one patient). Conclusions: This series describes 14 patients with a median follow-up of 50 months and a recurrence rate of 7.1%. The low recurrence rate could be explained by the use of large meshes that reinforce the entire midline to compensate for the reduced collagen strength in EDS patients.

Background Laparoscopic peritoneal lavage is an alternative to sigmoid resection in selected patients presenting with purulent peritonitis from perforated diverticulitis. Although recent trials have lacked superiority for lavage in terms of morbidity, mortality was not compromised, and beneficial secondary outcomes were shown. These included shorter duration of surgery, less stoma formation and less surgical reintervention (including stoma reversal) for laparoscopic lavage versus sigmoid resection respectively. The cost analysis of laparoscopic lavage for perforated diverticulitis in the Ladies RCT was assessed in the present study. Methods This study involved an economic evaluation of the randomized LOLA (LaparOscopic LAvage) arm of the Ladies trial (comparing laparoscopic lavage with sigmoid resection in patients with purulent peritonitis due to perforated diverticulitis). The actual resource use per individual patient was documented prospectively and analysed (according to intention‐to‐treat) for up to 1 year after randomization. Results Eighty‐eight patients were randomized to either laparoscopic lavage (46) or sigmoid resection (42). The total medical costs for lavage were lower (mean difference € − 3512, 95 per cent bias‐corrected and accelerated c.i. −16 020 to 8149). Surgical reintervention increased costs in the lavage group, whereas stoma reversal increased costs in the sigmoid resection group. Differences in favour of laparoscopy were robust when costs were varied by ±20 per cent in a sensitivity analysis (mean cost difference € − 2509 to −4438). Conclusion Laparoscopic lavage for perforated diverticulitis is more cost‐effective than sigmoid resection., Further evidence of lavage superiority

Purpose After closure of laparotomies, sutures may pull through tissue due to too high intra-abdominal pressure or suture tension, resulting in burst abdomen and incisional hernia. The objective of this study was to measure the suture tension in small and large bites with a new suture material. Methods Closure of the linea alba was performed with small bites (i.e., 5 mm between two consecutive stitches and 5 mm distance from the incision) and large bites (i.e., 10 mm × 10 mm) with Duramesh™ size 0 (2 mm) and PDS II 2-0 in 24 experiments on six porcine abdominal walls. The abdominal wall was fixated on an artificial computer-controlled insufflatable abdomen, known as the ‘AbdoMan’. A custom-made suture tension sensor was placed in the middle of the incision. Results The suture tension was significantly lower with the small bites technique and Duramesh™ when compared with large bites (small bites 0.12 N (IQR 0.07–0.19) vs. large bites 0.57 N (IQR 0.23–0.92), p p Conclusion Closure of the abdominal wall with the small bites technique and Duramesh™ was more efficient in dividing suture tension across the incision when compared to large bites. However, suture tension compared to a conventional suture material was not significantly different, contradicting an advantage of the new suture material in the prevention of burst abdomen and incisional hernia during the acute, postoperative phase.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool. ispartof: COLORECTAL DISEASE vol:22 issue:1 pages:36-45 ispartof: location:England status: published

Cytokine storm described in patients after allogeneic haematopoietic stem cell transplantation (alloHSCT) is associated with the appearance of CD14 + HLADR - in the blood.To study the role of CD14 + HLADR - cells 223 patients after alloHSCT followed from 1 month to 15 years. The methods used included flow cytometry for blood cells profiling, nucleic acid tests for viral reactivation, and physician care according to the Polish and international guidelines.We found that CD14 + HLADR - peak values determined during the first 60 post-transplant days were higher in the patients who died than in those who survived in this time interval (mean ± SEM: 3.78 ± 0.67% vs 2.38 ± 0.65%, p 0.001). Receiver operating characteristic (ROC) analysis showed that CD14 + HLADR - cells level in the blood at cut-off point at 0.71% discriminated the patients as to survival; the patients above the threshold had poorer survival (Kaplan-Meier curve covering 15-year observation) than those below (0.19 vs 0.46, p 0.001). Infections prevailed other causes of death in the high blood CD14 + HLADR - group (0.61 vs 0.38, p = 0.057). ROC analysis defined the CD4+ blood level at 17.70% as not significantly associated with survival. Multivariate analysis revealed that CD14 + HLADR - cells (HR = 3.47, p 0.001) and the presence of acute graft-versus-host disease (aGvHD) grade ≥ 3 (HR = 3.82, p = 0.005) adversely impacted the survival.CD14 + HLADR - cells can serve as a biomarker for the risk of fatal complications frequently associated with infections.

Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects the acute response of macrophages to biomaterials in vitro and whether this response is associated with biomarkers in blood. CD14(+) monocytes were isolated from blood from obese and age and gender matched lean persons. Monocyte subsets were determined based on CD14 and CD16 on their surface. C-reactive protein (CRP) was measured in peripheral blood. The response of monocyte-derived macrophages to polypropylene (PP), polylactic acid (PLA), polyethylene terephthalate (PET) mono filament, and PET-multifilament (mPET) in culture was based on cytokine production. More IL-6 (for PET), less CCL18 (all materials) and IL-1ra (for PLA) was produced by macrophages from obese patients than lean subjects. Body mass index, serum CRP and to a lesser extend percentages of monocyte subtypes correlated with IL-6, TNF alpha, CCL18, and IL-1ra production. Taken together, monocyte-derived macrophages of obese patients respond more pro-inflammatory and less anti-inflammatory to biomaterials than macrophages from lean subjects, depending on the material. These results are a step towards personalized medicine for the development of a model or even a blood test to decide which biomaterial might be suitable for each patient. (C) 2016 Elsevier Ltd. All rights reserved.

In our previous study (Jaskula et al., Blood 2017 130:1420) we reported that the number of CNVs within the KANSL1 gene was associated with the phenotype of AML. In the present study we looked at the presence of CNV across the whole genome. One hundred and twenty seven AML patients (diagnosed according to the FAB/WHO criteria, F/M=62/65, age median: 57, range: 21 - 84 years) were included to the present study. The patients were genetically analysed including GTG karyotyping and/or FISH for X or Y deletion, inv (3), -5/5q-, -7/7q-,+8, MLL, RUNX1, PML/RARA or RARA, inv(16). In all patients the microarray analysis of the bone marrow cells having blasts cells (median value 56%) at diagnosis Agilent - Catalog Agilent Cancer CGH+SNP 180K (74 patients) or Roche - WG Catalog NimbleGene 12x270K (53 patients) microarrays were employed and the results were analysed with the use the Partek software employing the Partek Hidden Markov Model (HMM) and segmentation algorithms. Results: The number of CNV in M0 AML marrow cells was significantly lower (median: 0 aberration), as compared to secondary to MDS AML (median: 4.5 aberrations, p=0.006). Patients with AML subtypes from M1 to M6 had higher number of CNV amplifications (median: 2) as compared to the patients with minimally differentiated blasts (M0, median: 0 amplifications, p=0.030). Knowing that (i) changes in the chromatin structure may be associated with the CNV prevalence within the genome (Gheldof et al., PLoS One. 2013 Nov 12;8(11):e79973) and (ii) the aberrant expression of CD19 in AML blasts results from the chromatin structure variations (Walter et al., Oncogene. 2010 May 20;29(20):2927-37) we looked at the presence of association between the numbers of CNV and the presence of the aberrant CD19 expression in the leukemic blasts. It appeared that 11 AML patients having aberrant expression of CD19 (within whom 4 had t(8:21)) had more frequently CNV deletions than those lacking this aberrant expression (median: 2 vs 1 deletions, p=0.018, HMM algorithm). Having the survival curves of the patients plotted accordingly to the high and low numbers of CNV, the situation is more complex and shows that: the patients having higher numbers of CNV aberrations (exceeding the mean of the whole group +SD) enjoyed better survival (20% vs 11%, p=0.090) when segmentation algorithm was employed. HMM analysis also suggested that the higher values of CNV (amplifications, exceeding the mean of the whole group +SD) was associated with better 5-year survival as compared to those with low numbers (42% vs 20%, ns). The aberrant expression of CD19 analysis was associated with higher numbers of deletions (see above) and with better 5-year survival than those lacking this aberrant expression (45% vs 20%, p=0.064). In conclusion, the prevalence of CNV within the genome shapes the phenotype of the leukemia and facilitates the survival. Disclosures No relevant conflicts of interest to declare.

Incisional hernia is a commonly occurring long-term complication following laparotomies. Risk factors for the development of incisional hernia may be divided into patient related risk factors and surgery related risk factors. Optimizing surgical techniques and used materials to close abdominal wall incisions hold the potential of preventing the development of incisional hernia, reducing postoperative disability and saving costs in the healthcare system. The surgical techniques and used suture materials for closing abdominal wall incisions are important determinative factors in preventing incisional hernia and will be discussed in this chapter. Furthermore, the placement of a prophylactic mesh in order to prevent an incisional hernia in high risk patients and optimization of patients pre-, peri- and postoperatively will be discussed.

