Lesions Of Pancreas Research Articles

8604 Ectopic Cushing’s Syndrome Associated with a Metastatic Pancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasm (MiNEN) with Amphicrine Features

Abstract Disclosure: A. DeMarsilis: None. C. Jiang: None. O. Lavrynenko: None. D. Motavalli: None. C. Musurakis: None. Z.H. Taxin: None. E.D. Rosen: Advisory Board Member; Self; Source Bio, Inc.. Consulting Fee; Self; Novartis Pharmaceuticals, Gensaic. M.S. Irwig: None. Background: Ectopic Cushing’s Syndrome (CS) makes up 9-18% of ACTH-dependent CS cases, of which fewer than 15% are attributed to pancreatic neuroendocrine tumors (1). Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare, aggressive carcinomas, often driven by high-grade neuroendocrine components, with a poor prognosis (2). Amphicrine neoplasms contain neuroendocrine and exocrine components in the same cell. Clinical Case: A 34 year-old woman with asthma, hypertension, and depression presented with new onset lower extremity edema, facial hirsutism, mood changes, polyuria and polydipsia. She had an elevated morning serum cortisol of 52 ug/dL (normal < 20) with plasma ACTH 42 pg/mL (normal < 50), 24-hour urine free cortisol of 1003 mcg (normal < 50), K+ of 2.6 mEq/L, and fasting glucose 164 mg/dL. CT showed multiple hepatic lesions, pulmonary nodules, a pancreatic tail lesion, and lymphadenopathy concerning for metastatic disease. Her adrenal glands were thickened bilaterally without nodules. A pituitary MRI was normal. These findings were concerning for ectopic CS. She was admitted due to rapidly developing symptoms. Potassium, insulin, sitagliptin, and prophylactic anticoagulation were started. Spironolactone and ketoconazole were initiated while awaiting biopsy results of liver and pancreas lesions. Osilodrostat was not available and a trial of metyrapone was poorly tolerated. The liver and pancreatic tail lesion biopsy revealed metastatic MiNEN with amphicrine features, of pancreatic origin, with Ki67 proliferation index of 70%. Section staining of pancreas and liver biopsies were negative for ACTH. A Ga-68 Dotatate scan showed minimal uptake, so octreotide was not prescribed. Palliative chemotherapy was planned. Although ketoconazole was titrated to 1600 mg/day, urine free cortisol levels and serum free cortisol levels did not reach target. Cushing disease was considered but not suspected, as ACTH levels remained modest despite a relative decrease in cortisol level. Given significant morbidity from uncontrolled hypercortisolism, and plans for urgent initiation of systemic chemotherapy, after multidisciplinary discussion the patient was treated with a surgical bilateral adrenalectomy. Post-operative morning serum cortisol measured 8.3 ug/dL. After one week, palliative chemotherapy with FOLFIRINOX (oxaliplatin, leucovorin, fluorouracil, and irinotecan) was initiated. She was discharged home on stress dose steroids with plan for taper. Conclusion: Ectopic ACTH secretion is a rare phenomenon, particularly when presenting with a rare case of metastatic pancreatic MiNEN with amphicrine features, associated with significant morbidity. To improve tolerance and survival of further treatment, early surgical bilateral adrenalectomy should be considered.

Review of spontaneous lesions in the exocrine pancreas of domestic ferrets (Mustela furo).

Large-scale retrospective studies allow for identification of disease trends, such as predisposing factors, typical clinical signs, and range of histologic lesions, which cannot be determined in individual case reports. Lesions of the endocrine pancreas of ferrets are extensively reported; however, there are no in-depth investigations of lesions in the exocrine pancreas. This retrospective analysis presents the histologic features, clinical signs, and concurrent diseases of lesions in the exocrine pancreas of ferrets. Seventy-seven lesions were reported and included acinar cell hyperplasia (n = 32), chronic pancreatitis (n = 16), acute pancreatitis (n = 13), acinar cell adenoma (n = 5), acinar cell carcinoma (n = 4), acinar cell atrophy (n = 3), presumptive acinar cell hypoplasia (n = 2), and lymphoma (n = 2). Our results demonstrate that acinar cell hyperplasia and chronic pancreatitis can both cause grossly visible pancreatic nodules. Hyperplasia was not associated with neoplastic transformation. In addition, acinar cell adenoma was slightly more common than carcinoma, which is contrary to most reports of neoplasia in ferrets. Our findings also suggest that acute pancreatitis can be a sequela to pancreatic biopsy and that there may be an association between chronic pancreatitis and diabetes mellitus in ferrets. Finally, zinc toxicosis was found to be an unlikely cause of pancreatitis in these ferrets based on zinc tissue concentration testing in a subset of cases.

