Positioning strictureplasty in the treatment of extensive Crohn's disease ileitis: a comparative study with ileocecal resection.

PURPOSE: The optimal surgical approach to extensive Crohn's disease (CD) terminal ileitis is debated. To date, no studies have directly compared the short- and long-term outcomes of modified side-to-side isoperistaltic strictureplasty over the valve (mSSIS) to traditional ileocecal resection. METHODS: A retrospective, observational, comparative study was conducted in consecutive CD patients operated for extensive involvement of the terminal ileum (≥ 20 cm). Ninety-day postoperative morbidity was assessed using the comprehensive complication index (CCI). Surgical recurrence was defined as the need for any surgical intervention related to CD during the follow-up period. Endoscopic remission was defined as ≤ i2a, according to the modified Rutgeerts score. Deep remission was defined as the combination of endoscopic remission and absence of clinical symptoms. Perioperative factors related to clinical recurrence were evaluated. RESULTS: Eighty-seven patients were included (47 (54%) ileocecal resection and 40 (46%) mSSIS). Median follow-up was 56 (IQR 34.7-94.4) and 72 (IQR 48.3-87.2) months for resection and mSSIS, respectively (p < 0.001). No mortality occurred. Mean CCI was 9.1 vs 8.5 for ileocecal resection and mSSIS, respectively (p = 0.48). Throughout the follow-up, 8 patients in the resection group (17%) and 5 patients in the mSSIS group (12.5%) experienced surgical recurrence (p = 0.393). Thirty-seven (92.5%) of patients kept the mSSIS. No difference in deep remission was observed (41% vs 22.5%, p = 0.34). CONCLUSIONS: Modified SSIS seems to be non-inferior in terms of safety, recurrence, and durability to traditional resections with the advantage of mitigating the risk of a short bowel syndrome. Larger prospective studies are required to confirm these findings.

A new intraductal radiofrequency ablation device for inoperable biliopancreatic tumors complicated by obstructive jaundice: the IGNITE-1 study.

Background and study aims Biliary stenting of unresectable malignant bile duct obstruction is generally accepted as the standard of care but it can be hampered by tumor ingrowth and stent dysfunction. We aimed to test the feasibility, safety, and biliary patency rate of a new endoscopically applied intraductal radiofrequency ablation (RFA) device. Patients and methods Eighteen patients with inoperable malignant biliary obstruction underwent endoscopic retrograde cholangiopancreatography (ERCP)-directed RFA and stenting. Results Between December 2014 and November 2015, 18 patients underwent RFA to the intended region, with no complications within 3 months of the procedure. Bilirubin levels post-RFA and stenting decreased significantly (7.8 ±â€Š1 mg/dL to 1.7 ±â€Š0.4 mg/dL; P < 0.001). At 90 and 180 days post-intervention, biliary patency was maintained in 80 % and 69 % of patients still alive at that time, respectively. The median overall stent patency was 110 days (range 16 - 374), with a median patient survival of 227 days (range 16 - 374). Conclusion Intraductal RFA using a new device in patients with inoperable biliopancreatic cancer complicated by jaundice appeared feasible and safe with acceptable biliary patency. Randomized trials with prolonged follow-up are warranted.ClinTrials.gov: NCT02468076.

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival.

BACKGROUND: The purpose of this study was to retrospectively assess the technical and clinical outcomes, overall survival and prognostic factors for prolonged survival after yttrium-90 ((90)Y) radioembolization as a salvage therapy for patients with chemorefractory liver-only or liver-dominant colorectal metastases. MATERIAL AND METHODS: From January 2005 to January 2014, all the patients selected for (90)Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed. RESULTS: In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed (90)Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n = 39; 55%), abdominal discomfort (n = 33; 47%), nausea (n = 5; 7%), fever (n = 14; 20%), diarrhea (n = 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n = 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels. CONCLUSION: (90)Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.

Impact of early parenteral nutrition on muscle and adipose tissue compartments during critical illness.