BACKGROUND: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients. METHODS: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery. CONCLUSION: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients. TRIAL REGISTRATION: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042 . ispartof: BMC SURGERY vol:18 issue:1 ispartof: location:England status: published

We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia. The patients (i) responded to the treatment with cessation of blasts which lasted 1, 17 and 42+ months, (ii) developed skin lesions with CD3+ cell invasion of the epidermis, (iii) had marrow infiltrated with CD8+ lymphocytes which co-expressed PD-1 (programmed cell death protein 1 receptor, CD279) in higher proportions than those in the blood (163±32 x103 cells/μl vs 38±8 x103 cells/μl, p

Incisional hernia (IH) is the most frequent complication after abdominal surgery. The diagnostic modality, observer, definition, and diagnostic protocol used for the diagnosis of IH potentially influence the reported prevalence. The objective of this systematic review is to evaluate the diagnostic accuracy of different modalities used to identify IH. Embase, MEDLINE OvidSP, Web of Science, Google Scholar, and Cochrane databases were searched to identify studies diagnosing IH. Studies comparing the IH detection rate of two different diagnostic modalities or inter-observer variability of one modality were included. Quality assessment of studies was done by Cochrane Collaboration’s tool. Article selection and data collection were performed independently by two researchers. PROSPERO registration: CRD42017062307. Fifteen studies representing a total of 2986 patients were included. Inter-observer variation for CT-scan ranged from 11.2 to 69% (n = 678). Disagreement between ultrasound and CT-scan ranged between 6.6 and 17% (n = 221). Ten studies compared physical examination to CT-scan or ultrasound. Disagreement between physical examination and imaging ranged between 7.6 and 39% (n = 1602). Between 15 and 58% of IHs were solely detected by imaging (n = 483). Relative increase in IH prevalence for imaging compared to physical examination ranged from 0.92 to 2.4 (n = 1922). Ultrasound or CT-scan will result in substantial additional IH diagnosis. Lack of consensus regarding the definition of IH might contribute to the disagreement rates. Both the observer and diagnostic modality used could be additional factors explaining variability in IH prevalence and should be reported in IH research.

Background The use of synthetic mesh to repair a potentially contaminated incisional hernia may lead to higher failure rates. A biological mesh might be considered, but little is known about long-term results. Both biological and synthetic meshes were investigated in an experimental model of peritonitis to assess their characteristics in vivo. Methods Male Wistar rats were randomized into five groups and peritonitis was induced. A mesh was implanted after 24 h. Five meshes were investigated: Permacol™ (cross-linked collagen), Strattice™ (non-cross-linked collagen), XCM Biologic® (non-cross-linked collagen), Omyra® Mesh (condensed polytetrafluoroethylene) and Parietene™ (polypropylene). The rats were killed after either 30, 90 or 180 days. Incorporation and shrinkage of the mesh, adhesion coverage, strength of adhesions and histology were analysed. Results Of 135 rats randomized, 18 died from peritonitis. Some 180 days after implantation, both XCM Biologic® and Permacol™ had significantly better incorporation than Strattice™ (P = 0·003 and P = 0·009 respectively). Strattice™ had significantly fewer adhesions than XCM Biologic® (P = 0·001) and Permacol™ (P = 0·020). Thirty days after implantation, Permacol™ had significantly stronger adhesions than Strattice™ (P < 0·001). Shrinkage was most prominent in XCM Biologic®, but no significant difference was found compared with the other meshes. Histological analysis revealed marked differences in foreign body response among all meshes. Conclusion This experimental study suggested that XCM Biologic® was superior in terms of incorporation, macroscopic mesh infection, and histological parameters such as collagen deposition and neovascularization. There must be sufficient overlap of mesh during placement, as XCM Biologic® showed a high rate of shrinkage. Surgical relevanceThe use of synthetic mesh to repair a potentially contaminated incisional hernia is not supported unequivocally, and may lead to a higher failure rate. A biological mesh might be considered as an alternative. There are few long-term studies, as these meshes are expensive and rarely used.This study evaluated the use of biological mesh in a contaminated environment, and investigated whether there is an ideal mesh. A new non-cross-linked biological mesh (XCM Biologic®) was evaluated in this experiment.The new non-cross-linked biological mesh XCM Biologic® performed best and may be useful in patients with a potentially contaminated incisional hernia.

Among cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT), some are sensitive to natural killer (NK) cell reactivity, described as the “missing self” recognition effect. However, this model disregarded the NK cell licensing effect, which highly increases the NK cell reactivity against tumor and is dependent on the coexpression of inhibitory killer cell immunoglobulin-like receptor (iKIR) and its corresponding HLA Class I ligand. We assessed clinical data, HLA and donor iKIR genotyping in 283 patients with myelo- and lymphoproliferative malignancies who underwent HSCT from unrelated donors. We found dramatically reduced overall survival (OS), progression free survival (PFS), and time to progression (TTP) among patients with malignant diseases with the lack of HLA ligand cognate with this iKIR involved in NK cell licensing in corresponding donor (events 83.3% vs. 39.8%, P = 0.0010; 91.6% vs. 47.7%, P = 0.00010; and 30.0% vs. 17.3%, P = 0.013, for OS, PFS, and TTP, respectively). The extremely adverse PFS have withstand the correction when patient group was restricted to HLA mismatched donor-recipient pairs. The incidence of aGvHD was comparable in two groups of patients. In malignant patients after HSCT the missing HLA ligand for iKIR involved in NK cell licensing in corresponding donor (“missing licensing proof”) induced extremely adverse survival of the patients due to the progression of malignancy and not to the aGvHD. Avoiding the selection of HSCT donors with the “missing licensing proof” in the malignant patient is strongly advisable.Am. J. Hematol. 89:E176–E183, 2014. © 2014 Wiley Periodicals, Inc.

A Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) case was maintained in remission with the use of chemo-immunotherapy. The latter involved sibling bone marrow transplant (BMT) (three procedures) followed by intravenous (IV) donor lymphocyte infusion (DLI). The third relapse responded to routine chemotherapy and again DLI was employed. During hematological and molecular remission verified at the level of iliac crest aspiration, extra-medullary relapse in the bones was apparent. A novel procedure of donor lymphocyte injection to the bone leukemic lesions was developed and employed. A dose of 10(6) donor lymphocytes/kg body weight (BW) of the recipient were each time injected to the plane of the right and left tibia, the head of the humerus, and the calcaneus, which resulted in healing of the destructive process. In consequence of this novel approach, in addition to the healing of bone lesions, an accumulation of cytotoxic activated T-cells in the marrow was documented, which was mirrored by an increase in the number of transcripts for interferon (IFN)-γ, interleukin (IL)-17, as well as RORγt. The local administration of DLI directly to the leukemic lesions requires a lower dose that diminishes the toxicity due to the general immune system activation.

Aim The study aimed to analyse the currently available national and international guidelines for areas of consensus and contrasting recommendations in the treatment of diverticulitis and thereby to design questions for future research. Method MEDLINE, EMBASE and PubMed were systematically searched for guidelines on diverticular disease and diverticulitis. Inclusion was confined to papers in English and those

_Dear Editor,_ We thank Dr Wee for his interest in our recently published article. Dr Wee indicated some ambiguities and provided recommendations regarding the methodology and outcomes of our study. We would like to address these issues. First, with regard to the statistical methods used, cumulative data were used to derive percentages of detected stoma site incisional hernias (SSIHs) and the associated median follow-up periods were derived by calculating the median and interquartile range of the available information on reported median study followup since closure (as given in Table 4). In addition, ...

Bone marrow constitutes a reservoir of progenitor cells which, being at different stages of differentiation, stay dormant until mobilised by signals coming from outside. It was postulated in the early 2000s that endothelial progenitor cells may leave the marrow under the force exerted by the hypoxia

Abscess formation and perforation are complications of acute appendicitis that lead to localized or generalized peritonitis. The long-term implications of complicated appendectomy remain largely unknown. In the present study, it was investigated whether patients with complicated appendicitis experienced more abdominal complaints after long-term follow-up when compared to uncomplicated cases. In addition, the influence of operation technique (open versus laparoscopic) was studied. A retrospective analysis of 1,481 appendectomies for acute appendicitis was performed in two centers from January 2000 until January 2006. Demographic data, operative reports, intraoperatively adhesions and complications, abdominal pain, and satisfaction were monitored. In total, 1,433 patients were invited to fill out a questionnaire with a median follow-up of 7.1 years. Questionnaires of 526 (37 %) patients were suitable for analysis. Perforation, abdominal abscesses, or adhesions at initial operation did not result in more abdominal complaints when compared to appendectomy for uncomplicated acute appendicitis. Additionally, no significant differences in abdominal complaints were seen between laparoscopic and open techniques. In conclusion, the results of our study show that after follow-up of 7 years, the incidence of abdominal complaints was not influenced by operative technique or whether acute appendicitis was complicated or not. This finding does not support a causative role for adhesions with regard to chronic abdominal complaints. Our data enables surgeons to inform their patients about the long-term results of appendectomy, whether it was complicated or not.

