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At least 19 recordsLinked to original sources

Proton penetration and control in nonhomogeneous phantoms.

Accurate bolus is needed for extension of Bragg-peak therapy. Proton beam-stopping profiles in a lucite-styrofoam-tissue phantom and in a Rando phantom were recorded photographically. Air volumes caused the largest distortions. Lucite bolus was cut to achieve desired beam-stopping profiles. Verification of bolus effect in situ will be important to control beam penetration within 5 mm.

Models, Structural

Efficacy of Proton Pump Inhibitor Therapy for Nocturnal GERD Symptoms and Associated Sleep Disturbances: A Systematic Review of Randomized Controlled Trials.

GOALS: A systematic review was conducted to evaluate the efficacy and safety of proton pump inhibitor (PPI) therapy in relieving nocturnal reflux symptoms and sleep disturbances. BACKGROUND: Nocturnal gastroesophageal reflux disease (GERD) is commonly associated with sleep disturbances. The benefits of PPI therapy for GERD-related nocturnal reflux and sleep disturbance remain unclear. STUDY: We searched the MEDLINE, EMBASE, and Cochrane CENTRAL databases from inception to March 1, 2026, for randomized controlled trials (RCTs) in adults with GERD and sleep disturbances that compared any PPI to placebo or an alternative therapy. The primary outcome was the proportion of patients experiencing relief from nighttime heartburn. Secondary outcomes included relief from GERD-related sleep disturbances, changes in subjective sleep quality, work productivity, and treatment-emergent adverse events (TEAEs). RESULTS: Five RCTs involving 1495 patients met the inclusion criteria. Three placebo-controlled trials consistently showed that PPI therapy improved nighttime heartburn relief and GERD-related sleep disturbances compared with placebo. Subjective sleep quality and sleep-related daytime functioning also generally improved with PPI therapy. However, the findings were more heterogeneous across trials because of differences in study populations, comparators, and outcome measures. Across the placebo-controlled studies, TEAEs were generally similar between the PPI and placebo groups. CONCLUSIONS: PPI therapy was associated with improvement in nighttime heartburn and reflux-related sleep disturbances, especially in patients with reflux-driven nocturnal symptoms. The available evidence also suggests potential improvement in subjective sleep quality and sleep-related daytime functioning.

Humans

Proton radiation as boost therapy for localized prostatic carcinoma.

A 160-MeV proton beam has been modified to irradiate patients with localized tumors by using convention treatment schedules. This proton beam has the physical advantage of megavoltage x-rays of reducing the radiation dose to normal tissues adjacent to the tumor volume. A perineal proton technique used as boost therapy (2,000 to 2,500 rads) was evaluated in the definitive irradiation of 17 patients with localized prostatic carcinoma. This technique allows repeated daily treatment of the carefully defined target volume with a precision of +/- 2 mm. Total dose to the prostatic tumor, but not to the posterior rectum, has been increased by 500 to 700 rads. After 12 to 27 months of observation, no noteworthy rectal reaction has developed in a patient, easily managed urethral strictures have developed in two patients, and all but one are locally controlled.

Adenocarcinoma

The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans

Quantitative analysis of the pituitary fossa and gland in Cushing's disease.

With tomography and encephalography of 78 cases with primary Cushing's disease, changes in the appearance of the pituitary gland and fossa have been demonstrated in greater numbers than previously reported. One or more direct or indirect signs of enlargement of the pituitary gland either by hyperplasia, microadenoma, or adenoma occurred in 60 per cent. Most of these cases were unproved as to cell type because they were given proton beam therapy. There were more cases of pituitary enlargement in those with adrenalectomy in comparison to non-adrenalectomy cases and in those with pigmentation in comparison to non-pigmented cases. The high incidence of pituitary gland enlargement in the different phases of this disease supports the importance of this gland in the pathogenesis of primary Cushing's disease. Limitation in correlation of the pituitary fossa to size of the pituitary gland when the latter enlarges only slightly has been discussed.

Adenoma, Chromophobe

Role of the parietal cell in gastric damage induced by aspirin and related drugs: implications for safer therapy.

The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs.

Animals

Neutron spectra from deuteron and proton bombardment of thick lithium targets: potential for neutron therapy.

Neutron energy spectra and yields produced by the bombardment of thick lithium targets by deuterons and protons have been measured using the time-of-flight method. Measurements were made at angles up to 45 degrees for deuteron energies of 8, 12 and 15 MeV and a proton energy of 15 MeV. The average neutron energy of the (d, n) reactions is shown to vary approximately as 0.44Ed. The (p, n) reaction has En = 4.7 MeV. The tissue penetration of neutron therapy beams is dependent on their average neutron energy and thus the low average neutron energy for these reactions appears to preclude their use for practical neutron therapy at these incident particle energies.

