Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC)

Background According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers EudraCT 2019–002734-37; NCT04617457.

Differential Diagnostics Focal Pancreatics Masses Based on the Analysis of the Echographic Texture of Endosonograms Using Fuzzy Mathematical Models

Relevance: Differential diagnosis of focal formations of the pancreas is particularly difficult due to the similarity of their echosemiotics. One of the ways to objectify and improve the accuracy of ultrasound data is to use artificial intelligence methods to interpret images.Purpose: Improving the quality of diagnosis of focal pancreatic pathology according to endoscopic ultrasonography based on the analysis of the echographic texture using fuzzy mathematical models.Material and methods: In the Kursk Regional Clinical Hospital, endoscopic ultrasonography was performed in 272 patients for pancreaticobiliary diseases. The endoscopic video system of the company Olympus EVIS EXERA II with the ultrasonic processor EU-ME1 was used. Solid tumors of the pancreas were detected in 109 (40.1 %) patients, focal pancreatic masses were diagnosed in 40 (14.7 %) patients. Based on the research results, the main types of reference endosonograms corresponding to differentiable pathology were identified. On the basis of endosonograms, using hybrid fuzzy mathematical decision rul, a fuzzy hybrid model of differential diagnosis of chronic focal pancreatitis and ductal adenocarcinoma of the pancreas was obtained.Results: The selected source of information and the method of synthesis of hybrid fuzzy decision rules made it possible to obtain a fuzzy hybrid model of differential diagnosis of chronic focal pancreatitis and ductal adenocarcinoma of the pancreas. Based on the results of mathematical modeling and statistical tests on representative control samples, it was shown that the resulting model of differential diagnosis, using reference endosonograms reflecting the echographic texture of focal pancreatic masses, provides confidence in the desired diagnosis at the level of 0.6. The additional information used in the analysis of endosonograms increases the diagnostic confidence to a value of 0.9.Conclusions: The resulting model of differential diagnosis of chronic focal pancreatitis and ductal adenocarcinoma of the pancreas provides confidence in decision-making no worse than 0.9, which is an acceptable quality indicator in clinical practice in conditions of insufficient statistics with poorly formalized data structure.

Clostridium difficile Infection Leading to Intestinal Pneumatosis in a Patient with a Recent Diagnosis of Pancreatic Cancer Local Recurrence: A Case Report and Literature Review

<i>Clostridium difficile</i> infection (CDI) causing pneumatosis intestinalis (PI) is a rare event, described mostly in immunocompromised patients. We present the case of a 65-year-old female diagnosed with adenocarcinoma of the pancreas who underwent a duodenopancreatectomy with lymphadenectomy and adjuvant gemcitabine and capecitabine. Four months after the end of chemotherapy, she experienced abdominal pain and intermittent diarrhea which became aggravated within 6 months. CT scans revealed diffuse intestinal pneumatosis and recurrence of ductal adenocarcinoma. We hypothesize that local pancreatic cancer recurrence may lead to gastrointestinal dysmotility with consequent increased risk for CDI. The patient had almost complete resolution of PI during the CDI treatment, thus we believe that the CDI was directly responsible for PI in this case.

The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.

e16272 Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.

Association between Low-Grade Chemotherapy-Induced Peripheral Neuropathy (CINP) and Survival in Patients with Metastatic Adenocarcinoma of the Pancreas

The combination of nab-paclitaxel and gemcitabine demonstrated greater efficacy than gemcitabine alone but resulted in higher rates of chemotherapy-induced peripheral neuropathy (CINP) in patients with metastatic pancreatic cancer (mPC). We aimed to evaluate the correlation between the development of treatment-related peripheral neuropathy and the efficacy of nab-P/Gem combination in these patients. mPC patients treated with nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 as a first-line therapy were included. Treatment-related adverse events, mainly peripheral neuropathy, were categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02. Efficacy outcomes, including overall survival (OS), progression-free survival (PSF), and disease control rate (DCR), were estimated by the Kaplan–Meier model. A total of 153 patients were analyzed; of these, 47 patients (30.7%) developed grade 1–2 neuropathy. PFS was 7 months (95% CI (6–7 months)) for patients with grade 1–2 neuropathy and 6 months (95% CI (5–6 months)) for patients without peripheral neuropathy (p = 0.42). Median OS was 13 months (95% CI (10–18 months)) and 10 months (95% CI (8–13 months)) in patients with and without peripheral neuropathy, respectively (p = 0.04). DCR was achieved by 83% of patients with grade 1–2 neuropathy and by 58% of patients without neuropathy (p = 0.03). In the multivariate analysis, grade 1–2 neuropathy was independently associated with OS (HR 0.65; 95% CI, 0.45–0.98; p = 0.03). nab-P/Gem represents an optimal first-line treatment for mPC patients. Among possible treatment-related adverse events, peripheral neuropathy is the most frequent, with different grades and incidence. Our study suggests that patients experiencing CINP may have a more favorable outcome, with a higher disease control rate and prolonged median survival compared to those without neuropathy.