Robotic Spleen-Preserving Distal Pancreatectomy: The Warshaw and Kimura Techniques.

Spleen-preserving distal pancreatectomy offers an alternative surgical approach to the traditional distal pancreatectomy combined with splenectomy for removing benign and low-grade malignant lesions in the distal pancreas, avoiding complications associated with splenectomy. This procedure can be accomplished either by resecting and ligating the splenic vessels (Warshaw technique) or by preserving them (Kimura technique). Currently, the widespread use of minimally invasive surgery has established laparoscopic and robotic approaches for spleen-preserving distal pancreatectomy as valid and safe options for treating such conditions. Our protocol aims to describe how the Warshaw and Kimura techniques of spleen-preserving distal pancreatectomy can be performed robotically. The first patient is a 36-year-old female with a neuroendocrine tumor (NET) in the pancreatic body who underwent a spleen-preserving distal pancreatectomy with the ligation of the splenic vessels (WT). The second patient is a 76-year-old male with chronic pancreatitis presenting with a dilated main pancreatic duct in the tail of the pancreas who underwent a spleen-preserving distal pancreatectomy with a vessel-preserving approach (KT).

Anatomical and demographic prognosticators of pancreatic cancer.

e16310 Background: Pancreatic cancer is known to have one of the poorest median of survival (mOS) of all cancers. It is now the third leading cause of cancer-related mortality after lung & colorectal cancer. With the current trends, understanding & knowing prognosticators can aid in determining outcomes of pancreatic cancer. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted pancreatic cancer cases based on primary site encoding for head, body & tail of pancreas, Islets of Langerhans (IoL), other specified parts & overlapping lesion of pancreas, pancreas, NOS (no other specific). The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 221,304 cases were extracted between 2000-2020. The median age of diagnosis was 71 years. 50.54% were males, & 49.45% were females. The incidence rates are shown below. Whites (69.99%) were commonly affected, followed by Blacks (11.05%), Hispanics (10.79%), Asians & Pacific islanders (7.41%), Alaskan natives & American-Indians (0.57%). A distribution in anatomy was notable for head of the pancreas (46.00%), followed by tail (13.20%), body (11.34%), pancreatic duct (0.49%), IoL (0.10%). A survival curves were compared on different variables. Gender showed no statistical difference. mOS for patients diagnosed >70 years was 3 months & <70 years was 8 months (p value <0.0001, CI 0.3716 to 0.3784, HR 1.731). mOS for calculated for Whites (5), Blacks (4), Asian & Pacific islanders (6), Alaskan natives & American-Indians (4), & hispanics (5) (p value <0.0001). mOS based on involved parts of pancreas were compared for: head (6), body (6), tail (5), pancreatic duct (8), IoL (59) (p <0.0001). Conclusions: Median age of diagnosis was in 71, with a slight male predilection. Overall incidence rate is trending up. It is significantly higher for males, & is significantly lower for females than that of the general population. Whites are most commonly affected, & Alaskan natives & American natives are rarely affected. Survival is significantly greater if diagnosed <70 years. Most common site involved is the head of pancreas, & the least is IoL. mOS is ~10 times greater for IoL, but it's an endocrine pancreatic cancer which is treated differently. From the exocrine pancreas, survival is the best for pancreatic duct cancer, & the worst for pancreatic duct. If anatomic & demographic prognosticators are combined with molecular, radiologic factors, it can be beneficial in predicting the outcomes of this cancer with poor prognosis. [Table: see text]