OBJECTIVE: The goal of enhanced nutrition in critically ill patients is to improve outcome by reducing lean tissue wasting. However, such effect has not been proven. This study aimed to assess the effect of early administration of parenteral nutrition on muscle volume and composition by repeated quantitative CT. DESIGN: A preplanned substudy of a randomized controlled trial (Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients [EPaNIC]), which compared early initiation of parenteral nutrition when enteral nutrition was insufficient (early parenteral nutrition) with tolerating a pronounced nutritional deficit for 1 week in ICU (late parenteral nutrition). Late parenteral nutrition prevented infections and accelerated recovery. SETTING: University hospital. PATIENTS: Fifteen EPaNIC study neurosurgical patients requiring prescheduled repeated follow-up CT scans and six healthy volunteers matched for age, gender, and body mass index. INTERVENTION: Repeated abdominal and femoral quantitative CT images were obtained in a standardized manner on median ICU day 2 (interquartile range, 2-3) and day 9 (interquartile range, 8-10). Intramuscular, subcutaneous, and visceral fat compartments were delineated manually. Muscle and adipose tissue volume and composition were quantified using standard Hounsfield Unit ranges. MEASUREMENTS AND MAIN RESULTS: Critical illness evoked substantial loss of femoral muscle volume in 1 week's time, irrespective of the nutritional regimen. Early parenteral nutrition reduced the quality of the muscle tissue, as reflected by the attenuation, revealing increased intramuscular water/lipid content. Early parenteral nutrition also increased the volume of adipose tissue islets within the femoral muscle compartment. These changes in skeletal muscle quality correlated with caloric intake. In the abdominal muscle compartments, changes were similar, albeit smaller. Femoral and abdominal subcutaneous adipose tissue compartments were unaffected by disease and nutritional strategy. CONCLUSIONS: Early parenteral nutrition did not prevent the pronounced wasting of skeletal muscle observed over the first week of critical illness. Furthermore, early parenteral nutrition increased the amount of adipose tissue within the muscle compartments.

Upper esophageal sphincter impedance as a marker of sphincter opening diameter.

The measurement of the physical extent of opening of the upper esophageal sphincter (UES) during bolus swallowing has to date relied on videofluoroscopy. Theoretically luminal impedance measured during bolus flow should be influenced by luminal diameter. In this study, we measured the UES nadir impedance (lowest value of impedance) during bolus swallowing and assessed it as a potential correlate of UES diameter that can be determined nonradiologically. In 40 patients with dysphagia, bolus swallowing of liquids, semisolids, and solids was recorded with manometry, impedance, and videofluoroscopy. During swallows, the UES opening diameter (in the lateral fluoroscopic view) was measured and compared with automated impedance manometry (AIM)-derived swallow function variables and UES nadir impedance as well as high-resolution manometry-derived UES relaxation pressure variables. Of all measured variables, UES nadir impedance was the most strongly correlated with UES opening diameter. Narrower diameter correlated with higher impedance (r = -0.478, P < 0.001). Patients with <10 mm, 10-14 mm (normal), and ≥ 15 mm UES diameter had average UES nadir impedances of 498 ± 39 Ohms, 369 ± 31 Ohms, and 293 ± 17 Ohms, respectively (ANOVA P = 0.005). A higher swallow risk index, indicative of poor pharyngeal swallow function, was associated with narrower UES diameter and higher UES nadir impedance during swallowing. In contrast, UES relaxation pressure variables were not significantly altered in relation to UES diameter. We concluded that the UES nadir impedance correlates with opening diameter of the UES during bolus flow. This variable, when combined with other pharyngeal AIM analysis variables, may allow characterization of the pathophysiology of swallowing dysfunction.

Conservative management of esophageal perforations during pneumatic dilation for idiopathic esophageal achalasia.