The role of local ischaemia in the pathogenesis of colorectal anastomotic leakage (AL) is not known. This study investigates the role of local ischaemia caused by sutures in an experimental colonic anastomosis model. 36 mice were assigned to three types of anastomosis, all using running sutures; in the first group 5 stitches were used, in the second group 12 stitches were used, and in the third group at least 30 stitches were used. After 7 days the mice were re-operated, signs of AL were scored, and coronal sections of the anastomosis were histologically analyzed. The distribution of weight was not significantly different between the three groups. Mortality was 44% and not significantly different between the groups (group 1: 5/12, group 2: 4/12, and group 3: 7/12, p = 0.72). Faecal and purulent AL were observed in 6 animals in group 1, 2 in group 2, and 3 in group 3 (group 1: 50%, group 2: 17%, and group 3: 25%, p = 0.19). The distance between the two colonic edges (group 1: 0.51 mu m, group 2: 1.34 mu m, and group 3: 0.53 mu m, p = 0.18), the diameter of the lumen at the site of the anastomosis (group 1: 2.92 mu m, group 2: 4.06 mu m, and group 3: 3.2 mu m, p = 0.9), and the largest diameter of the lumen proximally to the anastomosis (group 1: 2.05 mu m, group 2: 3.1 mu m, and group 3: 2.6 mu m, p = 0.25) were not different between the groups. Histological parameters of wound healing were not significantly different for the three groups. In this study no macroscopic and microscopic differences were observed between colon anastomosis with 5 stitches versus 12 and >30 stitches. This might indicate that local ischaemia does not negatively influence colonic wound healing. Copyright (C) 2013 S. Karger AG, Basel

Patients with liver cirrhosis scheduled for liver transplantation often present with a concurrent umbilical hernia. Optimal management of these patients is not clear. The objective of this study was to compare the outcomes of patients who underwent umbilical hernia correction during liver transplantation through a separate infra-umbilical incision with those who underwent correction through the same incision used to perform the liver transplantation.In the period between 1990 and 2011, all 27 patients with umbilical hernia and liver cirrhosis who underwent hernia correction during liver transplantation were identified in our hospital database. In 17 cases, umbilical hernia repair was performed through a separate infra-umbilical incision (separate incision group) and 10 were corrected from within the abdominal cavity without a separate incision (same incision group). Six patients died during follow-up; no deaths were attributable to intraoperative umbilical hernia repair. All 21 patients who were alive visited the outpatient clinic to detect recurrent umbilical hernia.One recurrent umbilical hernia was diagnosed in the separate incision group (6 %) and four (40 %) in the same incision group (p = 0.047). Two patients in the same incision group required repair of the recurrent umbilical hernia; one of whom underwent emergency surgery for bowel incarceration. The one recurrent hernia in the separate incision group was corrected electively.In the event of liver transplantation, umbilical hernia repair through a separate infra-umbilical incision is preferred over correction through the same incision used to perform the transplantation.

Complications after thoracic surgery have well been established, pain being the most prominent. Intercostal nerves are mixed type nerves combining motor and sensory functions. This notion is not consistent with the incidence of PTPS compared to the incidence of muscle paresis or paralysis. We would hypothesize that abdominal wall paresis or paralysis is underdiagnosed. In our hospital, three patients developed abdominal wall paralysis after thoracic surgery and consequent nerve damage. Their cases are discussed, and a review of the literature was conducted concerning (intercostal) nerve damage on a cellular level, the anatomy of the intercostal nerve, prevention of intercostal nerve damage and surgical techniques. A cellular cascade known as Wallerian degeneration and regeneration determine whether a damaged nerve can function again. The recovery of the nerve is highly dependent on the correct function of activated Schwann cells and macrophages and is related to the amount of damage that has taken place. The anatomy of the intercostal nerve makes it susceptible to injury. Retractor placement during open thoracic surgery has shown to effect compression injury and induced mechanical deformation and damage. Given the known factors of pathophysiology and anatomy, a number of preventive measures have been tested to reduce intercostal nerve damage. Several techniques have been proposed, but the most used technique, the video-assisted thoracic surgery, has been the most effective in reducing nerve damage. Abdominal wall paralysis is an underdiagnosed complication after thoracic surgery. The amount of stress on the intercostal nerves could be reduced with less invasive techniques such as the VATS technique.

Introduction: Technical failure of sutured or stapled anastomoses may lead to anastomotic leakage, which is one of the most important complications after colorectal surgery. Cyanoacrylate glue (CA) provides strong mechanical attachment, making it a good candidate for suture reinforcement. This study aimed to demonstrate that CA is the most important factor in the strength of a sealed colorectal anastomosis, in both normal and insufficient anastomoses. Methods: Ex vivo porcine colorectal segments were resected. A 1-layer continuous anastomosis or an insufficient 6-interrupted-suture anastomosis was created, and the baseline anastomotic bursting pressure (ABP) was measured. The primary anastomosis was then reinforced either by CA or with 4 additional interrupted sutures, further inverting the anastomosis. After reinforcement a second ABP test was performed. Results: Thirty-two segments were used. Reinforcing the anastomosis by CA significantly increased ABP in both normal and insufficient anastomoses when compared to the primary anastomosis (p < 0.05 for all groups); no significant difference in ABP was found between normal and insufficient anastomosis groups after CA reinforcement. Anastomotic reinforcement with CA was not inferior to the reinforcement with sutures in both normal and insufficient anastomoses, and had significantly fewer ABP variances in normal anastomosis groups (p = 0.042). Conclusion: Reinforcing a colorectal anastomosis with CA increases its mechanical strength in both normal and technically insufficient situations, which may contribute to the reduction of anastomotic leakage. CA is promising for anastomotic reinforcement based on mechanical improvement of the anastomosis, and in vivo studies are needed to evaluate its biological effects.