Abstract 1074: Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer

Abstract The lack of reliable biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis due to advanced disease at diagnosis. Biopsies for pancreatic cancer are known to be particularly difficult to perform because of the location of the pancreas and low volume of primary tumors that metastasize aggressively. Currently, there is no blood test or other screening modality in use, for stratification of individuals with higher-than-average risk (5-8-fold) of developing PDAC in their lifetime. Given this existing void in the US and worldwide, an FDA-compliant, minimally invasive, quantitative biomarker test for the early detection of PDAC would be critical for screening subpopulations with, a) inherent genetic or familial predisposition; history of chronic pancreatitis; c) precursor lesions of pancreas; and d) older patients (>50 years) with new onset diabetes or sudden weight loss. Extracellular vesicles (EVs) are shed by normal and cancer cells and carry a rich molecular cargo that can be leveraged for biomarker discovery. Whereas molecular profiling of bio-fluids poses intrinsic limitations for detection of low abundant, disease-specific biomarkers due to matrix effects; EVs, on the other hand, offer promise as a robust and minimally invasive biomarker resource. Mass spectrometry data were developed in our laboratory, based on multi-omics (proteomics, lipidomics and metabolomics) analyses of plasma EVs derived from patients diagnosed with early-stage PC (N=60), pancreatitis (N=39), precursor lesions of pancreas (N=45) as well as normal controls (N=50). These clinically annotated samples were made available by the Georgetown University Medical Center (GUMC) repository. Feature selection using a training-validation design allowed the development of a multiplexed biomarker panel comprising of 12-analytes (5-lipids, 2-metabolites and 5-proteins) that can robustly stratify early-stage PC from normal controls with high accuracy (AUC>95%). Availability of a FDA compliant, multi-analyte-based classification algorithm that can stratify patients with precursor lesions of the pancreas that are at potential risk of progression to PC with > 90% specificity and sensitivity is a critical clinical need. Refinement of panel to improve positive predictive value as well as identification of markers predictive of progression of precursor lesions to malignant transformation is ongoing. Citation Format: Shivani Bansal, Shu Wang, Yaoxiang Li, Sunil Bansal, Jill Smith, John B. Tyburski, Keith Unger, Amrita Cheema. Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1074.

Abstract B068: Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer

Abstract The traditional cancer paradigm, in which radiographic scan precedes biopsy which precedes diagnosis, has several limitations, but lack of patient identification prior to biopsy lies at the crux. Here we describe the results of our retrospective pilot study, in which we characterize the output of a natural language processing (NLP) model we utilized to review and flag radiology reports suspicious for pancreas cancer and demonstrate its potential for identification of patients with pancreas cancer at earlier points in the diagnostic framework. A RadBERT based NLP model was utilized to identify radiology reports suspicious for pancreas cancer that were generated within the Northwell Health system in January 2023. These outputs were then manually reviewed retrospectively and labelled as non-suspicious non-cystic, non-suspicious cystic, or suspicious non-cystic. For patients with suspicious non-cystic lesions, chart review was performed to determine whether these findings were indicative of a new pancreatic malignancy, and if so, whether the patient had received further care. Our NLP reviewed 17,339 radiology reports in January 2023 and identified 917 of these reports as suspicious for pancreas cancer, representing imaging from 852 patients across our health system. 38% of patients had normal or atypical but non-suspicious non-cystic lesions (322). 46% of patients had non-suspicious cystic lesions (389) and 17% of patients had suspicious non-cystic lesions suspicious for a primary pancreatic neoplasm (149); 10 of these reports observed simultaneous cystic and neoplastic pancreas lesions. Of the patients with suspected neoplastic lesions, 55% had been previously diagnosed with pancreas cancer. 45% were new diagnoses and upon chart review, of these, only 36% underwent biopsy in our health system with an average of 22 days between radiology report and biopsy while 30% were seen by an outpatient oncologist within our health system with an average of 32 days between radiology report and visit. 64% did not proceed to further workup in our health system with 35% for whom further workup was not recommended, 19% who elected against further workup, 23% who were scheduled for internal follow-up that did not occur, and 23% who were scheduled for external follow-up. Notably, when compared to the January outputs of other cohort building tools, NLP identified 67 new patients with pancreas cancer, while pathology report identified 15, ICD10 problem list identified 17, and cancer registry identified 13. Our NLP approach identified the greatest proportion of patients with newly diagnosed pancreas cancer compared to traditional identification measures and of these patients identified by our model, in the context of the traditional cancer care paradigm, only 1/3 proceeded to further workup within our health system before facing a striking nearly month of lead-time between radiology report and biopsy/outpatient oncology visit. We are now working to leverage this model to prospectively identify and navigate patients identified by NLP to address this gap in real-time. Citation Format: Kristen M. John, Anthony Carvino, Shama Khan, Ellen Chen, Deepak Saluja, Matthew Barish, Daniel A. King. Retrospective pilot study of a natural language processing model approach for earlier identification of patients with pancreas cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B068.