DIFFERENTIAL DIAGNOSIS OF PANCREATIC PATHOLOGY ACCORDING TO ENDOSCOPIC ULTRASONOGRAPHY BASED ON FUZZY MATHEMATICAL MODELS

Эндоскопическая ультрасонография, являясь высокоинформативным и уточняющим методом диагностики патологии поджелудочной железы остается в значительной мере субъективным и операторзависимым исследованием. Целью работы явилось повышение качества дифференциальной диагностики очаговой патологии поджелудочной железы на основе анализа эталонных эндосонограмм за счет использования гибридных нечетких математических моделей, при синтезе которых формальные процедуры строятся с использованием клинического опыта высококвалифицированных специалистов ультразвуковой диагностики. В отделении эндоскопии Курской областной клинической больницы эндоскопическая ультрасонография выполнена у 729 пациентов. Опухоли поджелудочной железы выявлены у 139 (19,1%) пациентов, различные формы хронического панкреатита диагностированы у 141 (19,3%) больного. По результатам исследований выделены 6 типов эталонных эндосонограмм, соответствующих дифференцируемой патологии, на основании которых, с использованием гибридных нечетких математических решающих правил, разработанных в Юго-Западном государственном университете, получена нечеткая гибридная модель дифференциальной диагностики хронического очагового панкреатита и протоковой аденокарциномы поджелудочной железы. По результатам математического моделирования и статистических испытаний на репрезентативных контрольных выборках было показано, что полученная модель дифференциальной диагностики, использующая только эталонные эндосонограммы, обеспечивает уверенность в искомом диагнозе на уровне 0,6. Дополнительная информация, получаемая при анализе эндосонограмм, повышает диагностическую уверенность до величины 0,9. Таким образом, полученная модель дифференциальной диагностики хронического очагового панкреатита и протоковой аденокарциномы поджелудочной железы обеспечивает приемлемое для клинической практики качество принимаемых решений Endoscopic ultrasonography is a highly informative and clarifying method for diagnosing pancreatic pathology. At the same time, it remains to a large extent subjective and operator-dependent research. The aim of this work is to improve the quality of differential diagnosis of focal pancreatic pathology based on the analysis of reference endosonograms through the use of hybrid fuzzy mathematical models. When synthesizing these models, formal procedures are built using the clinical experience of highly qualified specialists in ultrasound diagnostics. In the endoscopy department of the Kursk Regional Clinical Hospital, endoscopic ultrasonography was performed in 729 patients. Pancreatic tumors were detected in 139 (19.1%) patients, various forms of chronic pancreatitis were diagnosed in 141 (19.3%) patients. Based on the research results, 6 types of reference endosonograms corresponding to differentiable pathology were identified. On the basis of endosonograms, using hybrid fuzzy mathematical decision rules developed at Southwestern State University, a fuzzy hybrid model of differential diagnosis of chronic focal pancreatitis and ductal adenocarcinoma of the pancreas was obtained. Based on the results of mathematical modeling and statistical tests on representative control samples, it was shown that the resulting model of differential diagnosis, using only reference endosonograms, provides confidence in the desired diagnosis at the level of 0.6. Additional information obtained from the analysis of endosonograms increases the diagnostic confidence to a value of 0.9. Thus, the model obtained for the differential diagnosis of chronic focal pancreatitis and ductal adenocarcinoma of the pancreas provides an acceptable quality of decisions for clinical practice

CT Simplified Radiomic Approach to Assess the Metastatic Ductal Adenocarcinoma of the Pancreas

The aim of this study was to perform a simplified radiomic analysis of pancreatic ductal adenocarcinoma based on qualitative and quantitative tumor features and to compare the results between metastatic and non-metastatic patients. A search of our radiological, surgical, and pathological databases identified 1218 patients with a newly diagnosed pancreatic ductal adenocarcinoma who were referred to our Institution between January 2014 and December 2018. Computed Tomography (CT) examinations were reviewed analyzing qualitative and quantitative features. Two hundred eighty-eight patients fulfilled the inclusion criteria and were included in this study. Overall, metastases were present at diagnosis in 86/288 patients, while no metastases were identified in 202/288 patients. Ill-defined margins and a hypodense appearance on portal-phase images were significantly more common among patients with metastases compared to non-metastatic patients (p < 0.05). Metastatic tumors showed a significantly larger size and significantly lower arterial index, perfusion index, and permeability index compared to non-metastatic tumors (p < 0.05). In the management of pancreatic ductal adenocarcinoma, early detection and correct staging are key elements. The study of computerized tomography characteristics of pancreatic ductal adenocarcinoma showed substantial differences, both qualitative and quantitative, between metastatic and non-metastatic disease.