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Iranian Journal of Medical Sciences Feb 2024Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic... (Review)
Review
BACKGROUND
Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic review, we evaluated and studies on the effect of inhibition or activation of the Shh pathway on the production, differentiation, maintenance, and endocrine activity of IPCs.
METHODS
A systematic review was conducted using all available experimental studies published between January 2000 and November 2022. The review aimed at determining the effect of Shh manipulation on the differentiation of stem cells (SCs) into IPCs. Keywords and phrases using medical subject headings were extracted, and a complete search was performed in Web of Science, Embase, ProQuest, PubMed, Scopus, and Cochrane Library databases. The inclusion criteria were manipulation of Shh in SCs, SCs differentiation into IPCs, and endocrine activity of mature IPCs. Articles with incomplete data and duplications were excluded.
RESULTS
A total of 208 articles were initially identified, out of which 11 articles were included in the study. The effect of Shh inhibition in the definitive endoderm stage to produce functional IPCs were confirmed. Some studies showed the importance of Shh re-activation at late-stage differentiation for the generation of efficient IPCs. It is proposed that baseline concentrations of Shh in mature pancreatic β-cells affect insulin secretion and endocrine activities of the cells. However, Shh overexpression in pancreatic β-cells ultimately leads to improper endocrine function and inadequate glucose-sensing insulin secretion.
CONCLUSION
Accurate manipulation of the Shh signaling pathway can be an effective approach in the production and maintenance of functional IPCs.
Topics: Hedgehog Proteins; Insulin; Cell Differentiation; Signal Transduction; Insulin-Secreting Cells
PubMed: 38356490
DOI: 10.30476/ijms.2023.95425.2678 -
Anatomy & Cell Biology Mar 2024The exocrine part of the pancreas has a duct system called the pancreatic ductal system (PDS). Its mechanism of development is complex, and any reorganization during...
The exocrine part of the pancreas has a duct system called the pancreatic ductal system (PDS). Its mechanism of development is complex, and any reorganization during early embryogenesis can give rise to anatomical variants. The aim of this study is to collect, classify, and analyze published evidence on the importance of anatomical variants of the PDS, addressing gaps in our understanding of such variations. The MEDLINE, Web of Science, Embase, and Google Scholar databases were searched to identify publications relevant to this review. R studio with meta-package was used for data extraction, risk of bias estimation, and statistical analysis. A total of 64 studies out of 1,778 proved suitable for this review and metanalysis. The meta-analysis computed the prevalence of normal variants of the PDS (92% of 10,514 subjects). Type 3 variants and "descending" subtypes of the main pancreatic duct (MPD) predominated in the pooled samples. The mean lengths of the MPD and accessory pancreatic duct (APD) were 16.53 cm and 3.36 cm, respectively. The mean diameters of the MPD at the head and the APD were 3.43 mm and 1.69 mm, respectively. The APD was present in only 41% of samples, and the long type predominated. The pancreatic ductal anatomy is highly variable, and the incorrect identification of variants may be challenging for surgeons during ductal anastomosis with gut, failure to which may often cause ductal obstruction or pseudocysts formation.
PubMed: 38351473
DOI: 10.5115/acb.23.148 -
Endoscopy International Open Feb 2024Recent advances in endoscopic transmural treatment have improved the clinical outcomes of patients with pancreatic fluid collections (PFCs). However, there is still a... (Review)
Review
Recent advances in endoscopic transmural treatment have improved the clinical outcomes of patients with pancreatic fluid collections (PFCs). However, there is still a debate about the preventive effect of long-term placement of a transmural plastic stent (PS) on recurrence after successful endoscopic ultrasound (EUS)-guided treatment of PFCs. We conducted a systematic review and meta-analysis to evaluate PFC recurrence rates with and without a transmural PS after EUS-guided treatment. A systematic literature search of PubMed, Embase, and the Cochrane database was conducted to identify clinical studies comparing outcomes with and without transmural PS published until September 2022. Data on PFC recurrence and adverse events (AEs) were pooled using a random-effects model. Nine studies including 380 patients with long-term transmural PS and 289 patients without PS were identified. The rate of PFC recurrence was significantly lower in patients with transmural PS (pooled odds ratio [OR] = 0.23, 95% confidence interval [CI] [0.08-0.65], = 0.005). In a subgroup analysis limited to studies focusing on patients with disconnected pancreatic duct syndrome, which has been reported to be a risk factor for PFC recurrence, the OR was numerically lower than that for the entire cohort (OR = 0.14, 95% CI [0.04-0.46]). The rate of AEs was significantly higher with long-term transmural PS (OR = 14.77, 95% CI [4.21-51.83]). In this meta-analysis, long-term PS placement reduced the risk of PFC recurrence. Given the potential AEs of indwelling PS, further research is required to evaluate the overall benefits of long-term PS placement.
