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Journal of Cystic Fibrosis : Official... May 2024Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety,...
BACKGROUND
Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF.
METHODS
In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight. Because IVA is a sensitive CYP3A substrate and CYP3A maturation is uncertain in infants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements.
RESULTS
Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (-40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed.
CONCLUSIONS
In this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.
Topics: Humans; Cystic Fibrosis; Aminophenols; Quinolones; Infant; Male; Female; Cystic Fibrosis Transmembrane Conductance Regulator; Chloride Channel Agonists; Infant, Newborn; Treatment Outcome
PubMed: 38580563
DOI: 10.1016/j.jcf.2024.03.012 -
Annals of Surgical Oncology Jul 2024Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the... (Meta-Analysis)
Meta-Analysis
Long-Term Oncologic Outcome following Duodenum-Preserving Pancreatic Head Resection for Benign Tumors, Cystic Neoplasms, and Neuroendocrine Tumors: Systematic Review and Meta-analysis.
BACKGROUND
Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the potential to cure patients associated with reduced procedure-related short- and long-term complications.
MATERIALS AND METHODS
Pubmed, Embase, and Cochrane libraries were searched for studies reporting surgery-related complications following PD and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. A total of 38 cohort studies that included data from 1262 patients were analyzed. In total, 729 patients underwent DPPHR and 533 PD.
RESULTS
Concordance between preoperative diagnosis of benign tumors and final histopathology was 90.57% for DPPHR. Cystic and neuroendocrine neoplasms (PNETs) and periampullary tumors (PATs) were observed in 497, 89, and 31 patients, respectively. In total, 34 of 161 (21.1%) patients with intraepithelial papillar mucinous neoplasm exhibited severe dysplasia in the final histopathology. The meta-analysis, when comparing DPPHRt and PD, revealed in-hospital mortality of 1/362 (0.26%) and 8/547 (1.46%) patients, respectively [OR 0.48 (95% CI 0.15-1.58); p = 0.21], and frequency of reoperation of 3.26 % and 6.75%, respectively [OR 0.52 (95% CI 0.28-0.96); p = 0.04]. After a follow-up of 45.8 ± 26.6 months, 14/340 patients with intraductal papillary mucinous neoplasms/mucinous cystic neoplasms (IPMN/MCN, 4.11%) and 2/89 patients with PNET (2.24%) exhibited tumor recurrence. Local recurrence at the resection margin and reoccurrence of tumor growth in the remnant pancreas was comparable after DPPHR or PD [OR 0.94 (95% CI 0.178-5.34); p = 0.96].
CONCLUSIONS
DPPHR for benign, premalignant neoplasms provides a cure for patients with low risk of tumor recurrence and significantly fewer early surgery-related complications compared with PD. DPPHR has the potential to replace PD for benign, premalignant cystic and neuroendocrine neoplasms.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Pancreaticoduodenectomy; Duodenum; Organ Sparing Treatments; Pancreatic Cyst; Postoperative Complications; Prognosis; Pancreatectomy
PubMed: 38578553
DOI: 10.1245/s10434-024-15222-y -
World Journal of Clinical Cases Mar 2024High-grade pancreatic intraepithelial neoplasia (PanIN) exhibits no mass and is not detected by any examination modalities. However, it can be diagnosed by pancreatic...
BACKGROUND
High-grade pancreatic intraepithelial neoplasia (PanIN) exhibits no mass and is not detected by any examination modalities. However, it can be diagnosed by pancreatic juice cytology from indirect findings. Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct (MPD) and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography (ERCP). We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range, but without caudal MPD dilatation on magnetic resonance cholangiopancreatography (MRCP).
CASE SUMMARY
A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision, which revealed pancreatic cysts. MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation. Thus, course observation was performed. After 24 mo, MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst. We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination. We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN. Pancreatic parenchyma invasion was not observed, and curative resection was achieved.
CONCLUSION
High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.
