Image-guided percutaneous microwave ablation for unresectable pancreatic cancers: A multicenter retrospective study.

OBJECTIVE: This study aims to assess the feasibility, effectiveness, and safety of image-guided percutaneous microwave ablation (PMWA) for unresectable pancreatic cancer. METHODS: In this retrospective study, 72 patients from four hospitals were enrolled between November 2009 and October 2022. Descriptive statistics were employed to describe the patients' characteristics and prognostic factors. The primary endpoint compassed the complete ablation rate (CAR), incidence of complications and the pain relief rate (PRR). RESULTS: The median age of the 72 patients was 61 (interquartile range (IQR) 52.5-67.0) years, with 62.5 % (45/72) being male. 26 cases received computed tomography (CT) guidance; 46 cases received ultrasound guidance. A total of 74 tumors were identified (2 in 2 patients), with 56.8 % (42/74) at the body and tail, and the rest at the head and neck. Overall, 73 ablation sessions were carried out, achieving a technical success rate (TSR) of 100 %. The CAR was 40.5 % (30/74). The median follow-up time was 4.6 (1-43.4) months. 50 % (36/72) of patients had died with a median overall survival (OS) of 5.6 (1-27) months. Regarding complications, 18.1 % (13/72) of cases were classified as grade I and II, and 9.8 % (7/72) as grade IIIa. Before surgery, 33 patients experienced pain symptoms, and the postoperative PRR was 96.7 % (32/33). The average pain score decreased from 6.3 (4-10) before surgery to 2.0 (0-8) after ablation (P<0.001). CONCLUSIONS: Image-guided PMWA for unresectable pancreatic cancer is safe and feasible, effectively relieving cancer pain and improving patients' the quality of life.

Lepidic Pulmonary Metastasis from Pancreatic Carcinoma Mimicking Organizing Pneumonia, Diagnosed by a Transbronchial Cryobiopsy.

A 78-year-old man with a history of pancreatic carcinoma underwent chest computed tomography (CT), which revealed a slowly enlarging consolidation in the right lower lobe. Forceps and percutaneous CT-guided lung biopsies showed no evidence of malignancy; therefore, organizing pneumonia was suspected. However, the patient's serum carbohydrate antigen 19-9 levels increased monthly, raising concerns about malignant lesions. A transbronchial cryobiopsy (TBCB) was performed to confirm the diagnosis of pulmonary metastasis of the pancreatic carcinoma. Pulmonary metastasis is an important differential diagnosis when chest CT shows consolidation, mimicking organized pneumonia. In addition, a TBCB can be a useful diagnostic tool for detecting lepidic growth patterns.

Gastrointestinal and intraperitoneal bleeding due to multiple pseudoaneurysms postpartial pancreatectomy: A case report and literature review.

Postoperative pancreatic fistula, a significant complication following pancreaticoduodenectomy, can lead to the development of pseudoaneurysms, which in turn can result in hemorrhagic and septic complications. Here, we present the case of a 67-year-old male patient diagnosed with pancreatic head carcinoma who underwent partial pancreatectomy. Ten days postsurgery, the patient experienced hemorrhagic shock due to intraperitoneal bleeding. Emergency exploratory laparotomy and implantation of a stent in the common hepatic artery successfully stopped the bleeding. However, the patient later developed gastrointestinal bleeding, and no apparent source was detected during endoscopic examination. Two complex transcatheter arterial embolization procedures were performed, successfully stopping the bleeding. It is crucial to consider pseudoaneurysm in cases of suspected biliary and pancreatic leakage. This case also underscores the importance of a thorough vascular assessment prior to placing a coated stent, to prevent postoperative obstruction of catheter access to the responsible vessel. Additionally, embolization via the external path of the stent proved feasible.

Intra-ampullary and Periampullary Carcinoma: Clinicopathological Comparison and Survival Outcomes.