Abstract C104: Dual primary pancreas cancers – Related or independent lesions?

Abstract Background: Not infrequently, an apparent second pancreas ductal adenocarcinoma (PDAC) is identified either synchronously or metachronously. To date, it remains unclear whether these individual PDACs represent intrapancreatic metastases or a new primary PDAC. Here, we sought to understand the clinicogenomic features of this patient population to provide insights on the underlying biology and management implications. Methods: Memorial Sloan Kettering Cancer Center (MSK) institutional databases were searched for patients with two PDAC diagnoses and at least one pancreatic resection or patients who had undergone completion/total pancreatectomy and then manually curated. Detailed demographic and clinical information were abstracted from the medical record. Metachronous patients excluded if previous surgical margin positive for invasive or pre-invasive carcinoma. All patients were either consented to MSK IMPACT for somatic and germline sequencing (N=16), were approved for de-identified genomic analyses by IRB (N=3), or were excluded from genomic analysis (N=2). KRAS wild-type (WT) tumors were interrogated for targetable fusions with Archer FusionPlex solid tumor panel. Results: N=21 patients (pts) identified, N=6 synchronous, N=15 metachronous. Mean age at diagnosis of first PDAC (PDAC1): 67.1y (51.2–79.1y). PDAC risk factors: 52% (10/19) smoking history, 15% (2/13) with first degree relative with PDAC, 85% (11/13) with first degree relative with any malignancy, and 40% (8/20) with history of premalignant pancreas lesion. N=2 pts with pathogenic germline mutation in ATM. By morphology, 80% (4/5) of synchronous and 65% (11/17) of asynchronous lesions indistinguishable. Two lesions, both metachronous, demonstrated divergent histology while remaining cases demonstrated focal differences. Genomically, 40% (10/25) samples with mKRAS G12V, G12R (16%), G12D (12%), Q61H (8%), G12C (4%); 20% KRAS WT. Of available paired tumor samples, 71% (5/7) with identical KRAS alleles and additional driver mutations. N= 1 pt with different KRAS alleles also had divergent TP53 alleles and CDKN2A/B loss occur in metachronous lesions 14 m apart. N=1 pt with KRAS WT tumor had an actionable fusion involving FGFR2. For metachronous lesions, median interval PDAC1 to PDAC2: 5.1 y (1.1 – 15.2 y). At median follow-up of 7.2 y (0.2 – 15.4 y) from PDAC1, 90% (19/21) have undergone completion/total pancreatectomy and N=16 (76%) alive with 5-year survival rate of 93% (14/15). Conclusions: The clinical, pathologic, and genomic data strongly suggest that two PDAC, independent of disease interval, most often represent the same phylogenetic entity. KRAS allele variant adjudication was the single most important discriminator and was in concordance with other driver oncogenes. Pathogenic germline variants were rare and limited to gATM; notably no gBRCA/PALB2. Acknowledging the highly selected nature of this cohort, solitary intrapancreatic metastases demonstrate a more favorable biology and these patients may benefit from personalized management approaches beyond traditional paradigms. Citation Format: Joshua D. Schoenfeld, Hulya Sahan-Ozkan, Nadeem Bilani, Michael I. D'Angelica, William R. Jarnagin, Jeffrey Drebin, Diane Reidy-Lagunes, Alice C. Wei, Sree B. Chalasani, Anna M. Varghese, Fiyinfolu Balogun, Wungki Park, Kenneth H. Yu, Olca Basturk, Eileen M. O'Reilly. Dual primary pancreas cancers – Related or independent lesions? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C104.

