Biliary Carcinoma Research Articles

Lobar and Segmental Atrophy of the Liver: Differential Diagnoses and Treatments

Segmental or lobar liver atrophy is a common but not well-understood clinical condition. Hepatic atrophy can be classified into hepatic atrophy secondary to other pathologies and primary segmental hepatic atrophy, which is a benign intrahepatic lesion (pseudotumor) not associated with any other pathology. The pathophysiological mechanisms underlying atrophy can be divided into three main situations: obstruction of biliary outflow, obstruction of the systemic venous outflow, and obstruction of incoming portal venous flow. For what may concern secondary hepatic atrophy, there are many pathologies that could underlie this condition, ranging from benign to intrahepatic malignancies, with particular reference to particularly hepatocellular carcinoma and biliary duct carcinoma. An accurate and prompt differential diagnosis between the various forms and causes of atrophy is important for early identification and adequate treatment of underlying pathologies. A comprehensive review of the literature on the etiology and the radiological and histological characteristics of different types of hepatic atrophy is currently unavailable. Therefore, the aim of this review is to summarize the primary and secondary causes of segmental or lobar liver atrophy (excluding forms involving the entire liver parenchyma) and to provide practical tools for clinical and radiological differential diagnosis.

Computed Tomography Evaluation of Gall Bladder Mass with Histopathological Correlation

Background: In extrahepatic biliary carcinoma patients, unresectable disease is frequently discovered during exploration despite thorough preoperative assessment, leading to unnecessary laparotomy. Gallbladder carcinoma ranks fifth among gastrointestinal malignancies, following colorectal, pancreatic, gastric, and esophageal carcinomas. Aim of the study: The aim of the study was to establish the diagnostic usefulness of computed tomography (CT) in the diagnosis of gallbladder mass. Methods: This case-control study was conducted at the Department of Radiology and Imaging, Rajshahi Medical College Hospital, Rajshahi, Bangladesh from March 2018 to August 2018. The study included 65 patients diagnosed with a gallbladder mass, selected through purposive sampling. SPSS version 23.0 was utilized for data analysis. Results: CT scans accurately predicted various features of gallbladder mass, showing high sensitivity, specificity, and accuracy, with positive and negative predictive values of ≥95% for adenocarcinoma, squamous carcinoma, cholecystitis, metastases, GB polyp, and adenoma. Chronic cholecystitis sensitivity was over 83%. Overall, CT diagnosis performed at least 88.9% across all features. The histopathological assessment also detected nearly similar features of gallbladder mass. Conclusion: Computed tomography (CT) serves as a valuable diagnostic tool for distinguishing gallbladder neoplasms preoperatively. It is worth noting that CT scans aid in the rational management approach for patients with gallbladder neoplasms.

5-Hydroxymethylcytosine (5-hmC) loss is a marker of malignancy in biliary neoplasms.

Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies. We evaluated 93 cases-20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas-for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls. Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P > .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases. Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics.

Early and late outcomes of congenital biliary dilatation in pediatric patients.

This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy.

Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

Does Congenital Biliary Dilatation Todani Type II (Diverticular Type) Really Exist?

Aim of the studyThe aim of the study is to clarify the clinicopathological and biliary morphological characteristics in reported cases of diverticular congenital biliary dilatation (CBD). MethodUsing PubMed and the Japan Medical Abstracts Society, articles on possible diverticular CBD were extracted and the clinical pictures examined. We also sought evidence for definitions of diverticular CBD and the associated condition of pancreaticobiliary maljunction (PBM) using the original articles by Alonso-Lej and Todani. The characteristic biliary morphologies of cases with images were also investigated. ResultsAnalyses of 211 possible cases superficially demonstrated multiple diverticula in 12 (12%) and single diverticulum in 89 (88%), with diverticula located in the upper (n = 38, 38%), middle (n = 32, 32%), or lower (n = 26, 26%) biliary tract in and presence of intra-diverticular stones, PBM, and biliary carcinoma in 23% (n = 18), 39% (n = 25), and 11% (n = 14), respectively. However, evidence defining diverticular CBD or justifying the lack of associated PBM was not demonstrated even in the original articles. Scrutiny of the biliary anatomy in 59 cases with images showed incorrect inclusions of types I or IV-A with an irregular biliary duct wall or dilated cystic duct, periampullary choledochal diverticula, or even solitary biliary cysts. Authentic diverticular CBD, representing the diverticulum connected to the middle of the common bile duct via a thin, patent stalk was seen in only 6 cases. ConclusionReal diverticular CBD appears extremely rare. The lack of an objective definition allows wide interpretations of clinical pictures, creating inconsistencies in the diagnosis and treatment of CBD and raising questions regarding the utility of conventional classifications. Level of evidenceLevel III.

