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BMC Medical Genomics May 2024Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the... (Review)
Review
BACKGROUND
Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations.
CASE PRESENTATION
A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5'UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient's history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified.
CONCLUSIONS
To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.
Topics: Humans; Tuberous Sclerosis; Female; Adult; Kidney Neoplasms; Carcinoma, Renal Cell; Tuberous Sclerosis Complex 2 Protein; Tuberous Sclerosis Complex 1 Protein; Mutation
PubMed: 38802873
DOI: 10.1186/s12920-024-01913-8 -
Pancreatology : Official Journal of the... May 2024Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different...
BACKGROUND
Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure.
METHODS
To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies.
CLINIC INFRASTRUCTURE
The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation.
RESULTS
A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance.
CONCLUSIONS
The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.
PubMed: 38796308
DOI: 10.1016/j.pan.2024.05.525 -
Gastrointestinal Endoscopy Clinics of... Jul 2024Pancreatic fluid collections (PFCs) are commonly encountered complications of acute and chronic pancreatitis. With the advancement of endoscopic ultrasound (EUS)... (Review)
Review
Pancreatic fluid collections (PFCs) are commonly encountered complications of acute and chronic pancreatitis. With the advancement of endoscopic ultrasound (EUS) techniques and devices, EUS-directed transmural drainage of symptomatic or infected PFCs has become the standard of care. Traditionally, plastic stents have been used for drainage, although lumen-apposing metal stents (LAMSs) are now favored by most endoscopists due to ease of use and reduced procedure time. While safety has been repeatedly demonstrated, follow-up care for these patients is critical as delayed adverse events of indwelling drains are known to occur.
Topics: Humans; Drainage; Endosonography; Stents; Pancreatitis; Pancreatic Pseudocyst
PubMed: 38796299
DOI: 10.1016/j.giec.2024.02.008 -
Gastrointestinal Endoscopy Clinics of... Jul 2024Endoscopic ultrasound (EUS) has rapidly evolved from a diagnostic to a therapeutic tool with applications for various pancreaticobiliary diseases. As part of this... (Review)
Review
Endoscopic ultrasound (EUS) has rapidly evolved from a diagnostic to a therapeutic tool with applications for various pancreaticobiliary diseases. As part of this evolution, EUS-guided chemoablation for neoplastic pancreatic cysts is developing as a minimally invasive treatment option for appropriately selected mucinous cysts, which can spare patients major resective surgery and may reduce progression to pancreatic cancer. Chemotherapeutic cyst ablation has demonstrated encouraging complete resolution rates, while an alcohol-free chemoablation protocol has demonstrated a significant decrease in adverse events without a compromise to complete ablation rates when compared with previous alcohol-based protocols. Most pancreatic cysts are small, low risk, and best managed by surveillance per accepted guidelines. Cysts with features suggestive of overt malignancy are best discussed by a multidisciplinary committee, and surgery is considered if appropriate. However, for patients in the middle ground with cysts that are structurally suitable for chemoablation, alcohol-free chemoablation has been shown to allow effective, safe, and durable results especially for those who are not ideal operative candidates. EUS-guided alcohol-free chemoablation is promising and continues to evolve; however, as a relatively novel treatment option it has areas of uncertainty that will require further investigation and development.
Topics: Humans; Pancreatic Cyst; Endosonography; Ablation Techniques; Pancreatic Neoplasms; Ultrasonography, Interventional
PubMed: 38796298
DOI: 10.1016/j.giec.2024.02.005 -
Gastrointestinal Endoscopy Clinics of... Jul 2024Management of symptomatic chronic pancreatitis (CP) has shifted its approach from surgical procedures to minimally invasive endoscopic procedures. Increased experience... (Review)
Review
Management of symptomatic chronic pancreatitis (CP) has shifted its approach from surgical procedures to minimally invasive endoscopic procedures. Increased experience and advanced technology have led to the use of endoscopic retrograde cholangiopancreatography (ERCP) as a therapeutic tool to provide pain relief and treat CP complications including pancreatic stones, strictures, and distal biliary strictures, pseudocysts, and pancreatic duct fistulas. In this article the authors will discuss the use of ERCP for the management of CP, its complications, recent advancements, and techniques from the most up to date literature available.
Topics: Humans; Pancreatitis, Chronic; Cholangiopancreatography, Endoscopic Retrograde; Stents; Constriction, Pathologic; Pancreatic Pseudocyst; Sphincterotomy, Endoscopic
PubMed: 38796292
DOI: 10.1016/j.giec.2024.02.004 -
Journal of Cystic Fibrosis : Official... May 2024Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve nutritional status and are of importance in achieving normal growth among younger children...
BACKGROUND
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve nutritional status and are of importance in achieving normal growth among younger children with CF. The study was designed to examine CFTR modulator-associated changes in nutrition status, including bile acids and fatty acids after lumacaftor/ivacaftor therapy for 24 weeks.