PubMed: 38348330
DOI: 10.1055/a-2226-1237 -
Seminars in Nuclear Medicine Mar 2024The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a... (Review)
Review
The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a theranostic framework. Various radioligands targeting GRPR have undergone investigation in preclinical and clinical studies related to breast cancer. This systematic scoping review aimed to assess the current evidence on GRPR-targeted radioligands for diagnostic and therapeutic applications in breast cancer. The methodology followed the PRISMA-ScR protocol. The literature search was conducted in September 2023 and encompassed MEDLINE, Embase, Cochrane, and Scopus databases. We included original peer-reviewed studies focused on breast cancer patients or in vivo breast cancer models. Two reviewers performed the study selection process independently. Data were extracted, synthesized, and categorized into preclinical and clinical studies, further subdivided based on radioligand properties. A total of 35 original studies were included in the review, with three of them evaluating therapeutic outcomes. The results indicated that GRPR-radioantagonists are superior to GRPR-agonists, exhibiting preferable in vivo stability, rapid, specific tumor targeting, and enhanced retention. Both preclinical and clinical evaluations demonstrated renal excretion and high uptake in normal GRPR-expressing tissue, primarily the pancreas. A significant positive correlation was observed between GRPR and estrogen-receptor expression. In the clinical setting, GRPR-radioligands effectively detected primary tumors and, to a lesser extent, lymph node metastases. Moreover, GRPR-targeted radioantagonists successfully identified distant metastases originating from various sites in advanced metastatic disease, strongly correlated with positive estrogen receptor expression. Preclinical therapeutic evaluation of GRPR-radioligands labeled with lutetium-177 showed promising tumor responses, and none of the studies reported any observed or measured side effects, indicating a safe profile. In conclusion, the evidence presented in this review indicates a preference for GRPR-targeted antagonists over agonists, owing to their superior kinetics and promising diagnostic potential. Clinical assessments suggested diagnostic value for GRPR-targeted theranostics in breast cancer patients, particularly those with high estrogen receptor expression. Nevertheless, in the therapeutic clinical context, paying attention to the radiation dose administered to the pancreas and kidneys is crucial.
Topics: Humans; Female; Receptors, Bombesin; Breast Neoplasms; Precision Medicine; Receptors, Estrogen
PubMed: 38342656
DOI: 10.1053/j.semnuclmed.2024.01.004 -
Journal of Clinical Medicine Jan 2024Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies... (Review)
Review
Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.
PubMed: 38337524
DOI: 10.3390/jcm13030830 -
Journal of Gastrointestinal Cancer Jun 2024GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon,... (Review)
Review
PURPOSE
GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature.
METHODS
A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed.
RESULTS
The median age of patients treated at our centre was 53 years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74 months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%.
CONCLUSION
Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.
Topics: Humans; Gastrointestinal Stromal Tumors; Middle Aged; Pancreatic Neoplasms; Female; Male; Aged; Adult
PubMed: 38324136
DOI: 10.1007/s12029-024-01024-8 -
World Journal of Radiology Jan 2024After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated the feasibility as well as...
BACKGROUND
After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated the feasibility as well as diagnostic capabilities of liver, kidney, and prostate MRI at 7-Tesla. However, the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks, primarily stemming from heightened artifacts and limitations in Specific Absorption Rate, Furthermore, evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence.
AIM
To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends, details relevant challenges, and provides a concise set of potential solutions.
METHODS
This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A PubMed search, utilizing Medical Subject Headings terms such as "7-Tesla" and organ-specific terms, was conducted for articles published between January 1, 1985, and July 25, 2023. Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs, encompassing various study types (/, method development, reviews/meta-analyses). Exclusion criteria involved animal studies and those lacking extractable data. Study selection involved initial identification title/abstract, followed by a full-text review by two researchers, with discrepancies resolved through discussion. Data extraction covered publication details, study design, population, sample size, 7T MRI protocol, image characteristics, endpoints, and conclusions.
RESULTS
The systematic review included a total of 21 studies. The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate ( = 8), followed by the kidney ( = 6) and the hepatobiliary system ( = 5). Studies on these organs, and in the pancreas, demonstrated clear advantages at 7T. However, small bowel studies showed no significant improvements compared to traditional MRI at 1.5T. The majority of studies evaluated originated from Germany ( = 10), followed by the Netherlands ( = 5), the United States ( = 5), Austria ( = 2), the United Kingdom ( = 1), and Italy ( = 1).