BACKGROUND & AIMS: Esophageal perforation is the most serious adverse event of pneumatic dilation (PD) for achalasia; it is usually managed by surgical repair. We investigated risk factors for esophageal perforation after PD and evaluated safety and long-term outcome of nonsurgical management strategies. METHODS: We analyzed medical records of patients with achalasia who were treated with PD from 1992-2010 at the University Hospital Gasthuisberg in Leuven, Belgium; all patients with esophageal perforation were contacted to determine long-term outcomes. Achalasia outcomes were assessed by using the Vantrappen criteria. RESULTS: Of 830 PD procedures performed on 372 patients with manometry-confirmed achalasia (57 ± 1 years, 51% male), 16 were complicated by transmural esophageal perforation (4.3% of patients, 1.9% of dilations). Age >65 years was the only significant risk factor for complications (odds ratio, 3.5; 95% confidence interval, 1.2-10.2). All patients were treated conservatively with broad-spectrum antibiotics and nothing by mouth. In 6 patients (38%) the clinical course was further complicated by a pleural effusion, which required a drain in 4 patients. One patient (6%) died of mediastinal hemorrhage within 12 hours after PD. Patients with complications were discharged after 19 ± 2.3 days, compared with 4 ± 0.2 days for those without complications (P < .0001). Long-term outcomes (mean follow-up, 84 ± 14 months) were determined for 12 patients (75%); 11 had excellent or good outcomes (69%), and 1 had a moderate outcome (6%). CONCLUSIONS: Age >65 years is a significant risk factor for esophageal perforation after PD. Nonsurgical management of transmural esophageal tears is feasible, with favorable short-term and long-term outcomes, but is not devoid of complications.

Long-term monitoring of infliximab therapy for perianal fistulizing Crohn's disease by using magnetic resonance imaging.

BACKGROUND & AIMS: Magnetic resonance imaging (MRI) is used to assess the outcome of infliximab (IFX) therapy in patients with perianal fistulizing Crohn's disease (pfCD). However, few long-term data are available about its efficacy. METHODS: We assessed 59 patients with pfCD by MRI and clinical evaluation at baseline. Treated patients then received paired clinical and MRI examinations for a median time period of 36 (11-53.3) weeks. Short-, mid-, and long-term effects of therapy, as well as the ability of MRI to predict treatment outcome and need for surgery, were evaluated. RESULTS: Compared with the baseline MRI, the short-term follow-up MRI (n = 29) revealed a reduced number of fistula tracks in 13.8% and in the inflammatory activity in 55.2% of patients, respectively; mid-term MRI (n = 25) in 56% and in 52%, respectively; and long-term MRI (n = 13) in 15.4% and in 31%, respectively. Improvement of pfCD based on MRI results coincided with clinical improvement in 54.7% of the patients. Short-term and mid-term (but not long-term) MRI showed a significant decrease in the activity score. Therapy outcome was worse among patients with persisting fistulas (P = .01), collections (P = .009), and rectal wall involvement (P = .01) in the final MRI. Patients with single-branched fistulas (P < .0001) and collections (P = .006) in their baseline MRI were more likely to undergo surgery. CONCLUSIONS: MRI is a useful technique for evaluation of pfCD during the first year of follow-up. In the long-term, the MRI improvement coincides with clinical and endoscopic response to IFX in 50% of the patients.

The inferior mesoiliacal shunt: A novel shunt for refractory rectal variceal bleeding due to splanchnic thrombosis.

Surgical shunt therapy may be required when pharmacologic, endoscopic, and radiologic treatment of chronic splanchnic vein thrombosis have failed. In this case report, we present a new interposition shunt for the treatment of refractory rectal variceal bleeding: the inferior mesoiliacal shunt between the inferior mesenteric vein and the left common iliac vein using a cryopreserved iliac venous graft. The postoperative course was complicated by shunt thrombosis at day 2, probably owing to inadvertent interruption of anticoagulation and a decrease in the shunt flow rate. Surgical thrombectomy was performed successfully. The patient presented no relapse of rectal bleeding and was asymptomatic and well at the 12-month follow-up.

