-
Hepatobiliary Surgery and Nutrition Jun 2024The establishment of preoperative chemotherapy (PCT) with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with...
BACKGROUND
The establishment of preoperative chemotherapy (PCT) with FOLFIRINOX and gemcitabine/nab-paclitaxel in recent years has enabled resectability in many patients with initially locally advanced pancreatic cancer (LAPC). Nevertheless, information about the impact of PCT on surgical results is scarce.
METHODS
All patients with initial LAPC who received surgery after chemotherapy at the high-volume centre for pancreatic surgery of St. Josef-Hospital Bochum between 2015 and 2022 were included in this retrospective cohort analysis.
RESULTS
A total of 139 patients underwent surgery after pre-treatment with FOLFIRINOX (76.3%), gemcitabine/nab-paclitaxel (11.5%), both (5.8%) and other regimens (6.5%). Eighty-five tumors (61.2%) were resectable after PCT. R0 resection was achieved in 92.9%, R1 in 7.1% and R2 in 0% of cases. Fifty-four tumors were still not resectable at the time of surgery. Surgical results of the patients did not show increased postoperative mortality and morbidity compared to the literature data. Postoperative 30-day mortality was 1.4%. Rates for pancreas-specific complications [postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and others] were not increased. POPF occurred in 10.5% and DGE in 26.3% after pancreaticoduodenectomy. After distal pancreatectomy, POPF was detected in 37.5% and DGE in 12.5%. Median postoperative survival (31 13 months) and overall survival after initial diagnosis (40 20 months) were significantly longer in resected patients (P<0.001). Postoperative recurrence-free survival in resected patients amounted to 12 months.
CONCLUSIONS
This study underlines that PCT allows resectability of primarily unresectable patients with LAPC without increasing perioperative mortality and morbidity. It may lead to a significant prolongation of recurrence-free and overall survival in resected patients after PCT.
PubMed: 38911210
DOI: 10.21037/hbsn-23-426 -
Journal of Gastrointestinal Surgery :... Jun 2024Nonsteroidal anti-inflammatory drug (NSAID) use has been investigated as a modifiable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drug (NSAID) use has been investigated as a modifiable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). This study comprises a systematic review and meta-analysis examining the impact of perioperative NSAID use on rates of POPF after PD.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review was performed. Pooled mean differences (MD), odds ratios (OR), and risk ratios with 95% CIs were calculated.
RESULTS
Seven studies published from 2015 to 2021 were included, reporting 2851 PDs (1372 receiving NSAIDs and 1479 not receiving NSAIDs). There were no differences regarding blood loss (MD -99.40 mL; 95% CI, -201.71 to 2.91; P = .06), overall morbidity (OR 1.05; 95% CI, 0.68-1.61; P = .83), hemorrhage (OR 2.35; 95% CI, 0.48-11.59; P = .29), delayed gastric emptying (OR 0.98; 95% CI, 0.60-1.60; P = .93), bile leak (OR 0.68; 95% CI, 0.12-3.89; P = .66), surgical site infection (OR 1.02; 95% CI, 0.33-3.22; P = .97), abscess (OR 0.99; 95% CI, 0.51-1.91; P = .97), clinically relevant POPF (OR 1.18; 95% CI, 0.84-1.64; P = .33), readmission (OR 0.94; 95% CI, 0.61-1.46; P = .78), or reoperation (OR 0.82; 95% CI, 0.33-2.06; P = .68). NSAID use was associated with a shorter hospital stay (MD -1.05 days; 95% CI, -1.39 to 0.71; P < .00001).
CONCLUSION
The use of NSAIDs in the perioperative period for patients undergoing PD was not associated with increased rates of POPF.
PubMed: 38906318
DOI: 10.1016/j.gassur.2024.06.016 -
Clinical Pharmacology in Drug... Jun 2024N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under...
