A case of pancreatic cancer with concomitant median arcuate ligament syndrome treated successfully using an allograft arterial transposition

An association of pancreatic cancer and median arcuate ligament syndrome (MALS) is a rare and challenging situation in terms of treatment. A 60-year-old man diagnosed with pancreatic cancer underwent laparotomy. A pancreaticoduodenectomy was planned, but during the resection part of the operation, a celiac artery stenosis was noticed. The patient was diagnosed with MALS causing almost total celiac artery occlusion, with no radiological solution. The patient was re-operated the next day, and an iliac artery allograft was used for aorta-proper hepatic artery reconstruction, concomitant with the total pancreaticoduodenectomy. Preoperative meticulous evaluation of vascular structures of the celiac trunk and its branches is important, especially in pancreatic surgery. A vascular allograft may be a lifesaving alternative when vascular reconstruction is necessary

Clinical Application of the Hanover Classification for Iatrogenic Bile Duct Lesions

Background. There is only limited evidence available to justify generalized clinical classification and treatment recommendations for iatrogenic bile duct lesions. Methods. Data of 93 patients with iatrogenic bile duct lesions was evaluated retrospectively to analyse the variety of encountered lesions with the Hanover classification and its impact on surgical treatment and outcomes. Results. Bile duct lesions combined with vascular lesions were observed in 20 patients (21.5%). 18 of these patients were treated with additional partial hepatectomy while the majority were treated by hepaticojejunostomy alone (n = 54). Concomitant injury to the right hepatic artery resulted in additional right anatomical hemihepatectomy in 10 of 18 cases. 8 of 12 cases with type A lesions were treated with drainage alone or direct suture of the bile leak while 2 patients with a C2 lesion required a Whipple's procedure. Observed congruence between originally proposed lesion-type-specific treatment and actually performed treatment was 66–100% dependent on the category of lesion type. Hospital mortality was 3.2% (n = 3). Conclusions. The Hannover classification may be helpful to standardize the systematic description of iatrogenic bile duct lesions in order to establish evidence-based and lesion-type-specific treatment recommendations

Adult Kasabach-Merritt Syndrome due to Hepatic Giant Hemangioma

Cavernous hemangiomas are the most common benign tumors of the liver. They can reach enormous sizes and cause various complications. Kasabach-Merritt syndrome is a rare but serious complication characterized by consumptive coagulopathy caused by the hemangioma; mortality rate ranges between 10 and 37%. More than 80% of cases occur within the first year of life. Goals of the treatment are to control the coagulopathyand thrombocytopenia as well as to eradicate the hemangioma. Different nonsurgical treatment regimens are performed, includingsystemic corticosteroids, irradiation and various chemicals. Surgery should be limited to symptomatic or complicated cases. Although difficult, resection of the tumor is usually curative. Here we present a 44-year-old woman with giant hepatic hemangioma causing Kasabach-Merritt syndrome managed by enucleation

Liver Transplantation for Hepatocellular Carcinoma: A Single Center Resume Overlooking Four Decades of Experience

Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included. Predictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and χ2-tests where appropriate. Results. HCCR was the single strongest hazard for survival (exp⁡B=10.156). Hazards for HCCR were tumor staging beyond the histologic MILAN (exp⁡B=3.645), bilateral tumor spreading (exp⁡B=14.505), tumor grading beyond G2 (exp⁡B=8.668), and vascular infiltration of small or large vessels (exp⁡B=11.612, exp⁡B=18.324, resp.). Grading beyond G2 (exp⁡B=10.498) as well as small and large vascular infiltrations (exp⁡B=13.337, exp⁡B=16.737, resp.) was associated with higher hazard ratios for long-term survival as compared to liver transplantation beyond histological MILAN (exp⁡B=4.533). Tumor dedifferentiation significantly correlated with vascular infiltration (χ2p=0.006) and intrahepatic tumor spreading (χ2p=0.016). Conclusion. LT enables survival from HCC. HCC dedifferentiation is associated with vascular infiltration and intrahepatic tumor spreading and is a strong hazard for HCCR and survival. Pretransplant tumor staging should include grading by biopsy, because grading is a reliable and easily accessible predictor of HCCR and survival. Detection of dedifferentiation should speed up the allocation process