PubMed: 38576815
DOI: 10.12998/wjcc.v12.i8.1487 -
Chirurgie (Heidelberg, Germany) Jun 2024Currently, the most frequently used surgical treatment for symptomatic, benign, premalignant cystic and neuroendocrine neoplasms of the pancreatic head is the Whipple... (Review)
Review
Currently, the most frequently used surgical treatment for symptomatic, benign, premalignant cystic and neuroendocrine neoplasms of the pancreatic head is the Whipple procedure or pylorus-preserving pancreatoduodenectomy (PD). However, when performed for treatment of benign tumors, PD is a multiorgan resection involving loss of pancreatic and extrapancreatic tissue and functions. PD for benign neoplasm is associated with the risk of considerable early postoperative complications and an in-hospital mortality of up to 5%. Following the Whipple procedure a new onset of diabetes mellitus is observed in 14-20% and new exocrine insufficiency in 25-45%, leading to metabolic dysfunction and impairment of quality of life persisting after resection of benign tumors. Symptomatic neoplasms are indication for surgery. Patients with asymptomatic pancreatic tumors are treated according to the criteria of surveillance protocols. The goal of surgical treatment for asymptomatic patients is, according to the guideline criteria, interruption of the surveillance program before the development of an advanced stage cancer associated with the neoplasm. Tumor enucleation and duodenum-preserving pancreatic head resection, either total or partial, are parenchyma-sparing resections for benign neoplasms of the pancreatic head. The first choice for small tumors is enucleation; however, enucleation is associated with an increased risk of pancreatic fistula B + C following pancreatic main duct injury. Duodenum-preserving total or partial pancreatic head resection has the advantage of low postoperative surgery-related complications, a mortality of < 0.5% and maintenance of the endocrine and exocrine pancreatic functions. Parenchyma-sparing pancreatic head resections should replace classical Whipple procedures for neoplasms of the pancreatic head.
Topics: Humans; Pancreatic Neoplasms; Pancreaticoduodenectomy; Neuroendocrine Tumors; Precancerous Conditions; Pancreatic Cyst; Postoperative Complications
PubMed: 38568302
DOI: 10.1007/s00104-024-02070-5 -
ACG Case Reports Journal Apr 2024Spontaneous tumor lysis syndrome (STLS) secondary to metastatic pancreatic adenocarcinoma is a rare clinical phenomenon. An 86-year-old woman with a history of...
Spontaneous tumor lysis syndrome (STLS) secondary to metastatic pancreatic adenocarcinoma is a rare clinical phenomenon. An 86-year-old woman with a history of pancreatic cysts presented to the emergency department with progressive fatigue, transaminitis, elevated lactate dehydrogenase, and acute kidney injury of unclear etiology. Abdominal imaging and celiac lymph node biopsy were consistent with metastatic pancreatic adenocarcinoma. Her clinical status deteriorated requiring intensive care unit transfer, and her laboratory results were found to be consistent with STLS. Despite treatment, she entered multisystem organ failure and died shortly after. This case adds to the literature of STLS in pancreatic adenocarcinomas.
PubMed: 38560013
DOI: 10.14309/crj.0000000000001305 -
Surgical Case Reports Apr 2024Pancreatic adenosquamous cell carcinoma (PASC) is a relatively rare histological type of pancreatic malignancy, and preoperative diagnosis is difficult because of its...
BACKGROUND
Pancreatic adenosquamous cell carcinoma (PASC) is a relatively rare histological type of pancreatic malignancy, and preoperative diagnosis is difficult because of its rarity. PASC accounts for 1-4% of all pancreatic cancers, and even after curative surgery, its prognosis is poorer than that of ordinary pancreatic adenocarcinoma. Pathologically, it shows glandular and squamous differentiation of cells. Complete resection is the only method to achieve a good long-term prognosis, and an increasing doubling time of PASC is considered to indicate early recurrence after surgery. Here, we report a rare case of PASC with an infected pancreatic cyst that was difficult to treat, along with a review of the literature.
