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Clinical Oncology (Royal College of... May 2024Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the...
AIMS
Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC.
MATERIALS AND METHODS
This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0-3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated.
RESULTS
55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5-37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0-1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3-18.7). Median OS post diagnosis was 19 months (95% CI 15.9-22.1). One-year local control post SMART was 65%.
CONCLUSION
This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes.
PubMed: 38902119
DOI: 10.1016/j.clon.2024.05.012 -
International Journal of Pharmaceutics Jun 2024In this part, drug concentration in blood after ingesting slow-release gastroretentive fibrous dosage forms and immediate-release particulate forms is modeled. The...
In this part, drug concentration in blood after ingesting slow-release gastroretentive fibrous dosage forms and immediate-release particulate forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Eventually, the elimination and absorption rates will be equal, and the drug concentration in blood plateaus out. After the gastric residence time drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering an immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.
PubMed: 38901538
DOI: 10.1016/j.ijpharm.2024.124362 -
World Journal of Clinical Cases Jun 2024Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR)....
BACKGROUND
Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR.
AIM
To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors.
METHODS
A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed.
RESULTS
There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference ( < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation.
CONCLUSION
Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.
PubMed: 38899293
DOI: 10.12998/wjcc.v12.i16.2738 -
Nutrients May 2024The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies,...
BACKGROUND
The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful.
OBJECTIVES
To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD.
METHODS
All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano's diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected.
RESULTS
A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology.
CONCLUSIONS
The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient.
Topics: Celiac Disease; Humans; Female; Male; Adult; Immunophenotyping; Middle Aged; Duodenum; Flow Cytometry; Intraepithelial Lymphocytes; Biopsy; Aged; Young Adult; Diet, Gluten-Free
PubMed: 38892566
DOI: 10.3390/nu16111633 -
Transplantation Proceedings Jun 2024The swine is a valuable model for preclinical research and surgical technique training. Induction of Type I diabetes is achieved by total pancreatectomy, therefore these...
BACKGROUND
The swine is a valuable model for preclinical research and surgical technique training. Induction of Type I diabetes is achieved by total pancreatectomy, therefore these animals may be used in several research studies, including islet transplantation field. Given the lack of information in the literature, the purpose of this work is to describe anatomic aspects of swine pancreas, the total pancreatectomy surgical technique, intra- and postoperative complications and the autopsy results.
MATERIAL AND METHODS
Five hybrid male pigs, 20-35 kg, submitted to total pancreatectomy with duodenum, bile duct, and spleen preservation. Postoperatively, daily clinical assessment and capillary blood glucose collection were performed. At the end of the 30-day period or in the occurrence of serious clinical complications, euthanasia and autopsy were performed.
RESULTS
The average duration of surgery was 128 minutes, without intraoperative deaths or anesthesia induction failures. The median survival was 6.6 days. Postoperative complications were weight loss (3), emesis (2), constipation (2), abdominal distension (2), diarrhea (1), and loss of appetite (1). All animals were euthanized due to serious complications. Two animals presented surgical complications (duodenal necrosis with gastroparesis and internal hernia with intestinal necrosis). The other 3 animals presented serious clinical complications related to exocrine pancreatic insufficiency due to deficiency of pancreatic enzymes. Glycemic values above 200 mg/dL were found on the first postoperative day and above 300 mg/dL on the seventh day in all animals.
CONCLUSION
A model of total pancreatectomy with duodenum, spleen, and bile duct preservation in pigs was established. All animals became diabetic, however, animals without postoperative complications were euthanized due to serious complications related to pancreas exocrine insufficiency.
PubMed: 38890075
DOI: 10.1016/j.transproceed.2024.04.020 -
Annals of Surgical Oncology Jun 2024Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal...
BACKGROUND
Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior.
METHODS
This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC.
RESULTS
Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size.
CONCLUSIONS
Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
PubMed: 38888860
DOI: 10.1245/s10434-024-15555-8 -
Indian Journal of Otolaryngology and... Jun 2024Pharyngitis is an inflammation of the mucous membranes of the oropharynx. Pharyngitis may be caused by an infectious or noninfectious disease. Noninfectious diseases of...