Introduction The ampulla of Vater is a structure in the duodenal wall in which the biliary and pancreatic ducts open. Malignant epithelial tumors arising at this site are commonly referred to as ampullary adenocarcinomas. In this study, we compared the clinicopathological features of intra-ampullary and periampullary carcinomas, including survival outcomes. Methods This retrospective cross-sectional study was conducted at the Department of Pathology, Liaquat National Hospital. All radiologically suspected cases or biopsy-proven (endoscopic biopsy) cases of intra-ampullary/periampullary carcinoma were included in the study. All patients underwent surgical resection (Whipple's procedure/pancreatoduodenectomy). The classification of intra-ampullary and periampullary carcinomas was performed according to the College of American Pathologists (CAP) guidelines. Results Among the 188 case studies, most (61.7%, n = 116) were males, with a median age of 55 years. Most tumors were of the pancreatobiliary subtype (57.4%, n = 108). Similarly, intra-ampullary carcinoma was more common than periampullary carcinoma (61.7% vs. 38.3%). Intra-ampullary carcinoma showed a higher extent of involvement of adjacent structures, a higher frequency of perineural invasion, and a higher nodal stage than periampullary carcinoma. Similarly, the median disease-specific survival of intra-ampullary carcinoma was significantly lower (46 months) than that of periampullary carcinoma (53.5 months). Conclusion We found a higher incidence of intra-ampullary carcinoma in our study. In addition, intra-ampullary carcinoma had a worse survival rate and was associated with poorer pathological parameters, such as perineural invasion and higher nodal and tumor stages than periampullary carcinoma.

Gut microbio-me and pancreatic cancer.

BACKGROUND: The incidence of pancreatic cancer (pancreatic ductal adenocarcinoma - PDAC) is increasing, especially in developed countries. In 2021, 496,000 new PDAC cases were dia-gnosed worldwide. In the Czech Republic, the incidence is one of the highest in the world, with 2,332 new PDAC patients dia-gnosed in 2018. Due to the absence of symptoms in the early stages, approximately 50% of patients are initially dia-gnosed with distant metastases. Mortality is slightly lower than the incidence count and, despite significant advances in cancer research, PDAC remains a fatal dia-gnosis. However, microbio-me seems to be an interesting approach, and not only in PDAC patients. Microbio-me is defined as the set of all microorganisms (microbio-ta, i.e. bacteria, fungi, viruses, archaea, and protozoa) and their genome in a certain environment. In a physiological setting, the gut microbio-me is in symbio-sis with the host organism, maintaining the balance of metabolism, mucosal immunomodulation and regulating the digestion process. When dysregulation of the number or function of intestinal microorganisms occurs, dysbio-sis is developed. It may lead to metabolic and cardiovascular diseases, nervous system disorders, induction of intestinal inflammation, or carcinogenesis. Microbio-ta can induce carcinogenesis in multiple ways, such as by activating an inflammatory response, reducing the immune system's ability to eliminate damaged cells, and deregulation of the host genome by microbial metabolites. This deregulation may lead to an activation of pro-apoptotic and pro-proliferative proteins. To date, research shows that the gut or oral microbio-me may be involved in the development of PDAC. One of the most studied bacteria is Porphyromonas gingivalis. Other bacteria, such as Fusobacteria, Enterobacter, Klebsiella, Prevotella, and Rothia, have also been shown to play a role in PDAC. PURPOSE: The aim of this review article is to point out one of the possible mechanisms of cancerogenesis in PDAC patients and its therapeutic influence to reduce the incidence and improve the prognosis of this aggressive disease.

Head-to-head comparison of treatment sequences in advanced pancreatic cancer-Real-world data from the prospective German TPK clinical cohort study.

There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess real-world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab-paclitaxel (GEMNAB; n = 938) as palliative first-line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health-related quality of life (HRQoL) between three common first- to second-line treatment sequences, adjusting for time-varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5-fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5-fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor-risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5-fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%-confidence intervals. The estimated real-world effectiveness of the three treatment sequences evaluated were largely comparable. Poor-risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient-reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.

Expression of the laminin genes family and its relationship to prognosis in pancreatic carcinoma.

BACKGROUND AND STUDY AIMS: Laminin is an extracellular matrix molecule that is the major component of the basement membrane and plays a key role in regulating various processes. However, the association between the laminin gene family and the prognosis of pancreatic carcinoma has not been systematically investigated. PATIENTS AND METHODS: The role of the laminin gene family in pancreatic cancer was evaluated using data from the TCGA database. The effects of different expressions of members of the laminin gene family on pancreatic cancer survival were compared, and their primary cellular roles were examined. The effects of different expressions of positive family genes on proliferation, metastasis, and invasion, as well as EMT and ferroptosis in pancreatic cancer, were also examined. RESULTS: Based on univariate and multifactorial analysis of pancreatic cancer patients, LAMA3 was identified as an independent prognostic factor for overall survival in pancreatic cancer. LAMA3 was found to be enriched in the actin cytoskeleton, P53 signaling pathway, adhesion molecule junctions, pentose phosphate pathway, and regulatory differences in the cell cycle and focal adhesion. Additionally, high expression of LAMA3 was found to promote cancer proliferation, invasion, and metastasis, facilitate the EMT process, and inhibit ferroptosis. CONCLUSIONS: Our results identified LAMA3 was associated with the prognosis of patients with pancreatic cancer and may serve as a prognostic biomarker for pancreatic cancer.

