Background The discrimination of mucinous from serous pancreatic cysts and pseudocysts is an important clinical issue. We established an assay to detect different types of carbohydrate containing molecules like glycans and mucins in biological materials and have called it the LeLISA. The method implies a certain specificity since different lectins bind predominantly to certain di -or oligosaccharides that may appear typically on certain cell types or, as a consequence of cell transformations often called aberrant mucin expression. The presence, or absence of reactivity with some lectins may be associated with different pathological conditions and may therefore have diagnostic implications, for instance in differentiation of pancreatic cysts. We aimed at detecting mucin-calprotectin (Cp)complexes (Muc/Cp) bound to lectin (Le) coated wells using enzyme labelled anti-Cp. Materials and methods The LeLISA is a special type of ELISA where the catching antibody is replaced by a Le. Eight different randomly selected lectins were used for coating of microwells and subsequently incubated with pancreatic cyst fluids collected via endoscopic ultrasound fine needle aspiration (EUS-FNA) from patients with mucinous, serous cysts and pseudocysts, 10 patients in each group. The diagnosis was confirmed through histopathological examination of surgical specimens and follow-up after initial diagnosis. The binding of Muc/Cp to lectins was demonstrated by a new type of ELISA where cyst fluids were incubated in microwells coated with different types of lectins followed by enzyme (HRP) labelled monoclonal anti-Cp. The name LeLISA was introduced for this new procedure. Results Muc/Cpin cyst fluids bound to several of the eight lectins tested, in particular to Galanthus nivalis, Agaricus blazei Murill and Phaseolus vulgaris . This was especially noticeable for fluids from mucin-producing cysts. Conclusions Cyst fluids contain complexes with Cp and mucins. The LeLISA may be a new method for detection of aberrant mucin expression and possibly a way of discriminating between different types of pancreatic cysts, in particular when the Galanthus lectin and enzyme labelled anti-Cp monoclonals are used. The binding to lectins depends upon certain carbohydrate sequences recognized by the individual lectin.
Background Dysplasia and superficial esophageal cancer should initially be treated endoscopically. Little is known about post-procedural health-related quality of life (HRQL). The aim of this study was to present our results with endoscopic treatment and post-procedural HRQL. Materials and methods From June 2014 to December 2018, all patients treated with endoscopic mucosal resection (EMR) and/or radiofrequency ablation (RFA) for low-grade dysplasia (LGD), high-grade dysplasia (HGD), T1a and a minority of patients with T1b at Oslo University Hospital were prospectively included. In June 2019, all patients alive were scored according to the Ogilvie dysphagia score as well as the QLQ-C30 and QLQ-OG25 for assessment of HRQL. Results Eighty-six patients were treated out of whom 22 (26%) had LGD, 44 (51%) HGD, 13 (15%) T1a, and six patients (7%) T1b. Histology revealed adenocarcinoma in 18 (21%) and squamous cell carcinoma in one (1%), respectively. The mean follow-up was 22.9 months. Tumor regression or downstaging was archived in 78% of the patients with LGD, 66% of patients with HGD and in 89% of patients with T1a/b. Five patients (6%) had esophagectomy. There were few and no serious complications. The 90-days mortality was 1%. Fifty-two patients (88%) experienced no dysphagia (Ogilvie score 0). There was no difference in 11 out of the 15 variables in QLQ-C30 when compared to a non-cancerous reference population. Conclusions Endoscopic treatment is safe and efficient for treatment of dysplasia and superficial esophageal cancer. The two-years post-procedural level of HRQL and dysphagia was satisfactory.
Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.
Introduction Chemotherapy has been shown to improve survival in patients with locally advanced and metastatic cholangiocarcinoma (CC). Similar data have been reported with photodynamic therapy (PDT) in combination with stent drainage. A combination of these treatment modalities might improve outcomes further, but such data are still lacking. Therefore we have performed the first randomized trial on the combination of temoporfin/PDT, stent and chemotherapy versus stent and chemotherapy only. Methods Randomized phase II trial with feasibility and toxicity as endpoints. Preliminary data on progression free survival will also be reported. Inclusion criteria were unresectable, treatment naive patients with CC confirmed by histology or cytology, need for biliary stent, bilirubin level Results Twenty patients with locally advanced and metastatic disease were included, ten patients in each arm. Eight men and twelve women, age 35-75 years. Two patients in arm A did not receive chemotherapy (ECOG>2, infection) and two patients in arm B (thrombocytopenia, study withdrawal). No serious, procedure-related complication was seen. Three cases of cholangitis were observed in both group A and B during the first 30 days. Within the next two months three additional patients in each group had cholangitis, grade 3-4. No liver abscess was observed within 30 days. Within three months, liver abscess was found in two patients, group A. Neutropenia grade 3 was observed in 2 patients in both arms, no neutropenic infection. Preliminary data on progression free survival (three still without progression, one just started) were mean 212 days in group A compared to 162 days in group B. Data on QoL will be reported. Conclusion The total number of cholangitis was equal in both groups, two abscesses were seen only in group A, more than one month after PDT. No other serious complication related to PDT was seen. Preliminary, progression free survival seems to be prolonged in group A. Depending on the final data a larger study should be considered.
e14637 Background: Patients whocannot be offered curative surgical treatment for biliary tract cancer (BTC) have a poor prognosis. Photodynamic therapy (PDT) has been shown to improve survival and quality of life in patients with unresectable BTC. A combination of treatment modalities might improve survival further, but such data are still lacking. Therefore we have performed the first randomized trial on the combination of temoporfin/PDT and chemotherapy. Here we report data on the feasibility and safety. Methods: Randomized phase II trial, planned to include 20 patients with time to progression as primary endpoint, feasibility and toxicity as secondary endpoints. Inclusion criteria were unresectable BTC confirmed by histology or cytology, need for biliary stent, bilirubin level < 50 mmol/L and no previous cancer disease. The treatment arms were: A: Stent, temoporfin / PDT followed by gemcitabin / capecitabin (GemCap). B: Stent, GemCap. Only one initial PDT treatment was given. Results: Twenty patients with locally advanced and metastatic disease were included, 10 patients in each arm. Two patients in arm B did not receive any treatment (thrombocytopenia, study withdrawal) and two patients in arm A did not receive chemotherapy (ECOG>2, infection). PDT was feasible in all 10 patients without any acute procedure-related complication. During the first 30 days, two cases of cholangitis in arm A and three in arm B were observed. Cutaneous erythema (grade 1-2) was observed after PDT in two patients. Conclusions: PDT using temoporfin in combination with chemotherapy in BTC was feasible. Restrictions to light exposure were well tolerated. PDT in combination with chemotherapy did not increase the complication rate during the first 30 days follow-up. Three months follow-up data will be available at the time for presentation. Larger prospective trials are warranted to assess the efficacy of this treatment combination.