Autogenic splenic implantation versus splenectomy in patients undergoing distal pancreatectomy for benign or low-grade malignant lesions of the distal pancreas: study protocol for a multicentre, open-label, randomized controlled trial (RESTORE)

BackgroundThe spleen plays a significant role in the clearance of circulating microorganisms. Sequelae of splenectomy, especially immunodeficiency, can have a deleterious effect on a patient’s health and even lead to death. Hence, splenectomy should be avoided and spleen preservation during elective surgery has become a treatment goal. However, this cannot be achieved in every patient due to intraoperative technical difficulties or oncological reasons. Autogenic splenic implantation (ASI) is currently the only possible way to preserve splenic function when a splenectomy is necessary. Experience largely stems from trauma patients with a splenic rupture. Splenic immune function can be measured by the body’s clearing capacity of encapsulated bacteria. The aim of this study is to assess the splenic immune function after ASI was performed during minimally invasive (laparoscopic or robotic) distal pancreatectomy with splenectomy.MethodsThis is the protocol for a multicentre, randomized, open-labelled trial. Thirty participants with benign or low-grade malignant lesions of the distal pancreas requiring minimally invasive distal pancreatectomy and splenectomy will be allocated to either additional intraoperative ASI (intervention) or no further intervention (control). An additional 15 patients who will undergo spleen-preserving distal pancreatectomy serve as the control group with normal splenic function. Six months postoperatively, after assumed restoration of splenic function, patients will be given a Salmonella typhi (Typhim Vi™) vaccine. The Salmonella typhi vaccine is a polysaccharide vaccine. The specific antibody titres immediately before and 4 to 6 weeks after vaccination will be measured. The ratio between pre- and post-vaccination antibody count is the primary outcome measure and secondary outcome measures include intraoperative details, length of hospital stay, 30-day mortality and morbidity.DiscussionThis study will investigate the splenic immune function of patients who undergo ASI during minimally invasive distal pancreatectomy with splenectomy. The splenic immune function will be measured using the surrogate outcome of specific antibody titre after vaccination with a Salmonella typhi vaccine. The results will reveal details about splenic function after ASI and guide further treatment options for patients when a splenectomy cannot be avoided. It might eventually lead to a new standard of care making sometimes more demanding and time-consuming spleen-preserving procedures redundant.Trial registrationInternational Standard Randomized Controlled Trials Number (ISRCTN) ISRCTN10171587. Prospectively registered on 18 February 2019.

Qualitative and quantitative imaging features of solid pancreas tumours in portal venous phase CT: are they useful in determining tumour type and grade?

Solid pancreatic lesions might have overlapping findings in portal venous phase computed tomography (CT). In this study, we aimed to investigate the quantitative and qualitative imaging features of solid pancreas lesions based on subtype and grade. The study group consisted of 159 patients with solid pancreatic tumours detected after exclusion criteria. According to the pathology results, the patients were divided into 3 groups as PDAC (pancreatic ductal adenocarcinoma, n = 137), PNET (pancreatic neuroendocrine tumour, n = 15), and SC (sarcomatoid carcinoma, n = 7). PDAC and PNET lesions were evaluated in 3 subgroups according to grade. There was no difference between the groups in terms of age, gender, tumour localisation, and internal structure (p = 0.23, p = 0.81, p = 0.19, and p = 0.94, respectively). Qualitative features significantly differed in terms of tumour margin feature, visual tumour density, presence of cystic component, and presence of necrosis (p = 0.01, p = 0.0001, p = 0.002, and p = 0.004, respectively). Tumour size, Tmden, Tmden/VPden, and Tmden/PanPden showed differences between groups (p = 0.0001, p = 0.002, p = 0.0001, p = 0.0001, respectively). The presence of cystic density in PDAC patients differed according to grade (p = 0.01). While ill-defined irregular margins, hypodense visual tumour density, no cystic component, low value of Tmden, and low ratios of Tmden/VPden and Tmden/PanPden indicate PDAC, regular margins, iso-or hyperdense visual tumour density, cystic component, high value of Tmden, and high ratios of Tmden/VPden and Tmden/PanPden indicate PNET. SC can be differentiated from them by containing necrosis and reaching larger sizes. The presence of a cystic component in PDAC patients indicates high grade.

Rare cystic lesion of pancreas : A case report

Hydatid disease also known as Hydatidosis or echinococcosis, the cause of which is the larval stage of Echinococcus granulosus. Pancreatic hydatidosis is very rare, with an incidence ranging from 0.14 to 2%. In this report we present a case of 51 years old female patient admitted in our hospital with a cystic lesion in the body of pancreas. Pre-operative computed tomography findings were suggestive of mucinous cystademona for which radical antegrade modular pancreatosplenectomy procedure was done.