Risk Stratification for Surgery in Stricturing Ileal Crohn's Disease: The BACARDI Risk Model.

BACKGROUND AND AIM: Transmural inflammation in Crohn's disease [CD] leads to stricturing or penetrating complications. Factors impacting on the need and timing of surgery in ileal stricturing CD [IS-CD] are understudied. Our aim was to identify risk factors in IS-CD associated with the need for surgery over time. METHODS: All cross-sectional imaging [XSI] performed for CD between 2006 and 2015 in a tertiary referral centre was analysed. The electronic charts of patients with IS-CD were reviewed for demographic, clinical, biochemical, imaging, genetic, and endoscopic factors. An independent cohort was used for validation. RESULTS: A total of 1803 XSI were performed in 957 patients with CD. IS-CD was diagnosed in 235 patients, and 161 of these [69%] needed surgery. Prestenotic dilation (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.22-3.45, p = 0.007], C-reactive protein at diagnosis of IS-CD > 11 mg/L [HR 1.53, 95% CI 1.05-2.24, p = 0.026], Montreal B3 phenotype [HR 1.58, 95% CI 1.06-2.36, p = 0.023], previous/current anti-tumour necrosis factor [TNF] exposure [HR 1.44, 95% CI 1.00-2.06, p = 0.048], and presence of at least one NOD2 rs2066844 risk allele [HR 1.51, 95% CI 1.02-2.23, p = 0.038] significantly impacted on the need for surgery in multivariate analysis. The risk stratification model [BACARDI] yielded a surgery-free survival after 5 years of 77%, 38%,19%, and 0% for the low, medium, high, and all risk groups, respectively. Based on an independent cohort of 27 patients, the results were validated and demonstrated adequate performance. CONCLUSIONS: This risk model can facilitate therapeutic decisions in IS-CD and suggest the correct time for surgery in daily clinical practice.

The operative risk and natural history after the diagnosis of ileal penetrating Crohn's disease.

BACKGROUND AND PURPOSE: Crohn's disease (CD) is marked by transmural inflammation of the bowel wall leading to stricturing and/or penetrating complications in the majority of patients. The natural history and operative risk after the diagnosis of an ileal penetrating complication is understudied. The aim was to study the disease course and need for surgery in patients diagnosed with a penetrating ileal CD complication and to assess the risk factors associated with worse postoperative outcome. PATIENTS AND METHODS: In this cohort study, all cross-sectional imaging exams (computed tomography and/or magnetic resonance imaging) performed between 2006 and 2014 in patients with CD in a tertiary referral centre were reviewed for the presence of ileal penetrating complications (defined as abscesses, phlegmones and/or fistula). Demographic, clinical, biochemical, radiological and endoscopic factors were assessed retrospectively in these patients as well as the need for surgery (intestinal resection and/or strictureplasties) and postoperative complications. RESULTS: In total, 1803 cross-sectional imaging exams in 957 CD patients were performed during the study period. In 113 patients, penetrating ileal CD complications were identified. The majority of these patients were referred for surgery (86%) (median time to surgery 1 month, interquartile range: 1-4.9 months). In multivariate analysis, only the presence of abscesses was associated with subsequent surgery (P=0.034; hazard ratio=1.65; 95% confidence interval: 1.04-2.61). Severe postoperative complications (Dindo-Clavien>II) were present in 13% of the patients. Albumin less than 32 g/l was associated with a five-fold increase in severe complications (P=0.039; hazard ratio=4.9; 95% confidence interval: 1-22). Up to 35% of the patients needed no further medical treatment during the first 5 years postoperatively. CONCLUSION: In this cohort, the majority of patients with penetrating ileal CD underwent surgery. The presence of an abscess showed a significant association with the need for surgery. There was an acceptable postoperative complication rate. Patients with low albumin had an unfavourable postoperative course. The long-term outcome after surgery was favourable.

Pressure flow analysis in the assessment of preswallow pharyngeal bolus presence in Dysphagia.