CONCLUSION
Further increase of abdominal clinical MRI field strength to 7T demonstrated high imaging potential, yet also limitations mainly due to the inhomogeneous radiofrequency (RF) excitation field relative to lower field strengths. Hence, further optimization of dedicated RF coil elements and pulse sequences are expected to better optimize clinical imaging at high magnetic field strength.
PubMed: 38312348
DOI: 10.4329/wjr.v16.i1.20 -
Clinical Transplantation Jan 2024Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound... (Review)
Review
Transplantation surgery continues to evolve and improve through advancements in transplant technique and technology. With the increased availability of ultrasound machines as well as the continued development of Enhanced Recovery after Surgery (ERAS) protocols, regional anesthesia has become an essential component of providing analgesia and minimizing opioid use perioperatively. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. To date, no formal guidelines or recommendations exist which address the use of regional anesthesia in transplantation surgery. In response, the Society for the Advancement of Transplant Anesthesia (SATA) identified experts in both transplantation surgery and regional anesthesia to review available literature concerning these topics. The goal of this task force was to provide an overview of these publications to help guide transplantation anesthesiologists in utilizing regional anesthesia. The literature search encompassed most transplantation surgeries currently performed and the multitude of associated regional anesthetic techniques. Outcomes analyzed included analgesic effectiveness of the blocks, reduction in other analgesic modalities-particularly opioid use, improvement in patient hemodynamics, as well as associated complications. The findings summarized in this systemic review support the use of regional anesthesia for postoperative pain control after transplantation surgeries. Part 1 of the manuscript focused on regional anesthesia performed in thoracic transplantation surgeries, and part 2 in abdominal transplantations. Specifically, regional anesthesia in liver, kidney, pancreas, intestinal, and uterus transplants or applicable surgeries are discussed.
Topics: Female; Humans; Analgesics, Opioid; Pain, Postoperative; Anesthesia, Conduction; Abdominal Muscles; Analgesics
PubMed: 38289879
DOI: 10.1111/ctr.15227 -
Journal of Hepato-biliary-pancreatic... May 2024This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged... (Meta-Analysis)
Meta-Analysis Review
Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.
BACKGROUND
This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD).
METHODS
Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years).
RESULTS
IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group.
CONCLUSION
ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.
Topics: Humans; Pancreaticoduodenectomy; Aged; Enhanced Recovery After Surgery; Aged, 80 and over; Length of Stay; Postoperative Complications; Age Factors; Recovery of Function; Female; Male; Patient Readmission
PubMed: 38282543
DOI: 10.1002/jhbp.1417 -
Annals of Surgery Jun 2024Through a systematic review and spline curve analysis, to better define the minimum volume threshold for hospitals to perform (pancreaticoduodenectomy) and the...
OBJECTIVE
Through a systematic review and spline curve analysis, to better define the minimum volume threshold for hospitals to perform (pancreaticoduodenectomy) and the high-volume center.
BACKGROUND
The pancreaticoduodenectomy (PD) is a resource-intensive procedure, with high morbidity and long hospital stays resulting in centralization towards high-volume hospitals; the published definition of high volume remains variable.
MATERIALS AND METHODS
Following a systematic review of studies comparing PD outcomes across volume groups, semiparametric regression modeling of morbidity (%), mortality (%), length of stay (days), lymph node harvest (number of nodes), and cost ($USD) as continuous variables were performed and fitted as a smoothed function of splines. If this showed a nonlinear association, then a "zero-crossing" technique was used, which produced "first and second derivatives" to identify volume thresholds.
RESULTS
Our analysis of 33 cohort studies (198,377 patients) showed 55 PDs/year and 43 PDs/year were the threshold value required to achieve the lowest morbidity and highest lymph node harvest, with model estimated df 5.154 ( P <0.001) and 8.254 ( P <0.001), respectively. The threshold value for mortality was ~45 PDs/year (model 9.219 ( P <0.001)), with the lowest mortality value (the optimum value) at ~70 PDs/year (ie, a high-volume center). No significant association was observed for cost ( edf =2, P =0.989) and length of stay ( edf =2.04, P =0.099).
CONCLUSIONS
There is a significant benefit from the centralization of PD, with 55 PDs/year and 43 PDs/year as the threshold value required to achieve the lowest morbidity and highest lymph node harvest, respectively. To achieve mortality benefit, the minimum procedure threshold is 45 PDs/year, with the lowest and optimum mortality value (ie, a high-volume center) at approximately 70 PDs/year.
Topics: Humans; Centralized Hospital Services; Hospitals, High-Volume; Length of Stay; Pancreatic Neoplasms; Pancreaticoduodenectomy; Regression Analysis
PubMed: 38258578
DOI: 10.1097/SLA.0000000000006208