Fine Needle Aspiration and Core Biopsy of Liver Mass as First Time Diagnosis of Sarcomatoid Anaplastic Thyroid Carcinoma, A Rare Malignancy Presenting at an Unexpected Body Site

Abstract Introduction/Objective Anaplastic thyroid carcinoma (ATC) is a fatal malignancy. We report an unusual case of a patient with ATC whose chief complaint and clinical history were listed as “jaundice and liver mass” without mention of disease in the neck. Methods/Case Report A 66-year-old female presented to the emergency department with worsening “yellow-green skin discoloration” for a few weeks. She also reported worsening dyspnea and recent dysphagia with solid foods, fatigue, abdominal pain and recent hemoptysis. Physical examination revealed conjunctival icterus, jaundice, a tender neck mass, right upper chest wall tenderness and palpable lymphadenopathy in the lower neck. Assessment notes indicated inability to carry out self-care and being bedridden, even though she reported having been active, swimming and cycling, up to one month before her presentation. Computed tomography studies confirmed findings compatible with widespread malignancy with mass lesions in her liver, lungs, adrenals, kidneys, neck, pancreas, gallbladder, and brain. Mild anemia, hemoglobin 10.5g/dL, mild leukocytosis, leukocytes 17,000/mm3, were confirmed. Bilirubin was 15µmol/L, and hepatic enzymes were elevated. An ultrasound-guided liver biopsy was performed and evaluated for cytologic features, histologic features and pattern of immunoreactivity. The combined cytomorphologic and histologic features were those of a pleomorphic sarcomatoid high-grade malignancy with variably spindled to epithelioid morphology and associated necrosis. Immunohistochemical studies performed on sections from the accompanying core biopsy confirmed the malignant cells to be positive with CK-AE1/AE3, CK 7, TTF-1, GATA3, PAX8, SATB2, and BRAF V600E. The malignant cells were nonreactive with CK 20, thyroglobulin, calcitonin, napsin, CDX2, PCEA, and ER. The combined clinical setting, imaging findings, cytomorphology, histomorphology and ancillary testing results together allowed for a specific diagnosis of metastatic anaplastic thyroid carcinoma. The patient was referred for palliative care services and died within a few days of diagnosis. Results (if a Case Study enter NA) NA Conclusion Metastatic disease from a sarcomatoid ATC, as diagnosed in this case, is an important differential diagnosis to keep in mind when an elderly patient presents with multisite metastases from an undefined primary source. Clinical, radiological and laboratory correlations are of paramount importance in correlating with cytomorphology/histomorphology and in helping to determine the best panel of IHC studies to consider.

Focal congenital hyperinsulinism

In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.

MODERN METHODS OF DIAGNOSIS AND TREATMENT OF ACUTE PANCREATITIS

We used modern diagnostic methods of instrumental investigations. All patients in this work was divided to groups depended on estimating patient statement with APACHE II and RANSON scale. Instead at this, we estimated multislice computed tomography sings depended on Balthazar scale. This scale helped us to purpose existing and spreading of the lesion in pancreas, prognoses course of the disease after diagnosing disease. We entered new diagnostic and treatment algorithms, which helps to chose right surgical methods of treatment of acute pancreatitis in different stages of disease. After using this tactics in patients with difficult forms of acute pancreatitis (total ball 3-9 on integral scale RANSON and 9-20 on APACHE II scale) results was: mortality 25.9%, which conforms to low limit prognosing mor-tality in this group.

Risk Factors and Interpretation of Inconclusive Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of Solid Pancreatic Lesions.