Purpose Hyperbaric oxygen treatment (HBOT) has been found to improve the healing of poorly oxygenated tissues. This study aimed to investigate the influence of HBOT on the healing in ischemic colorectal anastomosis. Methods Forty Wistar rats were randomly divided into a treatment group that received HBOT for 10 consecutive days (7 days before and 3 days after surgery), or in a control group, which did not receive the therapy. Colectomy with an ischemic anastomosis was performed in all rats. In each group, the rats were followed for 3 or 7 days after surgery to determine the influence of HBOT on anastomotic healing. Results Five rats from each group died during follow-up. No anastomotic dehiscence was seen in the HBOT group, compared to 37.5 % and 28.6 % dehiscence in the control group on postoperative day (POD) 3 and 7, respectively. The HBOT group had a significantly higher bursting pressure (130.9 ± 17.0 mmHg) than the control group (88.4 ± 46.7 mmHg; p = 0.03) on POD 3. On POD 3 and POD 7, the adhesion severity was significantly higher in the control groups than in the HBOT groups (p

Background Treatment of perforated diverticulitis depends on disease severity classified according to Hinchey’s preoperative classification. This study assessed the accuracy of preoperative staging of perforated diverticulitis by computerized tomography (CT) scanning. Methods All patients who presented with perforated diverticulitis between 1999 and 2009 in two teaching hospitals of Rotterdam, the Netherlands, and in addition had a preoperative CT scan within 24 h before emergency surgery were included. Two radiologists reviewed all CT scans and were asked to classify the severity of the disease according to the Hinchey classification. The CT classification was compared to Hinchey’s classification at surgery. Results Seventy-five patients were included, 48 of whom (64 %) were classified Hinchey 3 or 4 perforated diverticulitis during surgery. The positive predictive value of preoperative CT scanning for different stages of perforated diverticulitis ranged from 45 to 89 %, and accuracy was between 71 and 92 %. The combination of a large amount of free intra-abdominal air and fluid was strongly associated with Hinchey 3 or 4 and therefore represented a reliable indicator for required surgical treatment. Conclusions The accuracy of predicting Hinchey’s classification by preoperative CT scanning is not very high. Nonetheless, free intra-abdominal air in combination with diffuse fluid is a reliable indication for surgery as it is strongly associated with perforated diverticulitis with generalized peritonitis. In 42 % of cases, Hinchey 3 perforated diverticulitis is falsely classified as Hinchey 1 or 2 by CT scanning.

Objective: The objective of the study was to determine the long-term effect of the use of a hyaluronic acid-carboxymethylcellulose membrane (Seprafilm) on the incidence of adhesions and subsequent small-bowel obstruction and chronic abdominal complaints after colorectal surgery (Hartmann's procedure). Background: Adhesions occur frequently after abdominal surgery and are the most common cause of bowel obstruction, chronic abdominal pain, and infertility. The risk for adhesion-related readmission in the first 10 years after colorectal surgery is as high as 30%. To reduce the formation of adhesions, a mechanical barrier composed of hyaluronic acid and carboxymethylcellulose was developed, to prevent adherence of tissues after abdominal surgery. Longterm results concerning the incidence of small-bowel obstruction and chronic abdominal pain are lacking. Methods: Between April 1996 and September 1998, 71 patients requiring Hartmann's procedure for sigmoid diverticulitis or obstructed rectosigmoid were randomized to either intraperitoneal placement of Seprafilm under the midline and in the pelvis or as a control. Direct visual evaluation of the incidence and severity of adhesions was performed laparoscopically in 42 patients at second-stage surgery for restoration of the continuity of the colon. The results of this study were published in 2002. In 2006, the patients' general practitioners were interviewed by means of a questionnaire concerning their patients' health. The patients who were still alive were interviewed and asked to fill out 2 questionnaires concerning pain and quality of life (VAS-pain score, EQ-5D, and SF-36). In 2009, the medical records of the patients were evaluated for adhesion-related hospital re-admissions. Results: Of the 42 evaluated patients, 35 (16 in the Seprafilm group, 19 in the control group) could be enrolled in the long-term follow-up. Median follow-up was 126 months (range 41-148) for the Seprafilm group and 128 months (range 49-149) months for the control group. Incidence of chronic (3 months or longer existing) abdominal complaints was significantly lower in the Seprafilm group compared with controls (35.3% vs. 77.8%, respectively; P = 0.018). Incidence of small-bowel obstruction showed no significant difference in favor of the Seprafilm group; no small-bowel obstructions occurred in the Seprafilm group, whereas in the control group 2 cases of small-bowel obstruction were found to have occurred. Evaluation of the quality of life questionnaires did not reveal significant differences between the 2 groups. Conclusions: In Hartmann's procedure, Seprafilm placement does not provide protection against small-bowel obstruction. Incidence of chronic abdominal complaints is significantly lower after use of Seprafilm.