Objectives. Preswallow pharyngeal bolus presence is evident in patients with oropharyngeal dysphagia. Pressure flow analysis (PFA) using high resolution manometry with impedance (HRMI) with AIMplot software is a method for objective interpretation of pharyngeal and upper esophageal sphincter (UES) pressures and bolus flow patterns during swallowing. This study aimed to observe alterations in PFA metrics in the event of preswallow pharyngeal bolus presence as seen on videofluoroscopy (VFSS). Methods. Swallows from 40 broad dysphagia patients and 8 controls were recorded with a HRMI catheter during simultaneous VFSS. Evidence of bolus presence and level reached prior to pharyngeal swallow onset was recorded. AIMPlot software derived automated PFA functional metrics. Results. Patients with bolus movement to the pyriform sinuses had a higher SRI, indicating greater swallow dysfunction. Amongst individual metrics, TNadImp to PeakP was shorter and flow interval longer in patient groups compared to controls. A higher pharyngeal mean impedance and UES mean impedance differentiated the two patient groups. Conclusions. This pilot study identifies specific altered PFA metrics in patients demonstrating preswallow pharyngeal bolus presence to the pyriform sinuses. PFA metrics may be used to guide diagnosis and treatment of patients with oropharyngeal dysphagia and track changes in swallow function over time.

Magnetic resonance imaging of perianal fistulas.

Perianal fistulization is the result of a chronic inflammation of the perianal tissues. A wide spectrum of clinical manifestations, ranging from simple to complex fistulas, can be seen, the latter especially in patients with Crohn disease. Failure to detect secondary tracks and hidden abscesses may lead to therapeutic failure, such as insufficient response to medical treatment and relapse after surgery. Currently, magnetic resonance (MR) imaging is the preferred technique for evaluating perianal fistulas and associated complications. Initially used most often in the preoperative setting, MR imaging now also plays an important role in evaluating the response to medical therapy.

Effects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease.

BACKGROUND AND AIMS: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy. METHODS: In this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5 mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease. RESULTS: Twenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by ≥2 points and by ≥50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index. CONCLUSION: Improvement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare.

Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study.

PURPOSE: Skin toxicity in patients receiving cetuximab has been associated positively with clinical outcome in several tumor types. This study investigated the effect of cetuximab dose escalation in patients with irinotecan-refractory metastatic colorectal cancer who had developed no or mild skin reactions after 21 days of treatment at the standard dose. This article reports clinical and pharmacokinetic (PK) data. PATIENTS AND METHODS: After 21 days of standard-dose cetuximab (400 mg/m(2) initial dose, then 250 mg/m(2) per week) plus irinotecan, patients with ≤ grade 1 skin reactions were randomly assigned to standard-dose (group A) or dose-escalated (to 500 mg/m(2) per week; group B) cetuximab. Patients with ≥ grade 2 skin reactions continued on standard-dose cetuximab plus irinotecan (group C). RESULTS: The intent-to-treat population comprised 157 patients. PK profiles reflected the dose increase and were predictable across the dose range investigated. Weekly cetuximab doses of up to 500 mg/m(2) were well tolerated, and grade 3 and 4 adverse events were generally comparable between treatment groups. Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively). Dose escalation, compared with standard dosing, showed some evidence for improved response rate (30% v 16%, respectively) and disease control rate (70% v 58%, respectively) but no indication of benefit in relation to overall survival. In an exploratory analysis, dose escalation seemed to increase response rate compared with standard dosing in patients with KRAS wild-type but not KRAS mutant tumors. CONCLUSION: Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated. The possible indication for improved efficacy in the dose-escalation group warrants further investigation.

Histology obtained by needle biopsy gives additional information on the prognosis of hepatocellular carcinoma.

AIM: Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner. METHODS: Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α-fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression. RESULTS: Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1-74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86-10.6), which improved predictive performance. No needle tract dissemination was observed. CONCLUSION: Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.