The inconclusive cytological findings of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) remain a major clinical challenge and often lead to treatment delays. Patients who had undergone EUS-FNA sampling for solid pancreas lesions between 2014 and 2021 were retrospectively enrolled. The "atypical" and "non-diagnostic" categories of the Papanicolaou Society of Cytopathology System were considered inconclusive and the "negative for malignancy" category of malignancy was suspected clinically. We determined the frequency and predictors of inconclusive cytological finding. A total of 473 first EUS-FNA samples were included, of which 108 cases (22.83%) were inconclusive. Significant increases in the odds of inconclusive cytological findings were observed for lesions with a benign final diagnosis (OR 11.20; 95% CI 6.56-19.54, p < 0.001) as well as with the use of 25 G FNA needles (OR 2.12; 95% CI 1.09-4.01, p = 0.023) compared to 22 G needles. Furthermore, the use of a single EUS-FNA technique compared to the combined use of slow-pull and standard suction techniques (OR 1.70; 95% CI 1.06-2.70, p = 0.027) and less than three punctures per procedure led to an elevation in the risk of inconclusive cytology (OR 2.49; 95% CI 1.49-4.14, p < 0.001). Risk reduction in inconclusive cytology findings was observed in lesions between 2-4 cm (OR 0.40; 95% CI 0.23-0.68, p = 0.001) and >4 cm (OR 0.16; 95% CI 0.08-0.31, p < 0.001) compared to lesions ≤2 cm. The more than two punctures per EUS-FNA sampling with larger-diameter needle (19 G or 22 G) using the slow-pull and standard suction techniques in combination may decrease the probability of inconclusive cytological findings.

Prospects of differential diagnosis of focal lesion of pancreas by the microRNA assessment

Purpose of the study. Identification of potential miRNA markers in material of focal pancreatic lesions.Materials and methods. Samples of focal pancreatic lesions after histological evaluation were enrolled in the study including chronic pancreatitis (ChP) (n = 23), low-grade pancreatic intraepithelial neoplasia /PanIN‑1/2 (n = 19), high-grade pancreatic intraepithelial neoplasia /PanIN‑3 (n = 8), and invasive pancreatic ductal adenocarcinoma PDAC (n = 26). Workflow of research included the profiling of cancer-associated miRNA in pooled samples, the selection of potential marker miRNAs, the assessment of selected miRNAs expression in total collection of specimens, the identification of differentially expressed miRNAs, and the approbation of new algorithm of data interpretation via ratio of “reciprocal miRNA pair”. Consequent reactions of revers transcription and quantitative teal-time PCR were used.Results. The expression levels of miR‑216a and miR‑217 were decreased in the following order: PanIN‑1/2 &gt; PanIN‑3 &gt; PDAC. Moreover, miR‑375 was up-regulated while miR‑143 was down-regulated in the PDAC. Differential diagnostics of PDAC versus focal chronic pancreatitis might be performed with high accuracy (AUC &gt; 0.95) by assessment panel of four molecules: miR‑216a, miR‑217, miR‑1246 and Let‑7a.Conclusion. The assessment of microRNAs in pancreatic lesions is a promising approach for the differential diagnosis of PDAC, but this technology requires further validation with an increase in the number of samples.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer

Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Pancreatic Mucinous Cystic Neoplasm with Associated Invasive Carcinoma: A Case Report and Literature Review

Background. Pancreatic mucinous cystic neoplasm (PMCN) with associated invasive carcinoma is a rare entity. According to the World Health Organisation (WHO) 2010, PMCN with associated invasive carcinoma is referred to the malignant lesions of the pancreatic epithelial tumour. Case report. A 52-year-old female patient presented with pain in the umbilical and epigastric regions for 5 months and noticed a solid visible tumour on the left side of the abdomen 3 months ago when she lied down. The level of the CA125 was 47.64 U/ml (normal value &lt;35 U/ml). Abdominal and pelvic magnetic resonance imaging (MRI) showed a cystic multiseptal mass in the left iliac region, defined as a left ovary tumour, while Computed tomography scan revealed a cystic tumour of the pancreatic tail. The patient underwent a resection of the pancreatic tail with a 20 cm cystic solid tumour, splenectomy and left hemicolectomy. Histopathology report confirmed mucinous cystic neoplasm of the pancreatic tail with associated invasive carcinoma (combined badly differentiated (G3) ductal (40%) and undifferentiated (G4) anaplastic (60%) carcinoma) pT1bN0. Postoperative course complicated with wound infection. The patient was discharged on postoperative day 10. The patient is still alive 2 years on follow-up. Conclusions. PMCN with associated invasive carcinomas are rare lesions of pancreas with relatively benign course. This malignant pancreatic tumour displays morphologies as pleomorphic epithelial cells and relatively mononuclear spindle cells, and not always tends to have underlying ovarian type stroma. The comprehensive histopathological examination of the tumour is necessary in order to cure most MCN patients with minimally invasive types.