Perineural Invasion and Spread in Common Abdominopelvic Diseases: Imaging Diagnosis and Clinical Significance.

Malignancies and other diseases may spread by multiple pathways, including direct extension, hematogenous spread, or via lymphatic vessels. A less-well-understood route is the peripheral nervous system, which is known as perineural spread (PNS). In addition to accounting for pain and other neurologic symptoms, PNS affects both disease prognosis and management. Although PNS is commonly discussed in relation to head and neck tumors, there is emerging data regarding PNS in abdominopelvic malignancies and other conditions such as endometriosis. Due to improved contrast and spatial resolution, perineural invasion, a finding heretofore diagnosed only at pathologic examination, can be detected at CT, MRI, and PET/CT. PNS most commonly manifests as abnormal soft-tissue attenuation extending along neural structures, and diagnosis of it is aided by optimizing imaging parameters, understanding pertinent anatomy, and becoming familiar with the typical neural pathways of spread that largely depend on the disease type and location. In the abdomen, the celiac plexus is a central structure that innervates the major abdominal organs and is the principal route of PNS in patients with pancreatic and biliary carcinomas. In the pelvis, the lumbosacral plexus and inferior hypogastric plexus are the central structures and principal routes of PNS in patients with pelvic malignancies. Although the imaging findings of PNS may be subtle, a radiologic diagnosis can have a substantial effect on patient care. Knowledge of anatomy and known routes of PNS and optimizing imaging parameters is of utmost importance in providing key information for prognosis and treatment planning. © RSNA, 2023 Supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

COVID-19 induced remission of biliary and renal cell carcinomas.

e14598 Background: Clear cell renal carcinoma and cholangiocarcinoma are resistant to standard therapy. Complete remissions are rare. SARS-CoV-2 (COVID-19) boosts anti-viral immune responses but effects on cancers are unknown. Case reports of hematologic cancer remissions after COVID infection are emerging. Anti PD1/PD-L1 antibody therapy have prolonged remission in 20% of solid tumor patients. mRNA COVID-19 vaccines and COVID-19 active infections create anti-viral immune responses - increased IgG titers, SARS-CoV-2-specific antibodies, and boost T-cell response. Anti PD-1/PD-L1 antibodies immune responses, are presumed independent of the immune response to COVID vaccination/infection. Two previous case reports of hematologic remission were seen after COVID infection. (Hodgkins, multiple myeloma). There are no cases of solid cancer remission after COVID-19 exposure. Methods: Three patients with solid cancers and complete/near complete radiographic remissions after COVID-19 exposure. Two on low carbohydrate diets. History, dietary course and clinical outcomes are presented. Results: Case 1: 58 year old male diagnosed with stage IV clear cell renal carcinoma (lung nodules, mediastinal nodes). After 5 years he progressed on Sunitinib and began Nivolumab. His cancer stabilized but hypophysitis, diarrhea, severe jaw pain ended his treatment. After COVID-19 booster vaccine, he became anorexic, lost 50 lbs over 8 weeks (267 to 211 lb). Relapse was suspected but PET CT showed complete resolution of his lung nodules and adenopathy. Asymptomatic and in remission over 9 months post vaccine. Case 2: 51 year old male heavily pretreated stage 4 renal cell cancer, bone, liver, nodal metastases. On Nivolumab with stable disease but after COVID booster vaccine had high fever, fatigue, myalgia. PET CT scans later showed near complete resolution of his bony, hepatic and nodal metastatic sites. Case 3: 75 year old male with unresectable cholangiocarcinoma on second line Atezolizumab. COVID-19 infection was followed by complete radiographic remission. Conclusions: Effects of SARS-CoV-2 (COVID-19) on cancers remain unknown. Few case reports of cancer remissions after infections are emerging. These are two cases of renal cell cancers in complete remission after COVID-19 vaccination while on immunotherapy. Both followed low glycemic diets. Third case was a complete remission of biliary cancer after an acute COVID-19 infection. Proposed anti-cancer mechanisms - pathogen specific T cell action, anti-inflammatory effects against COVID-19 infection, cross-reactivity against tumor antigens, natural killer cell activation. COVID-19 proteins have oncolytic properties - HIV related B cell apoptosis and Coxsackievirus A21 oncolytic effects on myeloma and CD138+ plasma cells via intercellular adhesion molecule interaction. COVID-19’s effects plus the anti PD-1/PD-L1 antibodies immune response may be synergistic and merits further research.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare distinct subtype of precursor lesions of biliary carcinoma. IPNB is considered to originate from luminal biliary epithelial cells, typically displays mucin-hypersecretion or a papillary growth pattern, and results in cystic dilatation[1]. IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts, and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma. IPNBs have similar phenotypic changes in the occurrence and development of all subtypes, and the prognosis is significantly better than that of traditional (non-papillary) cholangiocarcinoma. To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment. Invasive IPNB, invasive intraductal papillary mucinous neoplasm of the pancreas (IPMN), and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Annual percentage changes (APCs) in the incidence and incidence-based (IB) mortality were calculated. We identified the independent predictors of overall survival (OS) and cancer-specific survival (CSS) in individuals with invasive IPNB. The incidence and IB mortality of invasive IPNB showed sustained decreases, with an APC of -4.5% (95%CI: -5.1% to -3.8%) and -3.3% (95%CI: -4.1% to -2.6%) (P < 0.001), respectively. Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma. Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma. A total of 1635 individuals with invasive IPNB were included in our prognosis analysis. The most common tumor sites were the pancreaticobiliary ampulla (47.9%) and perihilar tract (36.7%), but the mucin-related subtype of invasive IPNB was the main type, intrahepatically (approximately 90%). In the univariate and multivariate Cox regression analysis, age, tumor site, grade and stage, subtype, surgery, and chemotherapy were associated with OS and CSS (P < 0.05). Incidence and IB mortality of invasive IPNB trended steadily downward. The heterogeneity of IPNB comprises site and the tumor's mucin-producing status.

