Intrarectal formalin treatment for haemorrhagic radiation-induced proctopathy: efficacy and safety.

AIM: Pelvic radiotherapy is limited by dose-dependent toxicity to surrounding organs. The aim of this prospective study was to evaluate the efficacy and safety of intrarectal formalin treatment for radiotherapy-induced haemorrhagic proctopathy (RHP) at the Royal Marsden Hospital. METHOD: Adult patients were enrolled. Haemoglobin was evaluated before and after formalin treatment. Antiplatelet and/or anticoagulation treatment and administration of transfusion were recorded. The interval between completion of radiotherapy and the first intrarectal 5% formalin treatment was assessed and the dose of radiotherapy was evaluated. Clinical assessment of the frequency and amount of rectal bleeding (rectal bleeding score 1-6) and endoscopic appearance (grade 0-3) were classified. Complications were recorded. RESULTS: Nineteen patients were enrolled, comprising 13 men (68%) and 6 women. The mean age was 75 ± 9 years. The median time between completion of radiotherapy and the first treatment was 20 months [interquartile range (IQR) 15 months] and the median dose of radiotherapy was 68 Gy (IQR 14 Gy). Thirty-two procedures were performed (average 1.7 per patient). In total, 9/19 (47%) patients were receiving anticoagulation and/or antiplatelet medication and 5/19 (26%) received transfusion prior to treatment. The mean value of serum haemoglobin before the first treatment was 110 ± 18 g/L and afterwards it was 123 ± 16 g/L (p = 0.022). The median rectal bleeding score before the first treatment was 6 (IQR 0) and afterwards 2 (IQR 1-4; p < 0.001), while the median endoscopy score on the day of first treatment was 3 (IQR 0) compared with 1 (IQR 1-2) on the day of the last treatment 1 (p < 0.001). One female patient with a persistent rectal ulcer that eventually healed (18 months of healing) subsequently developed rectovaginal fistula (complication rate 1/19, 5%). CONCLUSIONS: Treatment with intrarectal formalin in RHP is effective and safe.

Diabetes Mellitus in Pancreatic Cancer: A Distinct Approach to Older Subjects with New-Onset Diabetes Mellitus.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis, with near-identical incidence and mortality. According to the World Health Organization Globocan Database, the estimated number of new cases worldwide will rise by 70% between 2020 and 2040. There are no effective screening methods available so far, even for high-risk individuals. The prognosis of PDAC, even at its early stages, is still mostly unsatisfactory. Impaired glucose metabolism is present in about 3/4 of PDAC cases. METHODS: Available literature on pancreatic cancer and diabetes mellitus was reviewed using a PubMed database. Data from a national oncology registry (on PDAC) and information from a registry of healthcare providers (on diabetes mellitus and a number of abdominal ultrasound investigations) were obtained. RESULTS: New-onset diabetes mellitus in subjects older than 60 years should be an incentive for a prompt and detailed investigation to exclude PDAC. Type 2 diabetes mellitus, diabetes mellitus associated with chronic non-malignant diseases of the exocrine pancreas, and PDAC-associated type 3c diabetes mellitus are the most frequent types. Proper differentiation of particular types of new-onset diabetes mellitus is a starting point for a population-based program. An algorithm for subsequent steps of the workup was proposed. CONCLUSIONS: The structured, well-differentiated, and elaborately designed approach to the elderly with a new onset of diabetes mellitus could improve the current situation in diagnostics and subsequent poor outcomes of therapy of PDAC.

Wireless Monitoring of Gastrointestinal Transit Time, Intra-luminal pH, Pressure and Temperature in Experimental Pigs: A Pilot Study.

BACKGROUND: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. AIMS: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. METHODS: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. RESULTS: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5-34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. CONCLUSIONS: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

Escherichia coli from biopsies differ in virulence genes between patients with colorectal neoplasia and healthy controls.

Introduction: Pathogenic strains of Escherichia coli have been clearly identified as the causative agents of extraintestinal and diarrheal infections; however, the etiopathogenic role of E. coli in other conditions, including colorectal cancer, remains unclear. Methods: This study aimed to characterize mucosal E. coli isolates (n = 246) from 61 neoplasia patients and 20 healthy controls for the presence of 35 genetic determinants encoding known virulence factors. Results: Virulence determinants encoding invasin (ibeA), siderophore receptor (iroN), S-fimbriae (sfa), and genotoxin (usp) were more prevalent among E. coli isolated from patients with neoplasia compared to the control group (p < 0.05). In addition, the prevalence of these virulence determinants was increased in more advanced neoplasia stages (p adj < 0.0125). Compared to patients with advanced colorectal adenoma and carcinoma, the ibeA gene was rarely found in the control group and among patients with non-advanced adenoma (p < 0.05), indicating its potential as the advanced-neoplasia biomarker. Patients with neoplasia frequently had E. coli strains with at least one of the abovementioned virulence factors, whereby specific combinations of these virulence factors were found. Discussion: These findings suggest that E. coli strains isolated from patients with colorectal neoplasia possess several virulence factors, which could contribute to the development of neoplastic processes in the large intestine.