Early experience with robotic central pancreatectomy with patient-reported outcomes and comparison with open central pancreatectomy.

Robotic central pancreatectomy (CP) has emerged in recent years as a noninferior approach to open CP and may offer improved patient-reported outcomes and reduction in incisional hernias. All patients who underwent open and robotic CP between (2013 and 2022) were selected, and perioperative outcomes were analyzed. Patients who underwent robotic CP were interviewed over the phone to assess patient-reported postoperative outcomes. A total of 18 CP operations (56%-open vs. 44%-robotic) were identified. The overall median age was 67 years (interquartile range: 60-72), and 50% (n = 9) of patients were female. Median length of surgery was statistically longer for robotic CP(411 vs. 138 min,p = 0.002); all other intraoperative variables were similar. Postoperatively, a similar number of patients in the open and robotic cohorts developed clinically significant postoperative pancreatic fistulas (37.5% vs. 30%,p = 1) and major complications (37.5% vs. 20%,p = 0.60), respectively. No patients in the robotic cohort developed an incisional hernia, compared to 40% (n = 4) in open (p = 0.08). All patients returned to a baseline level of activity and reported a high quality of life. With the exception of longer operative times, robotic CP is a noninferior, definitive resection technique for select lesions of the middle pancreas. Additionally, the robotic approach may result in a reduction in incisional hernia development.

Do Biliary Stents Affect EUS-Guided Tissue Acquisition (EUS-TA) in Solid Pancreatic Lesions Determining Biliary Obstruction? A Literature Review with Meta-Analysis.

There is a paucity of evidence regarding whether biliary stents influence endoscopic ultrasound-guided tissue acquisition using either fine-needle biopsy (EUS-FNB) or fine-needle aspiration (EUS-FNA), among patients with head of pancreas (HOP) lesions. We aimed at assessing the diagnostic accuracy of endoscopic ultrasound-guided tissue sampling in patients with or without bile duct stents. A total of seven studies with 2458 patients were included. The main aim was to assess overall pooled diagnostic accuracy. A pairwise meta-analysis was performed using a random effects model. Outcomes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). We found that pooled accuracy was 85.4% (CI 78.8-91.9) and 88.1% (CI 83.3-92.9) in patients with and without stents, respectively. There was no statistically significant difference between the two (OR 0.74; p = 0.07). Furthermore, patients with metal stents demonstrated a significant difference (OR 0.54, 0.17-0.97; p = 0.05), which was not seen with plastic stents. EUS-FNB showed poorer diagnostic accuracy with concurrent biliary stenting (OR 0.64, 0.43-0.95; p = 0.03); however, the same was not observed with EUS-FNA. Compared to plastic stents, metal biliary stenting further impacted the diagnostic accuracy of EUS-guided tissue acquisition for pancreatic head lesions. There was no difference in the rate of procedure-related adverse events between the stent and no-stent groups.

Hypoglycemic and hypolipidemic effect of pentaamino acid fullerene C60 derivative in rats with metabolic disorder.

Pentaamino acid fullerene C60 derivative is a promising nanomaterial, which exhibited antihyperglycemic activity in high-fat diet and streptozotocin-induced diabetic rats. This study investigates the effect of pentaaminoacid C60 derivative (PFD) in rats with metabolic disorders. Rats were assigned to 3 groups (of 10 rats each) as follows: Group 1 (normal control), group 2 included the protamine-sulfate-treated rats (the untreated group of animals with the model metabolic disorder); group 3 (Protamine sulfate + PFD) included the protamine-sulfate-treated model rats that received an intraperitoneal injection of PFD. Metabolic disorder in rats was initiated by protamine sulfate (PS) administration. The PS + PFD group was injected intraperitoneally with PFD solution (3mg/kg). Protamine sulfate induces biochemical changes (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) in the blood and morphological lesions in rat liver and pancreas. The potassium salt of fullerenylpenta-N-dihydroxytyrosine in protamine sulfate-induced rats normalized blood glucose level and the serum lipid profile and improved hepatic function markers. Treatment with PFD restored pancreas islets and liver structure of protamine sulfate-induced rats compared to the untreated group. PFD is a promising compound for further study as a drug against metabolic disorders.