N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under clinical development to treat GNE myopathy, a rare muscle-wasting disease. In this randomized, open-label, 2-sequence, crossover study, 16 healthy women and men were administered a single oral dose of ManNAc under fasting and fed conditions. Blood samples were collected for 48 hours after dosing for quantification of plasma ManNAc and Neu5Ac concentrations. Noncompartmental pharmacokinetic and deconvolution analyses were performed using baseline-corrected plasma concentration data. Administration of ManNAc in the fed state resulted in a 1.6-fold increase in ManNAc exposure, compared to fasting conditions. A concurrent increase in Neu5Ac exposure was observed in the presence of food. Deconvolution analysis indicated that the findings were attributed to prolonged absorption rather than an enhanced rate of absorption. The impact of food on ManNAc pharmacokinetics was greater in women than men (fed/fasted area under the concentration-time curve from time 0 to infinity mean ratio: 198% compared to 121%). It is hypothesized that the presence of food slows gastric emptying, allowing a gradual release of ManNAc into the small intestine, translating into improved ManNAc absorption. The results suggest that taking ManNAc with food may enhance its therapeutic activity and/or reduce the daily dosage requirement.
PubMed: 38899758
DOI: 10.1002/cpdd.1433 -
European Journal of Clinical Nutrition Jun 2024Scientists were chasing an incretin hormone, and when GLP-1 was finally discovered, we found that it had a pronounced satiety effect, slowed down gastric emptying, and... (Review)
Review
Scientists were chasing an incretin hormone, and when GLP-1 was finally discovered, we found that it had a pronounced satiety effect, slowed down gastric emptying, and actually reduced postprandial insulin response. These mechanisms are the basis for the highly efficacious GLP-1 analogues that today offer safe and effective treatment in millions of people living with obesity. Moreover, the combined GLP-1 mechanisms of weight loss and delayed carbohydrate absorption may also be the key drivers of remission of type 2 diabetes and reduced cardiovascular events found by GLP-1 analogues.
PubMed: 38890501
DOI: 10.1038/s41430-024-01460-6 -
Scandinavian Journal of Gastroenterology Jun 2024To observe the clinical therapeutic effect and mental state of mindfulness-based cognitive therapy (MBCT) in patients with functional dyspepsia (FD).
BACKGROUND AND AIM
To observe the clinical therapeutic effect and mental state of mindfulness-based cognitive therapy (MBCT) in patients with functional dyspepsia (FD).
METHODS
In this study, 80 patients suffering from FD in an outpatient clinic were enrolled from January to December 2020. Patients were randomly allocated into the control group (conventional treatment) and observation group (MBCT treatment). Patients in the control group were prescribed rabeprazole and mosapiride, and patients in the observation group were given MBCT therapy in addition to the above drugs. After treatment for 8 weeks, the changes in gastrointestinal symptom scores, anxiety, depression, mindfulness and sleep quality and gastric emptying testing were compared between these two groups.
RESULTS
The observation group showed strikingly lower gastrointestinal symptom scores, SAS, SDS, PSQI, and SCL-90 scale scores, and higher FFMQ scale scores than the control group ( < 0.05). There was no conspicuous change in gastric emptying monitoring ( > 0.05).
CONCLUSIONS
MBCT therapy can improve patients' gastrointestinal symptoms, attenuate their anxiety and depression levels, and ameliorate their sleep quality.
PubMed: 38888544
DOI: 10.1080/00365521.2024.2368250 -
Journal of Minimally Invasive Surgery Jun 2024Postoperative pancreatic fistula (POPF) remains a devastating complication of pancreatoduodenectomy (PD). Minimally invasive PD (MIPD), including laparoscopic (LPD) and...
PURPOSE
Postoperative pancreatic fistula (POPF) remains a devastating complication of pancreatoduodenectomy (PD). Minimally invasive PD (MIPD), including laparoscopic (LPD) and robotic (RPD) approaches, have comparable POPF rates to open PD (OPD). However, we hypothesize that the likelihood of having a more severe POPF, as defined as clinically relevant POPF (CR-POPF), would be higher in an MIPD relative to OPD.