The Epithelial Sodium Channel-An Underestimated Drug Target.

Epithelial sodium channels (ENaC) are part of a complex network of interacting biochemical pathways and as such are involved in several disease states. Dependent on site and type of mutation, gain- or loss-of-function generated symptoms occur which span from asymptomatic to life-threatening disorders such as Liddle syndrome, cystic fibrosis or generalized pseudohypoaldosteronism type 1. Variants of ENaC which are implicated in disease assist further understanding of their molecular mechanisms in order to create models for specific pharmacological targeting. Identification and characterization of ENaC modifiers not only furthers our basic understanding of how these regulatory processes interact, but also enables discovery of new therapeutic targets for the disease conditions caused by ENaC dysfunction. Numerous test compounds have revealed encouraging results in vitro and in animal models but less in clinical settings. The EMA- and FDA-designated orphan drug solnatide is currently being tested in phase 2 clinical trials in the setting of acute respiratory distress syndrome, and the NOX1/ NOX4 inhibitor setanaxib is undergoing clinical phase 2 and 3 trials for therapy of primary biliary cholangitis, liver stiffness, and carcinoma. The established ENaC blocker amiloride is mainly used as an add-on drug in the therapy of resistant hypertension and is being studied in ongoing clinical phase 3 and 4 trials for special applications. This review focuses on discussing some recent developments in the search for novel therapeutic agents.

The Wnt signaling pathway in gastrointestinal cancers.

807 Background: Activation of the Wnt signaling pathway leads to increases in β-catenin levels, which subsequently increases transcription of various genes, including those involved in cell proliferation. Dysregulation of the Wnt signaling pathway has been observed in numerous gastrointestinal (GI) cancers. Here we examine Wnt pathway activation across all GI cancers by investigating alterations in certain genes of the Wnt pathway, which may identify patients eligible for clinical trials. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Alterations in genes that activate Wnt signaling and their frequency across all GI cancers was determined. Results: A total of 1928 patients assayed April 2018 to July 2022 were included. The Wnt signaling pathway was activated in 922 (47.8%) patients. Wnt pathway activation varied substantially across GI cancers, from 81.1% in colorectal cancer (CRC) to 3.4% in anal cancer. APC was the most commonly altered gene in CRC, small bowel and biliary carcinomas. CTNNB1 was predominant in liver (41.2%), MEN1 in neuroendocrine (14.6%), and RNF43 in gastric (9.4%) cancer. Of 921 patients with alterations in the Wnt pathway, 5.2% had a co-mutation in another Wnt pathway-related gene. RSPO2/3 fusions were found in 4 CRC, 1 stomach, 1 biliary, and 1 small bowel cancer and were mutually exclusive with other alterations in the Wnt pathway. Conclusions: Wnt signaling is activated in about half of all GI cancers, and APC alterations are the most frequently observed. Whole transcriptome profiling allowed us to identify RSPO2/3 fusions, which also contribute to activation of the Wnt pathway. Wnt activation appears to be a particularly important in CRC, with 81.1% of CRC having a Wnt pathway alteration. Our results highlight the therapeutic potential of targeting the abnormal Wnt/β-catenin signaling pathway in GI malignancies. [Table: see text]