K-ras mutation detected by peptide nucleic acid-clamping polymerase chain reaction, Ki-67, S100P, and SMAD4 expression can improve the diagnostic accuracy of inconclusive pancreatic EUS-FNB specimens.

OBJECTIVES: We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and K-ras mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases. METHODS: Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for K-ras mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed. RESULTS: K-ras mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases. CONCLUSIONS: K-ras mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose.

Small protein blockers of human IL-6 receptor alpha inhibit proliferation and migration of cancer cells.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that controls the immune response, and its role has been described in the development of autoimmune diseases. Signaling via its cognate IL-6 receptor (IL-6R) complex is critical in tumor progression and, therefore, IL-6R represents an important therapeutic target. METHODS: An albumin-binding domain-derived highly complex combinatorial library was used to select IL-6R alpha (IL-6Rα)-targeted small protein binders using ribosome display. Large-scale screening of bacterial lysates of individual clones was performed using ELISA, and their IL-6Rα blocking potential was verified by competition ELISA. The binding of proteins to cells was monitored by flow cytometry and confocal microscopy on HEK293T-transfected cells, and inhibition of signaling function was examined using HEK-Blue IL-6 reporter cells. Protein binding kinetics to living cells was measured by LigandTracer, cell proliferation and toxicity by iCELLigence and Incucyte, cell migration by the scratch wound healing assay, and prediction of binding poses using molecular modeling by docking. RESULTS: We demonstrated a collection of protein variants called NEF ligands, selected from an albumin-binding domain scaffold-derived combinatorial library, and showed their binding specificity to human IL-6Rα and antagonistic effect in HEK-Blue IL-6 reporter cells. The three most promising NEF108, NEF163, and NEF172 variants inhibited cell proliferation of malignant melanoma (G361 and A2058) and pancreatic (PaTu and MiaPaCa) cancer cells, and suppressed migration of malignant melanoma (A2058), pancreatic carcinoma (PaTu), and glioblastoma (GAMG) cells in vitro. The NEF binders also recognized maturation-induced IL-6Rα expression and interfered with IL-6-induced differentiation in primary human B cells. CONCLUSION: We report on the generation of small protein blockers of human IL-6Rα using directed evolution. NEF proteins represent a promising class of non-toxic anti-tumor agents with migrastatic potential.

Preliminary study on the ability of the machine learning models based on 18F-FDG PET/CT to differentiate between mass-forming pancreatic lymphoma and pancreatic carcinoma.

PURPOSE: The objective of this study was to preliminarily assess the ability of metabolic parameters and radiomics derived from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to distinguish mass-forming pancreatic lymphoma from pancreatic carcinoma using machine learning. METHODS: A total of 88 lesions from 86 patients diagnosed as mass-forming pancreatic lymphoma or pancreatic carcinoma were included and randomly divided into a training set and a validation set at a 4-to-1 ratio. The segmentation of regions of interest was performed using ITK-SNAP software, PET metabolic parameters and radiomics features were extracted using 3Dslicer and PYTHON. Following the selection of optimal metabolic parameters and radiomics features, Logistic regression (LR), support vector machine (SVM), and random forest (RF) models were constructed for PET metabolic parameters, CT radiomics, PET radiomics, and PET/CT radiomics. Model performance was assessed in terms of area under the curve (AUC), accuracy, sensitivity, and specificity in both the training and validation sets. RESULTS: Strong discriminative ability observed in all models, with AUC values ranging from 0.727 to 0.978. The highest performance exhibited by the combined PET and CT radiomics features. AUC values for PET/CT radiomics models in the training set were LR 0.994, SVM 0.994, RF 0.989. In the validation set, AUC values were LR 0.909, SVM 0.883, RF 0.844. CONCLUSION: Machine learning models utilizing the metabolic parameters and radiomics of 18F-FDG PET/CT show promise in distinguishing between pancreatic carcinoma and mass-forming pancreatic lymphoma. Further validation on a larger cohort is necessary before practical implementation in clinical settings.