METHODS
Children 2 to 5.9 years were recruited from US and Canadian CF Centers. Eligible children were lumacaftor/ivacaftor naïve and approved to initiate therapy. Anthropometrics, diet, energy expenditure, nutrition biomarkers, pancreatic status, serum and fecal calprotectin, serum bile acids and plasma fatty acids were measured. Changes from baseline at 12 and 24 weeks were examined using mixed effects linear regression modeling.
RESULTS
Weight-for-age z-score (WAZ) increased at 12 (0.15 ± 0.1, p = 0.01) and 24 weeks (0.23 ± 0.1, p = 0.001) from baseline following modulator therapy. Head circumference-for-age (HCZ) increased at 12 weeks compared to baseline (0.22 ± 0.1, p = 0.03) and subscapular Z score increased from baseline at 24 weeks following therapy (0.33 ± 0.1, p = 0.02). There were no changes in energy expenditure. Serum total bile acids (6.7 ± 2.0, p = 0.001), chenodeoxycholic acid (CDCA) (2.4 ± 1.1, p = 0.001), and cholic acid (CA) (3.5 ± 0.8, p < 0.0001) increased at 24 weeks compared to baseline. Fecal calprotectin decreased at 12 and 24 weeks compared to baseline (-463 ± 310, p = 0.03 and 566 ± 347, p = 0.047). A number of plasma fatty acids changed over the course of 24 weeks of therapy. Noteably, alpha-linolenic acid (ALA) decreased at 12 and 24 weeks (-24 ± 10,p = 0.03 and -18 ± 10, p = 0.02, respectively).
CONCLUSIONS
Overall, young children experienced favorable changes in nutritional and growth, with the exception of plasma ALA status in the first 24 weeks of lumacaftor/ivacaftor therapy.
PubMed: 38789320
DOI: 10.1016/j.jcf.2024.05.005 -
Diagnostics (Basel, Switzerland) May 2024Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant... (Review)
Review
Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant transformation. The management of PCL involves complex decision-making, with postoperative surveillance being a key component for long-term outcomes, due to the potential for recurrence and postoperative morbidity. Unfortunately, the follow-up of resected patients is far from being optimal and there is a lack of consensus on recommendations with regard to timing and methods of surveillance. Here, we summarize the current knowledge on the postoperative surveillance of neoplastic pancreatic cysts, focusing on the mechanisms and risk factors for recurrence, the recurrence rates according to the initial indication for surgery, the final result of the surgical specimen and neoplastic risk in the remaining pancreas, as well as the postsurgical morbidity comprising pancreatic exocrine insufficiency, metabolic dysfunction and diabetes after resection, according to the type of surgery performed. We analyze postsurgical recurrence rates and morbidity profiles, as influenced by different surgical techniques, to better delineate at-risk patients, and highlight the need for tailored surveillance strategies adapted to preoperative and operative factors with an impact on outcomes.
PubMed: 38786354
DOI: 10.3390/diagnostics14101056 -
Journal of Cytology 2024The Papanicolaou Society of Cytopathology System for reporting Pancreaticobiliary Cytology (PSCPC) is a reliable method to classify pancreatic fine needle aspiration...
INTRODUCTION
The Papanicolaou Society of Cytopathology System for reporting Pancreaticobiliary Cytology (PSCPC) is a reliable method to classify pancreatic fine needle aspiration cytology (FNAC) smears. However, it is not without practical problems which can diminish the diagnostic accuracy of the cytological diagnosis.
AIMS AND OBJECTIVES
To determine the diagnostic pitfalls while reporting cytomorphology of pancreatic lesions according to PSCPC on correlating FNAC findings with histopathology.
MATERIALS AND METHODS
Retrospective analysis of pancreatic FNAC smears received in the Department of Pathology of our tertiary care institute over a period of 2 years was done. The cytological diagnoses were classified according to the Papanicolaou Society of Cytopathology system of reporting pancreaticobiliary cytology and correlated with histopathology. The reasons of cyto-histological discordance were analyzed.
RESULTS
Out of 50 cases in which both FNAC and biopsy of pancreatic lesions were done, 34 cases were positive/malignant (Category VI), eight cases were suspicious for malignancy (Category V), three cases were neoplastic (Category IV), two cases were atypical (Category III), two cases were negative for malignancy (Category II), and one case was non-diagnostic (Category I). Out of 50 cases, histopathology was non-diagnostic due to inadequate material in six cases. The cytological diagnoses were compared with histopathology in the remaining 44 cases. Categories III, IV V, and VI were considered as positive for neoplastic pathology. The sensitivity of FNAC to predict neoplastic pathology was 97.5%, while the specificity was 25%. The positive predictive value was 92.9%. Two cases reported as atypical (Category III) turned out to be adenocarcinoma on histopathology. One case reported as neuroendocrine tumor and two cases reported as adenocarcinoma on cytology displayed features of chronic pancreatitis on histology. One case reported as neoplastic mucinous cyst (Category IV) turned out to be adenocarcinoma on histology (limited concordance).