Extrahepatic bile duct resection with pump placement for biliary large cell neuroendocrine carcinoma

Background: Primary large cell neuroendocrine carcinoma (LCNEC) of the extrahepatic bile ducts is extremely rare, with seven cases reported in the English literature. The infrequency in which LCNEC occurs poses significant diagnostic and therapeutic challenges.

A Case Report of Intraductal Papillary Neoplasm Associated with an Extrahepatic Bile Ducts

Choledochal cysts are congenital cystic dilations of the extrahepatic and/or intrahepatic bile ducts and are rare. Adults with choledochal cysts are at risk of developing biliary carcinoma. Our case is a 31-year-old female patient who presented with right upper quadrant pain. In magnetic resonance imaging/magnetic resonance cholangiopancreatography, there was a fusiform enlargement of the extrahepatic bile duct and cystic duct and it was evaluated as compatible with Type 1 choledochal cyst. Extrahepatic biliary tract excision-cholecystectomy-Roux En Y hepaticojejunostomy procedure was performed. The pathology result was intraductal papillary neoplasm (IPN). IPN is a rare entity in the biliary tract and because it is precancerous, early diagnosis and surgical excision are critical.

Particle Beam Therapy for Intrahepatic and Extrahepatic Biliary Duct Carcinoma: A Multi-Institutional Retrospective Data Analysis.

To examine the efficacy and toxicity of particle beam therapy (PT) for biliary duct carcinoma (BDC) and compare the outcomes between extrahepatic BDC (eBDC) and intrahepatic BDC (iBDC). We analyzed multi-institutional data from May 2009 to December 2019. The primary endpoint was overall survival (OS), and the secondary endpoints were local control (LC), progression-free survival (PFS) and toxicity. We included 150 patients with unresectable BDC treated with PT using a median prescribed dose of 70.2 GyRBE (range, 44-77 GyRBE) in 25 fractions (range, 10-38 fractions). With a median follow-up of 13.0 months, median survival time (MST) was 21 months, and 2-year OS was 44.8%. For eBDC and iBDC, the MSTs were 20 and 23 months, respectively. Two-year PFS and LC rates were 20.6% and 66.5%, respectively. Vascular invasion, prescribed dose and serum tumor marker level (carcinoembryonic antigen: CEA) were identified as poor prognostic factors for OS. A higher radiation dose EQD2 ≥ 67 Gy showed superior OS, with a hazard ratio of 0.341. The radiation dose of PT is an important predisposing factor for overall survival. The MST for patients with eBDC given a higher radiation dose was 25 months, compared to 15 months for those given the lower dose and 23 months for patients with iBDC (all iBDC given higher doses). iBDC and eBDC duct carcinomas showed equivalent outcomes with PT, especially when treated with a high radiation dose. In detailed analysis, baseline CEA level in iBDC, and radiation dose and GTV in eBDC were statistically significant predicators for OS. Acute and late toxicity grade ≥3 occurred in 2.2% and 2.7% of patients, respectively, including two late grade-5 toxicities. In conclusion, PT showed good efficacy for BDC, both eBDC and iBDC, with a low incidence of severe toxicity.