A Depleting Anti-CD45 Monoclonal Antibody as Isolated Conditioning for Bone Marrow Transplantation in the Rat

Objective A monoclonal antibody (mAb) against the leukocyte common antigen CD45 (RT7 in rats) could facilitate bone marrow transplantation (BMT). This study in rats evaluates a depletive rat anti-RT7(a) mAb as isolated tool for BMT conditioning without using irradiation or any chemotherapeutic /immunosuppressive agent. Methods The model used a CD45 di-allelic polymorphism (RT7(a)/RT7(b)). The anti-RT7(a) mAb was intravenously administered to LEW. 1W rats (RT1(u)RT7(a)) at 5, 10 and 15 mg/kg. 1x10(8) BM cells of MHC syngeneic (RT1(u)), MHC disparate (RT1(l)) or MHC haploidentical (RT1(u/l)) donors were transplanted. All BM donor strains carried the RT7(b) allele so that their CD45(+) cells were not affected by the anti-RT7(a) mAb. Recipients were monitored for reconstitution and donor-chimerism in blood leukocytes. Results mAb dosages of 5 or 10mg/kg were myelosuppressive, whereas 15mg/kg was myeloablative. Multi-lineage donor-chimerism at day 100 indicated engraftment ofMHC syngeneic BM after any used mAb dosage (5 mg/kg: 46+/-7%; 10mg/kg: 62+/-5%; 15mg/kg: 80+/-4%). MHC disparate BM resulted in autologous reconstitution after conditioning by 10mg/kg of the mAb and caused transient chimerism ending up in death associated with aplasia after conditioning by 15mg/kg of the mAb. MHC haploidentical BM (F1 to parental) engrafted only after conditioning by 15 mg/kg (chimerism at day 100: 78+/-7%). Abandonment of alpha/beta TCR+ cell depletion fromBMgrafts impaired the engraftment process after conditioning using 15 mg/kg of the mAb in theMHC syngeneic setting (2 of 6 recipients failed to engraft) and the MHC haploidentical setting (3 of 6 recipients failed). Conclusion This depletive anti-RT7(a) mAb ismyelosuppressive and conditions for engraftment of MHC syngeneic BM. The mAb also facilitates engraftment ofMHC haploidentical BM, if amyeloablative dose is used. RT7(b) expressing, BM- seeded alpha/beta TCR+ cells seem to impair the engraftment process after myeloablative mAb conditioning

Preoperative leukocytosis and the resection severity index are independent risk factors for survival in patients with intrahepatic cholangiocarcinoma

Purpose!#!The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. Despite advances in surgical and non-surgical treatment, reported outcomes are still poor and surgical resection remains to be the only chance for long-term survival of affected patients. The identification and validation of prognostic factors and scores, such as the recently introduced resection severity index, for postoperative morbidity and mortality are essential to facilitate optimal therapeutic regimens.!##!Methods!#!This is a retrospective analysis of 269 patients undergoing resection of histologically confirmed intrahepatic cholangiocarcinoma between February 1996 and September 2018 at a tertiary referral center for hepatobiliary surgery. Regression analyses were performed to evaluate potential prognostic factors, including the resection severity index.!##!Results!#!Median postoperative follow-up time was 22.93 (0.10-234.39) months. Severe postoperative complications (≥ Clavien-Dindo grade III) were observed in 94 (34.9%) patients. The body mass index (p = 0.035), the resection severity index (ASAT in U/l divided by Quick in % multiplied by the extent of liver resection graded in points; p = 0.006), additional hilar bile duct resection (p = 0.005), and number of packed red blood cells transfused during operation (p = 0.036) were independent risk factors for the onset of severe postoperative complications. Median Kaplan-Meier survival after resection was 27.63 months. Preoperative leukocytosis (p = 0.003), the resection severity index (p = 0.005), multivisceral resection (p = 0.001), and T stage ≥ 3 (p = 0.013) were identified as independent risk factors for survival.!##!Conclusion!#!Preoperative leukocytosis and the resection severity index are useful variables for preoperative risk stratification since they were identified as significant predictors for postoperative morbidity and mortality, respectively

A multicentre, randomized clinical trial comparing the Veriset haemostatic patch with fibrin sealant for the management of bleeding during hepatic surgery

