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Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation., Significance: This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Grouping of patients based on a predominant dyspeptic symptom is frequently employed in management strategies for dyspepsia. Such subdivision, however, suggests that dyspeptic symptom patterns are constant over time., Objective: To investigate the behavior of symptoms over time and to study the effects of diagnostic procedures and treatment on the pattern and severity of dyspeptic symptoms., Methods: Patients with persistent dyspeptic symptoms completed a validated questionnaire at regular time intervals as part of a clinical trial in primary care. Based on predominant symptoms, patients were classified into ulcer-like dyspepsia, reflux-like dyspepsia, dysmotility-like dyspepsia, and unspecific dyspepsia according to the Rome II criteria., Results: Questionnaires were returned at baseline, 1, 3, and 6 months by 185, 172, 169, and 170 patients, respectively. At baseline, 35% of patients reported predominantly reflux-like dyspepsia, 34% had ulcer-like dyspepsia, 16% had dysmotility-like dyspepsia, and in 15% symptoms were not specific. During the 6-month follow-up period, only 35% of patients kept the same predominant symptom. Symptom (in)stability was not dependent on diagnostic procedures or on therapy with proton pump inhibitors, H2-receptor antagonists, prokinetics, or antacids., Conclusion: In the majority of dyspeptic patients, symptoms change continuously as time goes on. Symptom instability is not influenced by diagnostic procedures or therapy. Thus, there is little sense in symptom-based management of dyspepsia in primary care.

Helicobacter pylori serology and in particular enzyme-linked immunosorbent assays for the measurement of immunoglobulin G (IgG) antibody titers form an accurate means of diagnosing H. pylori infection in patients before treatment. H. pylori serology is of limited value in monitoring treatment because of the slow decline in antibody titers. In the present study we aimed to measure the most suitable moment after antibiotic treatment at which serology should be used to monitor treatment. Sixty-four patients who had nonulcer dyspepsia and H. pylori infection and who underwent upper gastrointestinal endoscopy because of persistent dyspeptic symptoms were included in the study. H. pylori cure was confirmed by histology and culture 5 weeks after the completion of the antibiotic treatment. Serological examination was performed before therapy and at 5 weeks, 10 weeks, and 1 year after the completion of antibiotic treatment. Diagnostic performance was assessed by receiver-operating characteristic analysis. The areas under the receiver-operating characteristic curves of the H. pylori antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment were 0.53 (95% confidence interval [CI], 0.36 to 0.69), 0.60 (95% CI, 0.43 to 0.76), and 0.78 (95% CI, 0.63 to 0.93), respectively. The areas under the receiver-operating characteristic curves of the changes in H. pylori IgG antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment in comparison with the pretreatment titers were 0.85 (95% CI, 0.72 to 0.97), 0.96 (95% CI, 0.89 to 1.0), and 1.0 (95% CI, not estimable), respectively. We conclude that serology forms a useful means of monitoring treatment in patients with nonulcer dyspepsia and H. pylori infection as early as 10 weeks and maybe even sooner after the completion of treatment for the infection.

A large hepatocellular adenoma was diagnosed in a female patient who was referred for severe upper abdominal pain. She had been using oral contraceptives over a period of 14 years. The clinical features, diagnosis and treatment are discussed.

Aims: To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system., Methods: Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis., Results: The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage., Conclusion: Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.

Background: Helicobacter pylori infection of the antral mucosa is responsible for an increase in basal and stimulated serum gastrin. In the present study we have investigated whether gastritis induced by H. pylori is responsible for abnormalities in the processing of gastrin in dyspeptic patients., Methods: Basal serum gastrin was measured by radioimmunoassay before, 5 weeks, and 1 year after anti-H. pylori therapy in 73 H. pylori positive functional dyspeptic patients. Three region-specific antisera were used, specific for the biologically active carboxy-terminal part, the biologically inactive amino-terminal part of gastrin 1-17, and for the non-sulphated tyrosyl residue in gastrin 1-17., Results: Basal serum gastrin levels were markedly (P < 0.01) decreased 5 weeks and 1 year after successful eradication of H. pylori (n = 39) but not in the patients in whom treatment failed (n = 34). A decline of gastrin was observed for each of the three radioimmunoassays., Conclusion: The decrease of serum gastrin levels in all three radioimmunoassays after a successful eradication of H. pylori does not point to major changes in the processing of gastrin. These results suggest that G-cells in the antral mucosa are not functionally affected by the inflammation.

Thirty-three dyspeptic patients with colonization of Helicobacter pylori in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s. for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.

A young male patient was referred for endoscopic resection of a recto-sigmoid polyp and abdominal complaints. His medical history revealed a sebaceous adenoma resection from his back and a tubular adenoma excision from his right upper eyelid. After disclosure of a jejunal tumour on a small bowel enema and given the remarkable family history characterized by the frequent occurrence of bowel cancer, the diagnosis of Muir-Torre syndrome was established. This syndrome pertains to the combination of sebaceous gland tumours/adenomas in combination with gastrointestinal or genitourinary tract tumours. Inheritance takes place in an autosomal dominant manner. It usually occurs in males at an early age. Given its low malignancy potential, early detection of the syndrome renders a favourable prognosis. Careful examination and follow-up also involving the small intestine are mandatory for patients and relatives.

A patient known with acute intermittent porphyria who developed primary liver-cell carcinoma is described. No other risk factors were found. A possible association of acute intermittent porphyria with the development of primary liver-cell carcinoma has been suggested in recent, mainly Scandinavian literature. So far this association has never been described in The Netherlands.

During 1968-1988 one endoscopist performed 3154 endoscopic examinations of the upper gastrointestinal tract and detected 400 (13%) malignancies. Endoscopy was indicated in persisting dyspepsia or abnormal findings on X-ray examination of the stomach. In 242 patients earlier subjected to partial gastrectomy 7% stomach cancers were found. No difference existed in the incidence of stomach cancer between patients with either BI and BII gastrectomy. Initially no malignancy was detected in 9 (2.3%) patients. The maximum diagnostic delay was 5 months in these patients. This finding underlines the necessity of a strict follow-up scheme when studying malignancies.

Detection of liver cell membrane autoantibodies is routinely performed by immunofluorescence testing of patient sera on rabbit hepatocyte suspensions. We have investigated the possible use of cells from the PLC/PRF/5 human hepatoma cell-line. These cells were employed as substrate in an immunofluorescence test which was compared with the conventional rabbit hepatocyte assay. We found a close correlation between the results obtained with these different substrates on visual reading. We furthermore compared visual reading of immunofluorescence preparations with flow-cytometrical analysis of immunostained cell suspensions. The results with these different methods were largely confirmatory. The PLC/PRF/5 cells are easily available and should therefore be regarded as a highly valuable new substrate for detection of liver cell membrane autoantibodies. Flow cytometry appears to be a technically simple and reliable method for quantitative analysis.

We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co-capping. The presence of a "division" antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.

Chronic pancreatitis, often with a pseudocyst, is a rare cause of a pleural exudate. A pancreatic pleural fistula is created, leading to a relapsing massive haemorrhagic pleural exudate with a very high amylase content. The diagnosis is confirmed by means of endoscopic retrograde pancreatography. Treatment is primarily conservative; surgical drainage is sometimes necessary. The prognosis is generally favourable. The case history of a young woman with this condition is presented.