CONCLUSION
The cytopathologist needs to be wary of the potential pitfalls to improve the diagnostic accuracy of FNACs.
PubMed: 38779600
DOI: 10.4103/joc.joc_90_23 -
Hepatocellular carcinoma presenting as an extrahepatic mass: A case report and review of literature.World Journal of Gastrointestinal... May 2024Hepatocellular carcinoma (HCC) is a primary liver tumor generally diagnosed based on radiographic findings. Metastatic disease is typically associated with increased...
BACKGROUND
Hepatocellular carcinoma (HCC) is a primary liver tumor generally diagnosed based on radiographic findings. Metastatic disease is typically associated with increased tumor diameter, multifocality, and vascular invasion. We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography (CT). We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.
CASE SUMMARY
A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval, mixed cystic-solid mass. Serial CT evaluations demonstrated steatosis, but no cirrhosis or liver lesions. Endoscopic ultrasound demonstrated a normal-appearing pancreas, biliary tree, and liver. Fine needle aspiration yielded atypical cells. The differential diagnosis included duodenal or pancreatic cyst, lymphoproliferative cyst, stromal or mesenchymal lesions, nodal involvement from gastrointestinal or hematologic malignancy, or duodenal gastro-intestinal stromal tumor. After review by a multidisciplinary tumor board, the patient underwent open surgical resection of a 5.2 cm × 5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC. Magnetic resonance imaging (MRI) subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement, fatty sparing, and intrinsic T1 hyperintensity. Alpha fetoprotein was 23.3 ng/mL. The patient was diagnosed with HCC with portocaval nodal involvement. Review: We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC. We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions, and 30 cases of extrahepatic HCC found to be primary, ectopic HCC.
CONCLUSION
Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary. In patients with risk factors for HCC and lesions suspicious for metastatic disease, MRI may be integral to identifying small hepatic lesions and differentiating from ectopic HCC. Tumor markers may also have utility in establishing the diagnosis.
PubMed: 38764834
DOI: 10.4251/wjgo.v16.i5.2241 -
Abdominal Radiology (New York) May 2024To perform a comparative analysis of surgically resected mucinous cystic neoplasm (MCN) of pancreas and branch-duct type intraductal papillary mucinous neoplasms...
Comparison with surgically resected mucinous cystic neoplasm of pancreas and branch-duct type intraductal papillary mucinous neoplasm considering clinico-radiological high-risk features: a reassessment of current guidelines.
PURPOSE
To perform a comparative analysis of surgically resected mucinous cystic neoplasm (MCN) of pancreas and branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) considering clinico-radiological high-risk predictors for malignant tumors using the current management guidelines.
MATERIALS AND METHODS
224 patients who underwent surgical resection and had histopathologically confirmed MCNs (benign 73; malignant 17) or BD-IPMNs (benign 110; malignant 24) and had pre-operative CT or MRI were retrospectively reviewed. Tumors classified as either high-grade dysplasia or invasive carcinoma were considered malignant, whereas those with low-grade dysplasia were considered benign. Imaging features were analyzed by two radiologists based on selected high-risk stigmata or worrisome features proposed by prevalent guidelines except tumors with main pancreatic duct dilatation (> 5 mm) were excluded.
RESULTS
MCNs and BD-IPMNs showed significant differences in aspects like tumor size, location, the presence and size of enhancing mural nodules, the presence of wall or septal thickening, and multiplicity. Multivariate analyses revealed tumor size (OR, 1.336; 95% CI, 1.124-1.660, p = 0.002) and the presence of enhancing mural nodules (OR, 67.383; 95% CI, 4.490-1011.299, p = 0.002) as significant predictors of malignant MCNs. The optimal tumor size differentiating benign from malignant tumor was 8.95 cm, with a 70.6% sensitivity, 89% specificity, PPV of 27.6%, and NPV of 96.9%, demonstrating superior specificity than the guideline-suggested threshold of 4.0 cm. For malignant BD-IPMNs, the presence of enhancing mural nodules (OR, 15.804; 95% CI, 4.439-56.274, p < 0.001) and CA 19 - 9 elevation (OR, 19.089; 95%CI, 2.868-127.068, p = 0.002) as malignant predictors, with a size of enhancing mural nodule threshold of 5.5 mm providing the best malignancy differentiation.
CONCLUSION
While current guidelines may be appropriate for managing BD-IPMNs, our results showed a notably larger optimal threshold size for malignant MCNs than that suggested by current guidelines. This warrants reconsidering existing guideline thresholds for initial risk stratification and management of MCNs.
PubMed: 38744705
DOI: 10.1007/s00261-024-04364-y