Deuterium

Fourteen-Day Amoxicillin- or Tetracycline-Containing Bismuth Quadruple Therapy versus 14-Day Metronidazole-Based Triple Therapy as the Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial.

BACKGROUND/AIMS: Combination therapy comprising a proton pump inhibitor (PPI), amoxicillin, and metronidazole (PAM) is used to treat clarithromycin-resistant Helicobacter pylori in the Republic of Korea, but eradication rates are decreasing due to an increasing incidence of clarithromycin resistance. We compared PAM, bismuth compounds plus PAM (PAM-B), and the combination of PPI, bismuth compounds, metronidazole, and tetracycline (PBMT) to determine whether PAM-B can achieve an eradication rate higher than that of PAM and comparable to that of PBMT. METHODS: This prospective multicenter study enrolled patients with clarithromycin-resistant H. pylori infections in the Busan and Gyeongsangnam-do of the Republic of Korea between December 2022 and February 2024. RESULTS: In the intention-to-treat (ITT) analysis, the eradication rate was significantly lower in the PAM group (68.2%) than in the PAM-B group (84.8%, p=0.024), whereas the difference from the PBMT group (81.8%) was not significant (p=0.070). The rate remained lowest in the PAM group (75.4%) in the per-protocol (PP) analysis (PAM-B, 96.5%, p=0.001; PBMT, 94.6%, p=0.004). Eradication rates were comparable between the PAM-B and PBMT groups in both the ITT (p=0.640) and PP analyses (p=0.633). Nausea and vomiting were significantly less frequent in the PAM-B group than in the PBMT group (6.8% vs 25.0%; p=0.007). Severe adverse events were rare, and all symptoms resolved after treatment discontinuation. CONCLUSIONS: PAM-B yielded eradication rates higher than those of PAM and comparable to those of PBMT, with no significant increase in the incidence of adverse events, suggesting the potential of PAM-B as a first-line treatment for clarithromycin-resistant H. pylori infection. Further large-scale studies are needed to validate these results. Registered retrospectively with the Clinical Research Information Service (CRIS; KCT0012265).

Humans

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ&#x2265;8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p&#x202f;<&#x202f;0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p&#x202f;<&#x202f;0.01), and TCM syndrome score (69.23% vs 30.13%, p&#x202f;<&#x202f;0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d) or 14-day of EA therapy (Esomeprazole 40&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p&#x2009;=&#x2009;0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p&#x2009;=&#x2009;0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p&#x2009;=&#x2009;0.155). Non-inferiority was confirmed between the two groups (all p&#x2009;<&#x2009;0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans

Recent advances in radiotherapy.

Significant recent achievement in radiotherapy are presented, with brief discussions of brachytherapy, clinical dose-rate effects, ultrafractionation, and total and half-body irradiation. Reports on radiation modifiers, including hyperbaric oxygen, chemical radiosensitizers, and normal tissue protective agents are briefly summarized, while the potential of local and systemic hyperthermia is discussed in greater detail. Recent reports of local tumor control in so-called "radioresistant tumors," such as salivary gland tumors, adenocarcinomas of the breast, prostate and pancreas, malignant melanoma and malignant carcinoid, are summarized. Current status of heavy particle radiotherapy is discussed in detail. Results of initial clinical trials of neutron beam therapy are summarized, and a brief review of proton beam clinical trials and pion beam facilities is included. Recent reports defining the role of combined irradiation and surgery in rectal and breast cancer, and in soft tissue sarcomas, are discussed. Reports of enhanced radiation toxicity seen with concomitant or sequential chemotherapy and radiotherapy are detailed, including CNS toxicity seen with methotrexate and cytosine arabinoside, cardiotoxicity with adriamycin, and pulmonary toxicity with bleomycin. New or improved diagnostic techniques with special relevance to radiotherapy treatment planning, including CT scanning, histerography, internal mammary lymphoscintigraphy, and upper extremity lymphangiography are described.

Breast Neoplasms

High-energy protons in the postoperative treatment of malignant glioma.

Fractionated irradiation with high-energy protons was given postoperatively to seven patients with malignant glioma. In four cases in which detailed microscopic examinations were performed, radiation induced tumour necrosis was evident but in all four cases viable tumour cells were also observed. No abnormalities that could be attributed to radiation were observed in brain tissue free from tumour. The therapeutic results were comparable to the results achieved by other modern therapies. The results support the view that the RBE of high-energy protons is similar to that for 60Co radiation. It is suggested that a larger radiation dose, delivered by a homogeneous, well-defined proton field could possibly result in an improved therapeutic result without undue risk of injury to normal brain tissue.