Caroli disease: review of eight cases with emphasis on magnetic resonance imaging features.

BACKGROUND: Caroli disease is a rare congenital disorder characterized by segmental, nonobstructive dilatation of intrahepatic bile ducts. The term Caroli syndrome is used for the association of Caroli disease with congenital hepatic fibrosis. STUDY AIMS: To provide an overview of the clinical presentation and imaging features of Caroli disease and syndrome, with an emphasis on magnetic resonance imaging. PATIENTS AND METHODS: Retrospective analysis of medical records on eight patients in whom a histologic diagnosis of Caroli disease or syndrome had been made. RESULTS: Presenting signs and symptoms were (hepato)splenomegaly, hematemesis and/or melena, cholangitis, jaundice, and recurrent fever. The central dot sign, defined in the literature as a dot or bundle of strong contrast enhancement within dilated intrahepatic ducts, was found in seven cases on various imaging modalities. A 'dot-like structure' was found in one case in which only unenhanced studies were available. There was a tendency toward a right hepatic-lobe predominance. CONCLUSION: There is an overlap between the imaging features of Caroli disease and Caroli syndrome. Our findings support earlier reports that the central dot sign is highly specific for the disease, and that it can be reliably detected by current imaging techniques.

A phase I radiation dose-escalation study to determine the maximal dose of radiotherapy in combination with weekly gemcitabine in patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: The primary objective of this study was to determine the maximum tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with a fixed dose of gemcitabine (300 mg/m2/week) within the same overall treatment time. METHODS: Thirteen patients were included. Gemcitabine 300 mg/m2/week was administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions, escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a total duration kept at 5 weeks. All patients received a dynamic MRI to assess the pancreatic respiratory related movements. Toxicity was scored using the RTOG-EORTC toxicity criteria. RESULTS: Three of six patients experienced an acute dose limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose level tolerated therapy without DLT. The 54 Gy dose level was designated as the MTD and was deemed not suitable for further investigation. Between both dose levels, there was a significant difference in percentage weight loss (p = 0.006) and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs. 51.82 Gy; p = 0.001). CONCLUSION: Accelerated dose escalation to a total dose of 54 Gy with 300 mg/m2/week gemcitabine was not feasible. GI toxicity was the DLT. Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might have been to large. A dose of 45 Gy is recommended. Considering the good patient outcomes, there might be a role for the investigation of a fixed dose of gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline resectable or unresectable non-metastatic locally advanced pancreatic cancer.

Progressive growth of a pelvic collection five years after endovascular aneurysm repair: an atypical presentation of an asymptomatic contained rupture.

We report a case of an unusual and late presentation of an asymptomatic contained rupture after modular stent-graft implantation to treat an aortobiiliac aneurysm. Follow-up computed tomography (CT) scans 4 and 5 years after endovascular aneurysm repair showed a homogeneous, nonenhancing, but clearly growing, pelvic collection. CT-guided drainage of the collection was performed, and cultures of the evacuated brown fluid were negative for any infection. Control CT scan after drainage showed a complete collapse of both the collection and the previously excluded iliac aneurysms. A direct communication between the sterile pelvic collection and the excluded iliac aneurysm was suggested on this CT imaging and confirmed afterwards by surgery. From these imaging and surgical findings, this pelvic collection can be considered as an atypical presentation of an asymptomatic contained rupture of the excluded aneurysm.

Translumbar thrombin embolization of an aortic pseudoaneurysm complicating lumbar disk surgery.

We report a case of translumbar embolization of an aortic pseudoaneurysm complicating lumbar disk surgery. The iatrogenic pseudoaneurysm was initially treated by open repair, but due to failure of this treatment, we opted for direct translumbar thrombin injection under computed tomography (CT) guidance. The patient recovered completely, and follow-up CT scans showed progressive shrinkage of the residual retroperitoneal hematoma. This minimally invasive treatment should be considered in selected cases as a valuable treatment option for pseudoaneurysms that arise from the aorta.