METHODS
The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted pancreatectomy dataset (2014-2020) was reviewed for any POPF after OPD. Propensity score matching (PSM) compared MIPD to OPD, and then RPD to LPD.
RESULTS
Among 3,083 patients who developed a POPF, 2,843 (92.2%) underwent OPD and 240 (7.8%) MIPD; of these, 25.0% were LPD (n = 60) and 75.0% RPD (n = 180). Grade B POPF was observed in 45.4% (n = 1,400), and grade C in 6.0% (n = 185). After PSM, MIPD patients had higher rates of CR-POPF (47.3% OPD vs. 54.4% MIPD, = 0.037), as well as higher reoperation (9.1% vs. 15.3%, = 0.006), delayed gastric emptying (29.2% vs. 35.8%, = 0.041), and readmission rates (28.2% vs. 35.1%, = 0.032). However, CR-POPF rates were comparable between LPD and RPD (56.8% vs. 49.3%, = 0.408).
CONCLUSION
The impact of POPF is more clinically pronounced after MIPD than OPD with a more complex postoperative course. The difference appears to be attributed to the minimally invasive environment itself as no difference was noted between LPD and RPD. A clear biological explanation of this clinical observation remains missing. Further studies are warranted.
PubMed: 38887001
DOI: 10.7602/jmis.2024.27.2.95 -
Neurogastroenterology and Motility Jun 2024Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical... (Review)
Review
BACKGROUND
Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades.
PURPOSE
The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.
PubMed: 38884392
DOI: 10.1111/nmo.14849 -
Expert Opinion on Drug Metabolism &... Jun 2024Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). (Review)
Review
INTRODUCTION
Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).
AREAS COVERED
Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.
EXPERT OPINION
Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed. The classical D-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT-RA, dexamethasone and a NK-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.
Topics: Humans; Nausea; Vomiting; Antiemetics; Antineoplastic Agents; Dopamine Antagonists; Animals; Dopamine D2 Receptor Antagonists; Receptors, Dopamine D3
PubMed: 38878283
DOI: 10.1080/17425255.2024.2367593 -
Digestive Diseases and Sciences Jun 2024Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with...
UNLABELLED
Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.
AIMS
To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.
METHODS
25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography.
RESULTS
Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01).
CONCLUSIONS
Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.
PubMed: 38877334
DOI: 10.1007/s10620-024-08520-8 -
Neurogastroenterology and Motility Jun 2024Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype...
Low-intensity pulsed ultrasound combined with ST36 modulate gastric smooth muscle contractile marker expression via RhoA/Rock and MALAT1/miR-449a/DLL1 signaling in diabetic rats.
BACKGROUND
Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype was related to the diabetes-induced gastric dysfunction, but the mechanism is not clearly elucidated. This study was aimed at exploring the underlying mechanism of LIPUS stimulation application in diabetic gastroparesis rats.
METHODS
In this study, Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DGP), and LIPUS-treated group (LIPUS). LIPUS irradiation was performed bilaterally at ST36 for 20 min per day for 4 weeks. The gastric emptying rate was measured by ultrasound examination. Contraction ability of GSMCs was assessed by muscle strip experiment. The expression of related proteins or mRNAs including α-SMA, SM22α, MHC, RhoA, Rock2, p-MYPT1, MYPT1, p-MLC, MLC, MALAT1, miR-449a, and DLL1 was detected by different methods such as western blotting, RT-qPCR, immunohistochemistry, and immunofluorescence staining, as appropriate.
KEY RESULTS
(a) LIPUS stimulation at ST36 could improve the gastric motility dysfunction of diabetic rats. (b) LIPUS increased RhoA, Rock2, p-MYPT1, and p-MLC expression level. (c) MALAT1 and DLL1 contents were decreased, but the level of miR-449a was increased in the LIPUS group.
CONCLUSIONS & INFERENCES
LIPUS may affect the contractile marker expression of gastric smooth muscle through the RhoA/Rock and MALAT1/miR-449a/DLL1 pathway to ameliorate DGP.
PubMed: 38873849
DOI: 10.1111/nmo.14843