Background Inguinal nerve identification during open inguinal hernia repair is associated with less chronic postoperative pain. However, most Dutch surgeons do not identify all three inguinal nerves when carrying out this procedure. The aim of this study was to evaluate the feasibility of a nerve-recognizing Lichtenstein hernia repair and to measure the extra time required for surgery Methods Forty patients with primary inguinal hernia were operated on following the nerve-recognizing Lichtenstein hernia repair by four experienced hernia surgeons from four different Dutch teaching hospitals. The additional time needed to identify each individual nerve was recorded, and iatrogenic nerve injuries and anatomical characteristics were registered. Results Identification of the iliohypogastric and ilioinguinal nerves was each performed within 1 min. Identification of the genital branch of the genitofemoral nerve was notably more difficult but could usually be performed within 2 min. Identification of the cremasteric vein, running parallel to the genital branch, was less comprehensive. The incidence of major anatomical variations was low. Twenty-five per cent of ilioinguinal nerves, however, could not be identified. In five patients inguinal nerves were damaged iatrogenically during standard manoeuvres of the Lichtenstein hernia repair. Conclusion Three-nerve-recognizing Lichtenstein hernia repair is feasible and non-time consuming if the surgeon has appropriate anatomical knowledge. In view of the low incidence of major anatomical variations, knowledge of standard inguinal nervous anatomy should be adequate. This procedure could enable the surgeon to prevent or recognize iatrogenic nerve damage and offer an opportunity to perform deliberate neurectomy as an alternative to accidental nerve injury.

Background Preparative myeloablative conditioning regimens for allogeneic hematopoietic stem-cell transplantation (HSCT) may control malignancy and facilitate engraftment but also contribute to transplant related mortality, cytokine release, and acute graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have decreased transplant related mortality but the incidence of acute GVHD, while delayed, remains unchanged. There are currently no in vivo allogeneic models of RIC HSCT, limiting studies into the mechanism behind RIC-associated GVHD. Methods We developed two RIC HSCT models that result in delayed onset GVHD (major histocompatibility complex mismatched (UBI-GFP/BL6 [H-2b]→BALB/c [H-2d]) and major histocompatibility complex matched, minor histocompatibility mismatched (UBI-GFP/BL6 [H-2b]→BALB.B [H-2b])) enabling the effect of RIC on chimerism, dendritic cell (DC) chimerism, and GVHD to be investigated. Results In contrast with myeloablative conditioning, we observed that RIC-associated delayed-onset GVHD is characterized by low production of tumor necrosis factor-α, maintenance of host DC, phenotypic DC activation, increased T-regulatory cell numbers, and a delayed emergence of activated donor DC. Furthermore, changes to the peritransplant milieu in the recipient after RIC lead to the altered activation of DC and the induction of T-regulatory responses. Reduced intensity conditioning recipients suffer less early damage to GVHD target organs. However, as donor cells engraft, activated donor DC and rising levels of tumor necrosis factor-α are associated with a later onset of severe GVHD. Conclusions Delineating the mechanisms underlying delayed onset GVHD in RIC HSCT recipients is vital to improve the prediction of disease onset and allow more targeted interventions for acute GVHD.

Morbidity associated with open inguinal hernia repair (IH repair) mainly consists of chronic pain. The aim of this study was to identify possible disparities between state-of-the-art Lichtenstein repair, and its application in general practice.A questionnaire was mailed to all surgeons and surgical residents (n = 1,374) in the Netherlands in February 2005. The objective was to determine the state of general practice with respect to technical steps during the Lichtenstein repair that are suggested to be involved in the development of chronic pain, as recently updated by Lichtenstein's successor, Amid.More than half of the respondents do not act according to the Lichtenstein guidelines with respect to surgical steps that are suggested to be involved with the origin of chronic pain of somatic origin. Compliance with Amid's guidelines with respect to the handling of the nerves is variable. Surgeons conducting high numbers of IH repair are more likely to operate according to the key principles of the state-of-the-art Lichtenstein repair.There is a substantial disparity between the state-of-the-art Lichtenstein repair and its application in general practice with respect to steps that are suggested to play a role in the origin of chronic groin pain.