Adult

Marked response to dabrafenib plus trametinib in a patient with BRAF V600E-mutant pancreatic hepatoid carcinoma: a case report and systematic analysis of 57 cases.

BACKGROUND: Pancreatic hepatoid carcinoma (PHC) is an extremely rare pancreatic malignancy characterized pathologically by hepatocellular-like differentiation. Some patients may present with elevated serum alpha-fetoprotein (AFP). Owing to the limited number of reported cases, the clinical features, molecular characteristics, and systemic treatment strategies for PHC remain poorly defined. BRAF V600E is an actionable alteration with established therapeutic value in several solid tumors; however, its clinical significance in PHC remains unclear. CASE PRESENTATION: We report the case of a 64-year-old man with advanced PHC who presented with painless jaundice, dark urine, and recent weight loss. Laboratory tests showed marked cholestatic liver injury and significantly elevated AFP. Imaging revealed a pancreatic head-neck mass with portal vein tumor thrombus and regional lymph node metastases, corresponding to cT4N1M1, stage IV disease. Percutaneous transhepatic biliary drainage was first performed to relieve obstructive jaundice. Biopsy of the pancreatic lesion showed poorly differentiated carcinoma. Based on hepatoid morphology, immunophenotype, elevated serum AFP, imaging findings, and exclusion of primary hepatocellular carcinoma, the patient was diagnosed with PHC. Comprehensive genomic profiling identified a BRAF V600E mutation with a variant allele frequency of 31.89%, together with MDM2 and MYC amplification. The molecular profile was characterized by microsatellite stability, low tumor mutational burden, MGMT promoter methylation, and low PD-L1 expression. After two cycles of pembrolizumab-based first-line therapy combined with paclitaxel, S-1, and lenvatinib, AFP continued to increase and imaging showed rapid tumor enlargement, consistent with immune checkpoint inhibitor-related hyperprogressive disease. The treatment was then switched to dabrafenib plus trametinib. AFP declined rapidly and returned to the normal range within approximately two months. Imaging showed marked regression of the pancreatic primary lesion, disappearance of the portal vein tumor thrombus and metastatic lymph nodes, and conversion of peripheral blood minimal residual disease to negative. The best response was partial response. After approximately six months of targeted therapy, occult disease progression emerged. Subsequent addition of cetuximab, replacement of the MEK inhibitor, and dose escalation of targeted therapy did not restore sustained systemic disease control, although local disease remained manageable with subsequent treatment adjustments. Proton radiotherapy was then delivered to the residual pancreatic lesion, followed by CyberKnife radiotherapy for a newly detected 2.3-cm metastasis in the caudate lobe of the liver. As of April 2026, the patient's AFP level remained close to normal at 14 ng/mL, local lesions were well controlled, peripheral blood minimal residual disease had turned positive, and the patient remained in a stable tumor-bearing state. SYSTEMATIC ANALYSIS: We further summarized 57 previously reported cases of PHC. The median age was 54 years, and 66.7% of patients were male. Tumors occurred at different pancreatic sites, including the pancreatic head in 21 cases, body in 8 cases, tail in 13 cases, and multifocal lesions in 15 cases. More than half of the patients had metastatic disease at initial diagnosis. The immunophenotype of PHC was highly heterogeneous. Regarding treatment, 47 patients underwent surgery, 20 received chemotherapy, and 6 received targeted therapy. The 1-year and 3-year overall survival rates were 70.7% and 43.1%, respectively, indicating an overall poor prognosis. CONCLUSION: This case suggests that BRAF V600E may represent a clinically actionable driver alteration in PHC. Dabrafenib plus trametinib induced a rapid and deep response in this patient with advanced BRAF V600E-mutant PHC. Microsatellite stability, low tumor mutational burden, low PD-L1 expression, and MDM2 amplification may be associated with limited benefit from immunotherapy and a risk of hyperprogression. After resistance to targeted therapy, local radiotherapy may serve as an important strategy for controlling oligoresidual and oligometastatic lesions. Together with the literature review, this case supports early comprehensive molecular profiling and individualized multidisciplinary management for advanced PHC.

BRAF V600E

Multiple choroidal metastasis from bronchial carcinoid treated with photocoagulation and proton beam irradiation.

A 23-year-old man had bilateral multiple choroidal lesions eight years after removal of a bronchial carcinoid tumor. Choroidal biopsy confirmed that the clinical diagnosis and conventional radiotherapy to one eye resulted in rubeosis iridis, neovascular glaucoma, cataract, and vitreous hemorrhage. We were able to destroy the tumors in the other eye by photocoagulation and proton beam irradiation without any adverse effects. The patient is in good health 1 1/2 years after therapy and he has 6/6 (20/20) vision in the eye that was treated.

Adult