S1913 A Rare Case of Spindle Cell Carcinoma of the Hepatobiliary System

Introduction: Spindle cell also known as undifferentiated carcinomas of the pancreas (UCP) are rare anaplastic deviations of ductal adenocarcinomas of the pancreas. The general nature of these tumors is associated with destructive biological behavior and usually have a poor prognosis compared to most common variants of ductal adenocarcinoma. UCP include spindle cell carcinoma, sarcomatoid carcinoma and carcinosarcoma. In practice, it is hard to differentiate these subtypes since most of them possess a spindle element. UCPs are extremely rare tumors with a frequency of less than 2% of pancreatic exocrine tumors. Furthermore, UCP with focal osteochondroid differentiation are even rarer. Case Description/Methods: A 50-year-old man with past medical history of cardiovascular disease, hypertension, hepatitis C & external hemorrhoids presented with worsening abdominal pain, nausea, vomiting. CT was notable for evidence of a hepatobiliary mass. Gastroenterology was consulted and performed an EGD. Upon initial evaluation of the stomach into the antrum, a large, perforated ulcer was identified with omental tissue. Additionally, liver parenchyma was visualized along with severe LA Grade D Esophagitis throughout the entire esophagus. Interventional radiology was consulted and subsequently performed a biopsy of the mass in which the pathological findings were suggestive of Spindle cell carcinoma/carcinosarcoma. CT chest was ordered for staging and showed several nodules of unclear origin. Oncology was consulted and patient was initiated on chemotherapy (Carboplatin/Gemcitabine). Once on chemotherapy, the patient grew reluctant about receiving medical management. Palliative care was consulted. Considering advanced stage spindle cell hepatopancreatic biliary carcinoma leading to multiple complications including duodenal perforation, peritonitis, sepsis, encephalopathy leading to terminal delirium, patient's prognosis was deemed very poor with less than 6 months requiring hospice care. Patient was then transferred to inpatient hospice service (Figure). Discussion: The reported prognosis of each of the histologic subtypes of UCP have overall poor prognosis. Surgery is the first choice for a resectable undifferentiated carcinoma. In a previous study it was identified that average post-operative survival interval was 6 months and the longest living patient survived for 15 months.Figure 1.: H&E immunochemistry stain of liver biopsy.

S1817 Primary Squamous Cell Biliary Carcinoma With Liver Metastasis Is Rare but Malicious

S1817 Primary Squamous Cell Biliary Carcinoma With Liver Metastasis Is Rare but Malicious

Ex-vivo human pancreatic specimen evaluation by 7 Tesla MRI: a prospective radiological-pathological correlation study

To compare the characteristics detected by 7Tesla (7T) MR and the histological composition of ex-vivo specimens from lesions diagnosed at preoperative CT scan as Pancreatic Ductal Adenocarcinoma (PDAC). Ten pancreatic specimens were examined. The 7T imaging protocol included both morphologic and quantitative sequences; the latter was acquired by conventional methods and a novel multiparametric method, the magnetic resonance fingerprinting (MRF) sequence. Two radiologists reviewed the images to: (1) evaluate the quality of the morphological and quantitative sequences by assigning an "image consistency score" on a 4-point scale; (2) identify the lesion, recording its characteristics; (3) perform the quantitative analysis on "target lesion" and "non target tissue". Finally, the specimen was analysed by two pathologists. Seven out of 10 lesions were PDAC, 2/10 were biliary carcinomas, whereas one lesion was an ampullary adenocarcinoma. The quality of the morphological sequences was judged "excellent". The "image consistency score" for the conventional quantitative sequences and MRF were 2.8 ± 0.42 and 2.9 ± 0.57; the "overall MR examination score" was 3.5 ± 0.53. A statistical correlation was found between the relaxation time values of conventional and MRF T1-weighted sequences (p < 0.0001), as well as between conventional and MRF fat- and water-fraction maps (p < 0.05). The "target lesion" and "non target tissue" relaxation time values were statistically different according to conventional T1-, T2-weighted, and MRF T1-weighted sequences. Conventional T1-, T2-weighted sequences and MRF derived relaxometries may be useful in differentiating between tumour and non-target pancreatic tissue. Moreover, the MRF sequence can be used to obtain reliable relaxation time data.

Metzolimos metronomic cyclophosphamide (CP) and methotrexate (MTX) combined with zoledronic acid (ZA) and sirolimus (SIR) in patients with advanced solid tumor with bone metastasis and advanced pretreated osteosarcoma (OSS): A phase Ib study.

