Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2):study protocol for an international multicenter patient-blinded randomized controlled trial

Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023.</p

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis : a cross-sectional multicentre international study with experimental animal model

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n=983), recurrent AP (RAP, n=270) and CP (n=62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5+was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3+do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.Peer reviewe

Outcomes After Minimally-invasive Versus Open Pancreatoduodenectomy: A Pan-European Propensity Score Matched Study

OBJECTIVE: To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers. BACKGROUND: Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking. METHODS: Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3). RESULTS: Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF (24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001). CONCLUSIONS: In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed

The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy

The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy

Russian consensus on exoand endocrine pancreatic insufficiency after surgical treatment

The Russian consensus on exo - and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo - and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.</p

Прогнозирование панкреатической фистулы после панкреатодуоденальной резекции с помощью компьютерной томографии

Aim. To reveal and evaluate opportunities of preoperative computer tomography (CT) for pancreatic fistula (PF) prediction after pancreatoduodenectomy.Materials and methods. In 2005 International Study Group on Pancreatic Fistula (ISGPF) developed grading criteria for PF, including asymptomatic biochemical (Grade A), that could be treated conservatively, and clinically relevant (Grade B, Grade C), with consecutive active surgical treatment. For now ISGPF definition of PF is widely accepted. We review the literature since 2005 for original articles in English describing quantitive assessment of the pancreatic parenchyma using CT with histological validation. Low sample trials (&lt;10 cases) were excluded.Results. Three original publications met the inclusion criteria. Fatty and fibrosis infiltration of the pancreatic parenchyma assessed by preoperative CT revealed statistically significant correlation with PF rate.Conclusion. Preoperative CT offers accurate prediction opportunities for postoperative pancreatic fistula and may help caregivers to set up protocols for a strict and early detection of warning clinical signs, to tailor the clinical management of different risk classes, or to select high-risk patients who might be excluded from surgical resection. This would also improve patient selection for relevant research protocols and facilitate a more definitive assessment of collected data related to surgical outcomes, across different institutions and surgeons, and even among different surgeries, in either single-institution or multi-center trials that involve pancreatic surgery.Цель исследования: выявить и оценить возможности прогнозирования панкреатической фистулы после панкреатодуоденальной резекции на основании данных предоперационной компьютерной томографии (КТ).Материал и методы. В 2005 г. Международная рабочая группа по изучению панкреатических фистул (International Study Group on Pancreatic Fistula, ISGPF) разработала критерии градации панкреатических фистул на бессимптомные биохимические (Grade A) и клинически значимые (Grade B и С), требующие терапевтической (Grade A) или хирургической коррекции (Grade B и С). Данная классификация стала общепринятой и широко используется. Проведен анализ литературы, при котором учитывались только оригинальные англоязычные публикации после 2005 г, которые описывали возможности предоперационной количественной оценки плотности поджелудочной железы (ПЖ) с помощью КТ, а данные КТ сопоставлялись с результатами гистологического исследования ткани ПЖ. Работы с малыми выборками (&lt;10 пациентов) были исключены из анализа.Результаты. Критериям включения соответствовали 3 статьи, описывающие возможности КТ для оценки степени фиброза и жировой инфильтрации паренхимы ПЖ, в качестве факторов риска панкреатической фистулы. Выявлена статистически достоверная зависимость данных показателей и риска панкреатической фистулы.Заключение. Современные возможности Кт позволяют объективно судить о риске развития панкреатической фистулы и предоставляют хирургам возможность подобрать наиболее подходящую периоперационную тактику ведения пациента. Прогнозирование риска панкреатической фистулы и формирование гомогенных групп для клинических исследований позволят получать более достоверные результаты при анализе данных даже из разных источников, что, несомненно, повысит качество проводимых исследований

Злокачественное новообразование молочной железы в составе синдрома Коудена

Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85 %, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer.Objective: To demonstrate the non‑BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example.Materials and methods: The article describes a clinical case of a 37‑year‑old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes.Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome.Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.Синдром Коудена характеризуется наличием множественных гамартом с высоким риском развития доброкачественных и злокачественных опухолей щитовидной железы, молочной железы, почек и эндометрия. Риск развития рака молочной железы у пациентов с синдромом Коудена в течение жизни составляет 85 %, при этом средний возраст постановки диагноза составляет от 38 до 46 лет. Диагностические критерии синдрома Коудена установлены Международным консорциумом по синдрому Коудена (ICC) и Американской ассоциацией онкологов (NCCN) и подвергаются регулярному пересмотру, однако диагностика синдрома Коудена по‑прежнему затруднена ввиду разнообразия фенотипических особенностей и клинических признаков заболеваний. В то же время, анализ генетических вариантов, ассоциированных с синдромом Коудена, не является стандартом обследования при диагностике рака молочной железы.Цель: продемонстрировать выявление методом полногеномного секвенирования наследственных опухолевых синдромов, клиническим проявлением которых могут быть злокачественные новообразования молочной железы, на примере синдрома Коудена.Материалы и методы: в статье описан клинический случай пациентки 37 лет с нормальным интеллектом и фенотипом, структурными поражениями щитовидной железы (многоузловой зоб), обратившейся по поводу рака молочной железы. В рамках научного исследования с целью выявления клинически значимых генетических вариантов, ассоциированных с наследственными опухолевыми синдромами, применен метод полногеномного секвенирования.Клинический случай: в статье представлен краткий обзор литературы, посвященный клинической характеристике синдрома Коудена, и показаний для молекулярной диагностики. Описан клинический случай пациентки Р., 37 лет, которая проходила лечение в ГБУЗ «Городская клиническая онкологическая больница № 1 ДЗМ» в 2021 г. по поводу рака молочной железы. С учетом диагностированного в возрасте до 50 лет злокачественного новообразования молочной железы пациентка включена в научный проект по проведению полногеномных исследований в рамках приказа Департамента Здравоохранения г. Москвы № 69 от 01.02.2021 «Об организации проведения онкогенетических исследований в городе Москве», по результатам генетического исследования выявлен патогенный вариант гена PTEN, ассоциированный с синдромом Коудена.Вывод: Применение полногеномного секвенирования позволяет выявлять наследственные опухолевые синдромы, клиническим проявлением которых могут быть злокачественные новообразования молочной железы