Pharyngitis is an inflammation of the mucous membranes of the oropharynx. Pharyngitis may be caused by an infectious or noninfectious disease. Noninfectious diseases of pharynx include allergies, trauma, cancer, reflux and certain toxins. Infection with H. Pylori is associated with developing chronic sore throat, gastritis, gastric or duodenal ulcer, gastric cancer and MALT lymphoma. There are many different investigations to diagnose H pylori as H pylori antigen in blood and stool, urea breath test but, H. Pylori line is a new test for detection of the virulent strains. There are many lines of H pylori therapy in the form of PPIs and antibiotics for about two weeks. This study aimed to detect role of H pylori in chronic pharyngitis. 85 patients who had chronic pharyngitis with normal CBC, WBCS, lymphocyte, monocyte and eosinophils with negative ASO titer and throat swab. These patients did H pylori line to detect H pylori virulent antigen. 77 patients with chronic pharyngitis are positive H pylori and after medical treatment 68 patients became negative. H. Pylori line is a new test for detection of the virulent strains and screening H pylori carrier at risk of developing gastric and duodenal ulcers as well as cancer.
PubMed: 38883532
DOI: 10.1007/s12070-024-04556-4 -
Frontiers in Medicine 2024Renal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often...
BACKGROUND
Renal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often misdiagnosed as malignant renal tumors with abundant blood supply, and the definitive diagnosis primarily relies on angiography. Multimodality imaging, including contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT plays an important role in the differential diagnosis of renal space-occupying lesions.
CASE PRESENTATION
A 56-year-old man presented with abdominal distension, loss of appetite, and back pain without obvious cause 2 years ago, without nausea vomiting, or frequent urination. Gastroscopy and colonoscopy showed multiple polyps in the duodenum and colon. Abdomen contrast-enhanced CT revealed a mass of 1.6 × 1.4 cm in the left kidney, which was considered to be a malignant tumor. PET/CT was performed for further diagnosis; the F-fluorodesoxyglucose (F-FDG) PET/CT scan showed mild uptake in the left renal mass, while no uptake of F- prostate-specific membrane antigen (PSMA) was observed. Following a multidisciplinary discussion, the possibility of renal AVMs was considered and subsequently confirmed by renal angiography as the diagnosis. Then, selective segmental renal artery embolization was performed for treatment.
CONCLUSION
Renal AVMs are extremely rare in clinical practice. Due to limited research on the application of F-FDG and F-PSMA PET/CT to renal AVMs, its role remains largely unexplored. With the increasing popularity of PET/CT imaging, comprehensive imaging of the disease has become indispensable. We report the first case of PSMA PET/CT imaging in renal AVMs, and when PSMA expression is absent in a renal mass, the possibility of renal AVMs should be considered.
PubMed: 38882665
DOI: 10.3389/fmed.2024.1420473 -
European Journal of Nuclear Medicine... Jun 2024F-labelled somatostatin receptor (SSTR) analogs offer several advantages over Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an...
Evaluation of the safety, biodistribution, dosimetry of [F]AlF-NOTA-LM3 and head-to-head comparison with [Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.
PURPOSE
F-labelled somatostatin receptor (SSTR) analogs offer several advantages over Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [Ga]Ga-DOTATATE or [Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs.
METHODS
Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [Ga]Ga-DOTATATE and [F]AlF-NOTA-LM3 was compared.
RESULTS
[F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [F]AlF-NOTA-LM3 was significantly lower than that of [Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [F]ALF-NOTA-LM3 were significantly smaller than those detected on [Ga]Ga-DOTATATE.
CONCLUSION
[F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [Ga]Ga-DOTATATE.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT06056362.
PubMed: 38878175
DOI: 10.1007/s00259-024-06790-y -
Clinical Endoscopy Jun 2024Advanced pancreatic and biliary tract cancers can invade the duodenum and cause duodenal hemorrhagic stenosis. This study aimed to evaluate the efficacy of covered...
BACKGROUND/AIMS
Advanced pancreatic and biliary tract cancers can invade the duodenum and cause duodenal hemorrhagic stenosis. This study aimed to evaluate the efficacy of covered self-expandable metal stents in the treatment of cancer-related duodenal hemorrhage with stenosis.
METHODS
Between January 2014 and December 2016, metal stents were placed in 51 patients with duodenal stenosis. Among these patients, a self-expandable covered metal stent was endoscopically placed in 10 patients with hemorrhagic duodenal stenosis caused by pancreatobiliary cancer progression. We retrospectively analyzed the therapeutic efficacy of the stents by evaluating the technical and clinical success rates based on successful stent placement, degree of oral intake, hemostasis, stent patency, and overall survival.
RESULTS
The technical and clinical success rates were 100%. All 10 patients achieved a Gastric Outlet Obstruction Scoring System score of three within two weeks after the procedure and had no recurrence of melena. The median stent patency duration and overall survival after stent placement were 52 days (range, 20-220 days) and 66.5 days (range, 31-220 days), respectively.
CONCLUSIONS
Endoscopic placement of a covered metal stent for hemorrhagic duodenal stenosis associated with pancreatic or biliary tract cancer resulted in duodenal hemostasis, recanalization, and improved quality of life.
PubMed: 38872407
DOI: 10.5946/ce.2023.155