11526 Background: Advanced pretreated OSS has a very poor prognosis. Metronomic CP and MTX have shown little activity in pediatric cancers, including OSS. Preclinical data suggest that ZA could have a synergic effect when combined with mTOR inhibition in OSS. Methods: This is a prospective phase Ib study investigating the combination of SIR with CP, MTX and ZA trough a dose-escalation phase (3 + 3 design) in patients ≥ 18 years with bone metastatic solid tumors (part I) and an expansion cohort dedicated to patients ≥ 13 years with advanced pretreated OSS (part II). SIR was given at two dose levels (4 mg and 6 mg) continuously, in combination with CP 50 mg x 2 per day, 1 week on / 1 week off, MTX at 2.5 mg x 2 per day, on day 1 and day 4 every week, and ZA 4mg IV every 4 weeks. Primary endpoints were dose limiting toxicities (DLT), maximum tolerated dose and recommended phase II dose (RP2D) of SIR combined with CP, MTX and ZA for Part I, and 6-month non-progression rate (NPR) according to RECIST v1.1 for part II. Secondary endpoints included safety, 6-month objective response rate (ORR), one-year progression-free (PFS) and overall survivals (OS), and pharmacodynamics biomarker analyses. At least one non-progression at 6 months after centralized review of imaging was needed among 14 patients to consider activity of the combination. Results: From February 2015 to March 2021, 23 patients were included in the three participating centers. In part I, nine patients with breast (56%), prostate (33%) or biliary duct carcinoma (11%) were included. Median number of cycles was 2 (1-6). Two DLT were reported at dose level 2: one grade 3 neutropenia and one grade 3 anemia, therefore dose level 1 was the RP2D for part II. In part II, 14 OSS patients were included. Median age was 27 years (14 - 80). Median number of previous lines in the advanced disease was 1 (1-3). At the time of analysis, 11 patients had died. Reason for study discontinuation was progressive disease for 10 patients (72%), toxicity for two (14%) (one grade 2 platelet count decrease and one grade 5 unrelated lung infection), and investigator decision for two (14%) , including one for cryotherapy of a residual lesion after an excellent partial response. Overall, 64 adverse events related to study drugs were reported, of which 14 (22%) grade 3, and 2 grade 4 (3%). They were mainly asthenia, nausea, mucositis oral, anemia, lymphocyte and platelet count decrease. Median follow up was 27.5 months [95% CI : 12.8-27.5]. Two non-progressions at 6 months (14%) were observed, including a partial response (7%). One-year PFS was 21.4% [95%CI 5.2-44.8] and median OS was 12.8 months [95% CI : 2.8-20.4]. Conclusions: The combination of SIR at 4 mg daily with CP, MTX and ZA has an acceptable toxicity profile and reached the initial targeted efficacy rate in advanced pretreated OSS patients. Clinical trial information: NCT02517918.

Radiologische Aspekte der neuen deutschen S3-Leitlinie zum hepatozellulären Karzinom und biliären Karzinomen im internationalen Vergleich

The updated German S3 guideline "Diagnostics and therapy of hepatocellular carcinoma and biliary carcinomas" covers two tumor entities. The original guideline published in 2013 focusing only on the diagnosis and therapy of hepatocellular carcinoma (HCC) has been expanded to include intrahepatic cholangiocarcinoma. These guidelines were developed within the framework of the guideline program on oncology of the Scientific Medical Society e. V. (AWMF), the German Cancer Society (DKG) and German Cancer Aid Society (DKG) under the auspices of the German Society for Digestive and Metabolic Diseases (DGVS). In addition to updated recommendations regarding histopathology, radiological diagnostics and treatments, the main innovations of the revised guidelines on HCC include acomplete revision of the section on the systemic therapeutic approach in advanced stages of the disease. This article presents the significance of the current recommendations for diagnostic and interventional radiology in comparison to other national and international guidelines and should serve to improve the quality of patient care through more widespread dissemination.

Guideline-based thermal ablation of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is fifth most common cancer worldwide. The German S3guideline on the diagnosis and the treatment of hepatocellular and biliary carcinoma was recently revised. Determination of the current status of thermal ablation in HCC according to the German S3guideline. Based on the current guideline and aselective literature search, the current status on indication and application of thermal ablation in HCC was revisited. Radiofrequency ablation (RFA) and microwave ablation (MWA) provide similar survival when compared with surgery. Accordingly, RFA und MWA are considered first-line treatments for HCCs ≤ 3 cm in cirrhotic livers. For HCCs with diameters of 3-5 cm, acombination of transarterial chemoembolization and thermal ablation is recommended. The current S3guideline on diagnosis and treatment of HCC comprises relevant changes regarding thermal ablation in HCC. The overall role of interventional oncology procedures in the treatment of HCC was reinforced.