MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC).

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.

Crohn's disease: A retrospective analysis between computed tomography enterography, colonoscopy, and histopathology.

INTRODUCTION: To investigate the spectrum of computed tomography enterography (CTE) findings of active Crohn's disease (CD) in comparison to endoscopic, histopathologic and inflammatory markers. METHODS: Hospital records of 197 patients with known or suspected CD who underwent CTE over a period of 5 years were reviewed. Eighty-nine patients fulfilled the inclusion criteria. Three-point severity scores for endoscopy, pathology, and haematologic inflammatory markers were recorded. The findings on CTE were identified by three readers and correlated with endoscopic, pathologic, and haematologic severity scores. Statistical analysis was carried out employing a Pearson Chi square test and Fisher exact test. Receiver operating characteristic (ROC), visual grading characteristic (VGC) and Cohens' kappa analyses were performed. RESULTS: The CTE findings which were significantly correlated with the severity of active disease on endoscopy include bowel wall thickening, mucosal hyperenhancement, bilaminar stratified wall enhancement, transmural wall enhancement, and mesenteric fluid adjacent to diseased bowel (p < 0.05). Only bowel wall thickening and bilaminar stratified wall enhancement correlated with the pathological severity of active CD. ROC and VGC analysis demonstrated significantly higher areas under the curve (p < 0.0001) together with excellent inter-reader agreement (k = 0.86). CONCLUSION: CTE is a reliable tool for evaluating the severity of active disease and helps in the clinical decision pathway.

Does living in crowded houses offer protection against the development of inflammatory bowel disease?

INTRODUCTION: The credibility of the "Hygiene hypothesis" in patients with inflammatory bowel disease has been assessed. OBJECTIVE: This survey is aimed at finding an answer for the question: "Does living in crowded or overcrowded houses protect against the development of inflammatory bowel disease?" PATIENTS AND METHODS: Asian immigrants to the United Kingdom who attended inflammatory bowel diseases' clinics during the period of the study and who fulfilled Leonard-Jones criteria were asked to complete a questionnaire. The participants were asked to respond to questions on age, sex, their birth rank, diagnosis, & number of brothers, sisters, sons and daughters. RESULTS: 60% of the participants had four or more brothers and sisters. Forty per cent of the participants grew in crowded houses (occupied the fourth birth rank). CONCLUSIONS: Our presented data do not support any role of the number of house inhabitants in the development of inflammatory bowel disease.

A preliminary investigation of Beta-hCG expression in patients with osteosarcoma.

There are eight reported cases in the literature of osteosarcomas secreting ß-hCG. Our primary aim was to investigate the rate of ß-hCG expression in osteosarcoma and attempt to understand the characteristics of osteosarcomas that secrete ß-hCG. We reviewed 37 histopathology slides (14 biopsies and 23 surgical specimens) from 32 patients with osteosarcoma. The slides were retrospectively stained for ß-hCG expression. Patient and tumour characteristics, including age, gender, tumour location, subtype, proportion of necrosis, presence of metastases and recurrence were recorded. A total of five of the 32 tumours were found to be positive for ß-hCG expression (one strongly and four weakly). This incidence of this expression was found in tumours with poor histological response to neoadjuvant chemotherapy. The use of ß-hCG expression as a diagnostic, prognostic or follow-up marker is questionable and needs further investigation with a larger sample size.

Mechanism of non-specific-fistula-in-ano: Hormonal aspects-Review.

Abscesses could occur anywhere, but quite few that could proceed forward and develop fistulae. Crypto glandular abscess formation concept has been forming the basis for almost all designed strategies for management of cases of idiopathic fistula-in-ano for ages. Yet, this hypothesis failed to explain the reason(s) for the recorded lower incidences of idiopathic anal fistula in females than in males. Gram negative bacteria are largely the causative agents for these anal glands' abscesses that processed further and developed fistulae. Lipopolysaccharide component (LPS) of the bacterial cell wall could significantly attenuate the expression of mRNA of the oestrogen receptors and accordingly reduces the down signalling pathway. Yet, this kind of action could be inhibited in the presence of oestrogen. In addition, tumour necrosis factor-alpha (TNFα) is a key proinflammatory cytokine that induces the secretion of other cytokines and enzymes in various cells and tissues. And LPS could activate pro-inflammatory cytokine by activating plasma membrane proteins (e.g. the toll like receptor 4 [TLR4] and CD14 that leads to the production of TNFα and other pro-inflammatory cytokines). This activation could be enhanced by testosterone but inhibited by oestrogen. These are likely the reasons for the higher prevalence of idiopathic fistula-in-ano in males than in females.

High carbohydrates consumption and inflammatory bowel diseases.

High consumption of potatoes, soft drinks, cornflakes, chocolates, mushrooms and other common examples of complex carbohydrates in the western side of the globe is significant. Similarly, Inflammatory Bowel Diseases (IBD) (Crohn's disease and ulcerative colitis) are also prevalent in these regions. Evidence exists to support that factors, such as lack of zinc (it is common in patients with IBD, in particular Crohn's patients) may significantly affect the activity of some enzymes, such as, disaccharidases and other digesting enzymes of carbohydrates and that would lead to the recruitment of incompletely digested carbohydrates to the terminal ileum and continual stimulation of the immune-response accordingly. This concept may explain the observation of the existence of higher significant percentage of severe disease in Caucasian patients with IBD comparable with the respected Asian patients who consume less.

