Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS).

BACKGROUND: Cholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP). METHODS: This prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up. RESULTS: After screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life. CONCLUSION: EUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study.

Some patients develop acute inflammation of the pancreas without a clear cause. These patients have a high risk of developing more episodes of acute inflammation of the pancreas. Potentially, such inflammation could be caused by tiny gallstones that physicians are not able to detect. If this is true, these patients may also benefit from surgical removal of the gallbladder. However, this is still controversial. Endoscopic ultrasonography is a diagnostic procedure during which a physician looks at the gallbladder and bile ducts in detail via a small ultrasound probe inserted through the mouth. This endoscopic ultrasonography may be able to detect gallstones better than physicians were able to previously. This study tested the value of endoscopic ultrasonography, and the number of patients who developed more episodes of acute inflammation after endoscopic ultrasonography was recorded. Some 106 patients with acute inflammation of the pancreas for the first time without a clear cause participated and were offered endoscopic ultrasonography. The number of times endoscopic ultrasonography found a cause for the acute inflammation was recorded, as well as safety parameters, number of patients who developed more episodes of acute inflammation, and quality of life. After screening 957 patients, 105 ultimately underwent endoscopic ultrasonography. A cause was found in one-third of patients. This was mostly (tiny) gallstones, but chronic inflammation and even tumours were found. These patients were mostly treated surgically for their gallstones and tumours. In the first year after the first acute episode of inflammation, the inflammation came back at least once in almost one in six patients in whom endoscopic ultrasonography did not find a cause. This occurred less in patients in whom a cause was found; the inflammation came back in 1 in 16 of these patients. It was also found that having inflammation coming back negatively affected quality of life. In this study, endoscopic ultrasonography was able to detect a cause in one-third of patients with first-time acute inflammation of the pancreas. In one in four patients, this cause could be treated by a surgical procedure. Whether surgical removal of the gallbladder can be helpful in patients in whom endoscopic ultrasonography is not able to detect an aetiology should be investigated in further studies.

18F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC).

Importance: The optimal staging for gastric cancer remains a matter of debate. Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.

Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

BACKGROUND: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff. METHODS: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions. RESULTS: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10). CONCLUSION: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study.

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered.

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Background and study aims The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P  = 0.56) or Cell block (62 % (39/63), P  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P  = 0.02) or Cell block samples (40 % (25/63), P  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70, P  = 0.98), but lower for ThinPrep (ĸ = 0.26, P  = 0.01) than smears. Conclusion After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.

Efficacy of Lactobacillus casei Shirota for patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Meta-analyses point to a modest but significant effect of probiotics on symptoms in irritable bowel syndrome (IBS). We aimed to assess the effect of the probiotic Lactobacillus casei Shirota (LcS) on symptoms and quality of life in IBS patients in a randomized, double-blind, placebo-controlled intervention study. MATERIALS AND METHODS: IBS patients (Rome II) between 18 and 65 years of age were included. The study consisted of an 8-week intervention period in which the participants received probiotic (LcS) or placebo twice daily, followed by an 8-week follow-up period. Symptom diaries and quality of life were scored at weeks 0, 8 and 16. The primary outcome parameter was a decrease of at least 30% in a composite mean symptom score (MSS) at week 8 on the basis of an intention-to-treat analysis. RESULTS: Thirty-nine individuals (67% women) were included in the probiotic group and 41 individuals (71% women) were included in the placebo group. After the intervention period, the mean relative improvement did not reach 30% for MSS or any individual symptom score. After follow-up (week 16), a mean improvement of at least 30% was achieved for MSS in the probiotic group, but no significant difference was found between both treatment groups (mean±SD: 34±7%; 13±8%, P=0.06). CONCLUSION: After probiotic treatment with LcS, no improvement of 30% in MSS was observed after 8 weeks.

[A man with a skin lesion on his abdomen]. / Een man met een huidafwijking op zijn buik.

A 56-year-old man presented with a skin lesion 2 days after surgery for a perianal abscess. The lesion was red, swollen and very painful, with central necrosis and arose shortly after starting coumarine therapy.

Symptoms in patients with ulcerative colitis in remission are associated with visceral hypersensitivity and mast cell activity.

OBJECTIVE: Patients with ulcerative colitis in remission (UCR) frequently report irritable bowel syndrome (IBS)-like symptoms. Recent studies have pointed to the role of mast cells in mediating visceral hypersensitivity in IBS. We hypothesized that visceral hypersensitivity is frequently present in patients with UCR and is related to the quantity and activity of mast cells in the sigmoid mucosa. MATERIAL AND METHODS: A group of 17 controls and 19 patients with UCR were studied. Rectal compliance and perception were measured by electronic barostat. Sigmoid biopsies were taken to quantify the amount of mast cells, degranulating mast cells and mast cells in close proximity to mucosal nerve endings. RESULTS: Visceroperception significantly increased in UCR (p < 0.05) versus controls. Rectal perception correlated positively with IBS-like symptoms in UCR (r = 0.969; p < 0.05). The amount of mucosal mast cells (per 100 crypts) was significantly increased in UCR versus controls: 228 ± 20 versus 163 ± 18 (p < 0.05). In the UCR patients a higher percentage of mucosal mast cells was in close proximity to nerve endings (58 ± 4 vs. 38 ± 3% in controls; p < 0.05) or was degranulating (40 ± 7 vs. 16 ± 4% in controls; p < 0.05). There was a significant but weak correlation between quantity of mucosal mast cells and pain perception (r = 0.32; p < 0.05). CONCLUSION: Rectal hypersensitivity is associated with mucosal presence and activation of mast cells and with IBS-like symptoms in patients with UCR.

Dysfunctional cognitions, anxiety and depression in irritable bowel syndrome.

GOALS AND BACKGROUND: Patients with irritable bowel syndrome (IBS) have significantly impaired quality of life (QoL). We investigated the presence of dysfunctional cognitions, anxiety, and depression symptoms and their impact on daily symptoms and QoL in a large IBS cohort. STUDY: A total of 268 IBS patients (Rome II criteria, age 18 to 65 y) were included. Patients completed a 2-week daily symptom diary. The Short Form-36 was used to score QoL. The 31-items Cognitive Scale for Functional Bowel Disorders (CSFBD) and the Hospital Anxiety and Depression Scale (HADS) were used to analyze the psychological factors. RESULTS: Possible anxiety and depression disorders were present in 30% and 22% of IBS patients, respectively. Patients with anxiety and depression had significantly higher mean symptom scores, impaired QoL, and higher CSFBD scores (P<0.01). Physical and mental QoL were both affected by depression (HADS-D) and dysfunctional cognitions (P<0.01). Only physical QoL, not mental QoL, was affected by referral type (hospital setting vs. community based; P<0.01). Only mental QoL was affected by anxiety (HADS-A) (P<0.01). Dysfunctional cognitions independently of anxiety and depression influenced QoL and IBS symptoms. CONCLUSIONS: In this IBS cohort, dysfunctional cognitions independently influence physical and mental QoL and symptom severity. Presence of possible anxiety and depression disorders resulted in higher symptoms, lower QoL, and higher CSFBD scores. The results point toward an important role of psychological factors, especially dysfunctional cognitions on QoL and symptom scores in IBS patients.