CASE PRESENTATION
A woman in her 80s with a history of breast cancer presented with pericardial pain. Computed tomography revealed a 20-mm hypovascular tumor in the body of the pancreas and a 27-mm pseudocyst. Endoscopic retrograde cholangiopancreatography showed a severe main pancreatic duct stenosis in the body of the pancreas that made cannulation impossible, and contrast media extravasation was due to pancreatic duct disruption in the pancreatic tail. Endoscopic fine-needle aspiration revealed that the tumor was a PASC. Because the patient had an infected pancreatic cyst, central intravenous nutrition and antibiotics were administered, which stabilized her general condition. She was diagnosed with resectable PASC and underwent distal pancreatectomy with lymphadenectomy. The postoperative course was uneventful. Immunohistochemical analysis of the resected specimen confirmed T2N0M0 stage IB. Systemic adjuvant chemotherapy with S-1 is ongoing.
CONCLUSION
Appropriate preoperative management and preoperative accurate staging (T2N0M0 stage IB) of PASC with curative surgery can ensure predictable outcomes.
PubMed: 38557796
DOI: 10.1186/s40792-024-01868-z -
Journal of Gastrointestinal and Liver... Mar 2024Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose...
BACKGROUND AND AIMS
Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer.
METHODS
Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed.
RESULTS
Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919).
CONCLUSIONS
The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.
Topics: Humans; Adult; Pancreatic Cyst; Carcinoembryonic Antigen; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Pancreas; Glucose; Pancreatic Neoplasms
PubMed: 38554431
DOI: 10.15403/jgld-5330 -
Cureus Feb 2024Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disease. Diagnosis of ADPKD is usually made by the number of renal cysts on the ultrasound for...
Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disease. Diagnosis of ADPKD is usually made by the number of renal cysts on the ultrasound for each age category. There are two types of ADPKD, and the patients with the second type have later onset of symptoms, with slower disease progression than in the first type. These patients are typically at risk of recurrent urinary tract infections, hemorrhage and rupture of cysts, end-stage renal disease, calculi, liver/pancreatic cysts, and brain aneurysm development.
PubMed: 38550415
DOI: 10.7759/cureus.55072 -
International Journal of Molecular... Mar 2024Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new...
Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1β) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1β, glucose, and CEA, and serum for Ngal and IL-1β. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1β and serum Ngal made no diagnostic contribution.
Topics: Humans; Carcinoembryonic Antigen; Glucose; Lipocalin-2; Pancreatic Cyst; Pancreatic Neoplasms; Prospective Studies
PubMed: 38542201
DOI: 10.3390/ijms25063224 -
Cancers Mar 2024Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2030, yet there is a lack of accurate diagnostic tests for early detection.... (Review)
Review
Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2030, yet there is a lack of accurate diagnostic tests for early detection. Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer and are increasingly being detected. Despite the development and refinement of multiple guidelines, diagnosing high-grade dysplasia or cancer in IPMNs using clinical, radiologic, endosonographic, and cyst fluid features still falls short in terms of accuracy, leading to both under- and overtreatment. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel technology that allows real-time optical biopsies of pancreatic cystic lesions. Emerging data has demonstrated that EUS-nCLE can diagnose and risk stratify IPMNs more accurately than conventional diagnostic tools. Implementing EUS-nCLE in clinical practice can potentially improve early diagnosis of pancreatic cancer, reduce unnecessary surgeries of IPMNs with low-grade dysplasia, and advance the field of digital pathomics. In this review, we summarize the current evidence that supports using EUS-nCLE as a diagnostic imaging biomarker for diagnosing IPMNs and for risk stratifying their degree of neoplasia. Moreover, we will present emerging data on the role of adding artificial intelligence (AI) algorithms to nCLE and integrating novel fluid biomarkers into nCLE.
PubMed: 38539568
DOI: 10.3390/cancers16061238