Background: Bleeding during hepatic surgery is associated with prolonged hospitalization and increased morbidity and mortality. The Veriset haemostatic patch is a topical haemostat comprised of an absorbable backing made of oxidized cellulose and self-adhesive hydrogel components. It is designed to achieve haemostasis quickly and adhere to tissues without fixation. Methods: A prospective, randomized, multicentre, single-blinded study (n = 50) was performed to compare the use of a Veriset haemostatic patch with a fibrin sealant patch (TachoSil (R)) (control) in the management of diffuse bleeding after hepatic surgery. Patients were randomized following the confirmation of diffuse bleeding requiring the use of a topical haemostat. Time to haemostasis was assessed at preset intervals until haemostasis was achieved. Results: Both groups were similar in comorbidities and procedural techniques. The median time to haemostasis in the group using the Veriset haemostatic patch was 1.0min compared with 3.0min in the control group (P < 0.001; 3-min minimum application time for the control patch). This result was independent of bleeding severity and surface area. Both products had similar safety profiles and no statistical differences were observed in the occurrence of adverse or device-related events. Conclusions: Regardless of bleeding severity or surface area, the Veriset haemostatic patch achieved haemostasis in this setting significantly faster than the control device in patients undergoing hepatic resection. It was safe and easy to handle in open hepatic surgery

Weight indices of recipients receiving BM with or without depletion of donor-derived α/β TCR⁺ cells.

<p><i>LEW</i>.<i>1W (RT1</i>^<i>u</i>, <i>RT7</i>^<i>a</i><i>) recipients were conditioned by 15 mg/kg of anti-RT7</i>^<i>a</i><i>mAb 3 days prior to transplantation of 1 x 10</i>^<i>8</i><i>BMC from MHC syngeneic (LEW</i>.<i>1U-7B</i>: <i>RT1</i>^<i>u</i>, <i>RT7</i>^<i>b</i><i>)</i>, <i>MHC haploidentical (LEW</i>.<i>1U-7B x LEW</i>.<i>7B</i>: <i>RT1</i>^<i>u/l</i>, <i>RT7</i>^<i>b</i><i>) or MHC disparate (LEW</i>.<i>7B</i>: <i>RT1</i>^<i>l</i>, <i>RT7</i>^<i>a</i><i>) donors</i>. <i>BM grafts were depleted from α/β TCR</i>^<i>+</i><i>cells in vitro (TCD) or were kept untreated (no TCD)</i>. <i>Thus</i>, <i>1 x 10</i>^<i>8</i><i>BMC contained 5</i>.<i>4 x 10</i>^<i>6</i><i>α/β TCR</i>^<i>+</i><i>cells (MHC syngeneic)</i>, <i>5</i>.<i>1 x 10</i>^<i>6</i><i>α/β TCR</i>^<i>+</i><i>(MHC haploidentical) and 4</i>.<i>2 x 10</i>^<i>6</i><i>α/β TCR</i>^<i>+</i><i>cells (MHC disparate)</i>, <i>respectively</i>, <i>when untreated</i>. <i>Weight indices were calculated by dividing the actual weight of the recipients through the baseline weight at the time point of BMT conditioning (= anti-RT7</i>^<i>a</i><i>mAb injection)</i>. <i>Weight indices were calculated and depicted as mean values +/- standard deviation per group (</i>^<i>…</i><i>○</i>^<i>…</i><i>depletion of</i> α/β TCR⁺ cells; –<i>■– no depletion of</i> α/β TCR⁺ cells) <i>Statistical analyses were performed applying the unpaired t test (* p < 0</i>.<i>05)</i>.</p

Multi-lineage chimerism in stable recipients of MHC haploidentical BM grafts conditioned by 15 mg/kg of anti-RT7^a mAb at day 200.

<p><i>Blood samples of long-term surviving recipients of MHC haploidentical BMT (F1 (LEW.7B x LEW.1U-7B: RT1^l/u RT7^b) → LEW.1W: RT1^u, RT7^a) were analysed by flow cytometry for donor-derived chimerism (RT7^b) within leukocyte lineages at day 200. Used mAbs were anti-α/β TCR mAb (R73) for T-lymphocytes, anti-CD45RA (OX33) for B-lymphocytes, anti-granulocytes (HIS48) for granulocytes and anti-RT7^b (HIS41) for donor-derived cells.</i></p