Implications of abnormal pathology in fulminating colitis on the outcome of surgery.

BACKGROUND: The severe relapse of the diseases in patients with Crohn's disease or ulcerative colitis is associated with high morbidity and mortality. Early prediction for the failure of aggressive medical treatment and consequently, early surgical interference in cases with severe colitis and severe Crohn's colitis are supposed to be effective means for reducing these high rates. METHODS: Patients who presented at the Accident & Emergency Department with severe colitis and severe Crohn's colitis and on whom emergency colectomy was operated were identified and they formed the basis of this study. RESULTS: Patients (n=34) with acute fulminating colitis and their condition required emergency colectomy were seen over a period of 5 years. A strategy of early detection of cases of toxic dilatation and/or perforation proved efficient in reducing morbidity and mortality in cases of severe colitis. The mortality in the presented series was zero and the morbidity occurred mainly in such cases that presented with fulminant distal colitis, which was complicated by proximal faecal loading. CONCLUSION: Diagnosis of proximal faecal loading in cases with fulminant colitis is likely to be an indication for surgery. Further studies are required for confirming this conclusion.

Colorectal cancer and pollution.

The incidence of colorectal carcinoma is increasing in young patients, in contrast to the well established wisdom that it is exclusively diagnosed in patients older than 40 years. In this survey, we examined all possible risk factors, and we recommend a number of measures for early detection in young patients who are at risk of developing this malignant tumor.

Smoking and inflammatory bowel diseases: what in smoking alters the course?

Epidemiological studies provide strong evidence to confirm the correlation between cigarette smoking and inflammatory bowel diseases. This relationship is proved to be positive in Crohn's disease and negative in ulcerative colitis. What in smoking alters the course of inflammatory bowel diseases is still a mystery. Different smoking parts have different and may be opponent actions. Smoking has dual effects. Some of its activities are, sometimes, constructive as they are working in an antagonistic manner to the mechanism of the disease, such as reducing rectal blood flow and accordingly less recruitments of inflammatory mediators to the area of inflammation, enhancement of mucosal production, and consequently, strengthening the membranes, and inhibition of pro-inflammatory mediators' liberation and activity in subjects with ulcerative colitis. Yet the outcome of smoking actions may be affected by the existence of other cofactors. Odd factors, such as shortage of zinc in subjects with Crohn's disease, may facilitate liberation of pro-inflammatory mediators and their activities and accordingly exacerbates symptoms.

Is the DHEAS/cortisol ratio a potential filter for non-operable constipated cases?

Constipation is a significant manifestation of a number of psychological disorders. Published papers recommend using self-assessment questionnaires for discriminating psychological from non-psychological constipated patients before operating on them but reports from major surveys revealed that general practitioners failed to diagnose 70% of depressed patients using self-assessment questionnaires. Lower circulating concentrations of progesterone, 17-hydroxyprogesterone, cortisol, testosterone, androstenedione, and dehydroepiandrostenedione sulfate (DHEAS) during the follicular phase in constipated young women compared with respective controls were found during the follicular phase of the menstrual cycles. During the luteal phase of the cycle, reductions were identified in estriol, cortisol and testosterone in the constipated group. Likewise, circulating concentrations of DHEAS were found to be lower in depressed patients than comparable healthy controls. DHEAS/cortisol ratios in morning serum and salivary samples were lower than those retrieved during other times of the day in depressed patients. The idea of recognizing major depression in constipated patients by measuring DHEAS/cortisol ratios in saliva and serum may be plausible but this possibility needs to be confirmed in well-designed studies.

Oestrogens and Crohn's disease: the missed link.

Observational studies, sometimes, can not provide us with clear answers for very important questions. The answer for a question on whether sex hormones in general, and oestrogen in particular, play some role in inducing and development of Crohn's disease is uncertain. Study design, inclusion criteria, and different formulations of oral contraceptives may partly explain the conflict results of the published reports. But these may be due to the divergent effects of oestrogen, which are based on dose, tissue specificity and cellular environment. This paper is aimed at examining the influence of androgens on the prognosis of Crohn's disease.

Primary pure squamous cell carcinoma of the breast: a case report and review of the literature.

Pure primary squamous cell carcinoma (SCC) of the breast is a rare condition. The exact histogenesis of this malignancy is unclear. The rarity of the condition makes it difficult to draw firm conclusions on the course of the disease and the overall prognosis. We report a case of pure primary SCC of the breast occurring in a 62-year-old woman and presenting as an enlarged breast lesion with bleeding. We also review the literature for all cases of pure primary SCC.

Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

BACKGROUND: The response rates and duration of peginterferon alpha (PEG-IFN-alpha) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented. AIMS: To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-alpha-2b and ribavirin therapy in chronic hepatitis C genotype 4. METHODS: In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-alpha-2b (1.5 mug/kg) once weekly plus daily ribavirin (1000-1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment. RESULTS: Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-alpha-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (epsilon) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks. CONCLUSION: PEG-IFN-alpha-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.