Background Inguinal hernias are a common entity with nearly 31,000 repairs annually in The Netherlands and over 800,000 in the USA. The aim of the present study is to determine whether a laparoscopically diagnosed patent processus vaginalis (PPV) is a risk factor for the development of groin hernia. Methods The study population was originally composed of 599 consecutive cases (189 male, 32%) of laparoscopic transperitoneal surgery for different indications performed in 4 teaching hospitals in The Netherlands between November 1998 and February 2002. During laparoscopy, the deep inguinal ring was inspected bilaterally. The PPV group was compared with the obliterative processus vaginalis (OPV) group. Results After a mean follow-up of 5.5 years, the studied population consisted of 337 cases (94 male, 28%). In this study 12% of the studied population appeared to have PPV in adult life. The percentage PPV of our study group is much higher than the percentage of hernia repairs performed in the Dutch population. A greater proportion (12%) of hernia repairs in the PPV group was found as compared with the OPV group (3%). The chance of developing an inguinal hernia within 5.3 years is four times higher in the group with PPV. No significant correlation between age and the prevalence of PPV was observed. Conclusion This study demonstrates that PPV is an etiologic factor and a risk factor for acquiring an indirect inguinal hernia in adults.

Background Peroperative identification and subsequent division or preservation of the inguinal nerves during open hernia repair may influence the incidence of chronic postoperative pain. Methods A systematic literature review was performed to identify studies investigating the influence of different types of nerve management. Results Based on three randomized studies the pooled mean percentage of patients with chronic pain after identification and division of the ilioinguinal nerve was similar to that after identification and preservation of the ilioinguinal nerve. Two cohort studies suggested that the incidence of chronic pain was significantly lower after identification of all inguinal nerves compared with no identification of any nerve. Another cohort study reported a significant difference in the incidence of chronic pain in favour of identification and facultative pragmatic division of the genital branch of the genitofemoral nerve compared with no identification at all. Conclusion The nerves should probably be identified during open hernia repair. Division of and preservation of the ilioinguinal nerve show similar results.

Prosthetic incisional hernia repair (PIHR) is superior to primary closure in preventing hernia recurrence. Serious complications have been associated with the use of prosthetic material. Complications of subsequent surgical interventions after prior PIHR in relation to its anatomical position were the objectives of this study. Patients who underwent subsequent laparotomy/laparoscopy after PIHR between January 1992 and February 2005 at our institution were evaluated. Intraperitoneal and preperitoneal mesh was related to complication rates after subsequent surgical interventions. Sixty-six of 335 patients underwent re-laparotomy after PIHR. The perioperative course was complicated in 76% (30/39) of procedures with intraperitoneal placed grafts compared to 29% (8/27) of interventions with preperitoneally positioned meshes (P < 0.001). Small bowel resections were necessary in 21% of the intraperitoneal group (8/39) versus 0% in the preperitoneal group. Surgical site infection rates were higher in the intraperitoneal group (10/39, 26%, versus 1/27, 4%). Enterocutaneous fistula formation was rare and occurred in two patients after subsequent laparotomy (5%). Re-laparotomy after PIHR with polypropylene meshes are associated with more preoperative and postoperative complications when the mesh is placed intraperitoneally. Therefore 0intraperitoneal positioning of polypropylene mesh at incisional hernia repair should be avoided if possible.

Background: Hartmann's gallbladder pouch was the subject of an article in The Lancet 60 years ago. It has regained new interest in view of laparoscopic cholecystectomy. However, different opinions exist with regard to its incidence and nature. To elucidate these discrepancies, a descriptive study was performed with regard to the incidence and morphology of Hartmann's pouch. Methods: Gallbladders were obtained after elective laparoscopic cholecystectomy. In addition, gallbladders were obtained during routine postmortem examination. The gallbladders were divided in two groups: those with Hartmann's pouch and those without Hartmann's pouch. All the gallbladders were examined macroscopically and microscopically. Fisher's Exact Probability Test (p < 0.05, two-tailed) was used to analyze the data. Results: A total of 98 gallbladders were examined: 49 obtained after laparoscopic or open cholecystectomy and 49 obtained after postmortem examination. Among the gallbladders with Hartmann's pouch (n = 51), 65% contained stones and 35% had no stones. Among the gallbladders without Hartmann's pouch, 43% contained stones and 57% had no stones. Macroscopically, in all the gallbladders with Hartmann's pouch, the pouch was observed to result from adhesions between the cystic duct and the neck of the gallbladder. After cleavage of these adhesions, the phenomenon of Hartmann's pouch was abolished in all cases. Conclusions: Hartmann's gallbladder pouch is a frequent but inconstant feature of normal and pathologic human gallbladders. There is a significant association between the presence of Hartmann's pouch and stones (p < 0.05). Adhesions between the cystic duct and the neck of the gallbladder are responsible for Hartmann's pouch. Consequently, Hartmann's gallbladder pouch is a morphologic rather than an anatomic entity.

The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p