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019-January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/- 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective.

Advances in the Aetiology & Endoscopic Detection and Management of Early Gastric Cancer.

The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) - A Helicobacter-opposite point.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare familial gastric cancer syndrome with an autosomal dominant pattern of inheritance. It is characterised by fundic gland polyposis of the gastric body and is associated with a significant risk of gastric adenocarcinoma. Unlike sporadic gastric cancer, Helicobacter pylori is usually absent in patients with GAPPS. This opposite-point finding has so far not been fully clarified. Prophylactic total gastrectomy is indicated in all cases of GAPPS with fundic gland polyposis and the presence of any dysplasia. If no dysplasia is found at histology, prophylactic gastrectomy is suggested at between 30 and 35 years of age, or at five years earlier than the age at which the youngest family member developed gastric cancer. Different phenotypes of GAPPS demand an individual approach to particular family members.

Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

Tissue mRNA for S100A4, S100A6, S100A8, S100A9, S100A11 and S100P Proteins in Colorectal Neoplasia: A Pilot Study.

S100 proteins are involved in the pathogenesis of sporadic colorectal carcinoma through different mechanisms. The aim of our study was to assess tissue mRNA encoding S100 proteins in patients with non-advanced and advanced colorectal adenoma. Mucosal biopsies were taken from the caecum, transverse colon and rectum during diagnostic and/or therapeutic colonoscopy. Another biopsy was obtained from adenomatous tissue in the advanced adenoma group. The tissue mRNA for each S100 protein (S100A4, S100A6, S100A8, S100A9, S100A11 and S100P) was investigated. Eighteen biopsies were obtained from the healthy mucosa in controls and the non-advanced adenoma group (six individuals in each group) and thirty biopsies in the advanced adenoma group (ten patients). Nine biopsies were obtained from advanced adenoma tissue (9/10 patients). Significant differences in mRNA investigated in the healthy mucosa were identified between (1) controls and the advanced adenoma group for S100A6 (p = 0.012), (2) controls and the non-advanced adenoma group for S100A8 (p = 0.033) and (3) controls and the advanced adenoma group for S100A11 (p = 0.005). In the advanced adenoma group, differences between the healthy mucosa and adenomatous tissue were found in S100A6 (p = 0.002), S100A8 (p = 0.002), S100A9 (p = 0.021) and S100A11 (p = 0.029). Abnormal mRNA expression for different S100 proteins was identified in the pathological adenomatous tissue as well as in the morphologically normal large intestinal mucosa.

Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia.

BACKGROUND: Optimal therapy for colorectal carcinoma (CRC), a frequently diagnosed malignancy, does not exist. Some of colicins and microcins, ribosomally synthesized peptides by gramnegative bacteria, have shown significant biological activity specifically against different cancer cells in vitro and in vivo conditions. The aim of this prospective study was to evaluate natural colicin and microcin production by large intestinal mucosal bacteria in each stage of colorectal neoplasia and in those with a history of colorectal neoplasia. METHODS: A total of 21 patients with non-advanced adenoma (non-a-A; 16/21 with current and 5/21 with history of non-a-A), 20 patients with advanced colorectal adenoma (a-A; 11/20 with current and 9/20 with history of a-A), 22 individuals with CRC (9/22 with current and 13/22 with history of CRC) and 20 controls were enrolled. Mucosal biopsies from the caecum, transverse colon and the rectum were taken during colonoscopy in each individual. Microbiological culture followed. Production of colicins and microcins was evaluated by PCR methods. RESULTS: A total of 239 mucosal biopsies were taken. Production of colicins and microcins was significantly more frequent in individuals with non-a-A, a-A and CRC compared to controls. No significant difference in colicin and microcin production was found between patients with current and previous non-a-A, a-A and CRC. Significantly more frequent production of colicins was observed in men compared to women at the stage of colorectal carcinoma. A later onset of increased production of microcins during the adenoma-carcinoma sequence has been observed in males compared to females. CONCLUSIONS: Strains isolated from large intestinal mucosa in patients with colorectal neoplasia produce colicins and microcins more frequently compared to controls. Bacteriocin production does not differ between patients with current and previous colorectal neoplasia. Fundamental differences in bacteriocin production have been confirmed between males and females.

Serum S100A6, S100A8, S100A9 and S100A11 proteins in colorectal neoplasia: results of a single centre prospective study.

S100 proteins are involved in biological events related to colorectal carcinogenesis. Aim of this prospective study was to assess serum concentration of S100A6, A8, A9 and A11 proteins in patients with colorectal neoplasia. Eighty-four subjects were enrolled: 20 controls (average risk population with normal findings on colonoscopy; 7 men, 13 women, age 23-74, mean 55 ± 14), 20 patients with non-advanced colorectal adenoma (non-AA, 10 men, 10 women, age 41-82, mean 62 ± 11), 22 with advanced colorectal adenoma (AA, 15 men, 7 women, age 49-80, mean 64 ± 8) and 22 with colorectal cancer (CRC, 12 men, 10 women, age 49-86, mean 69 ± 10). Peripheral venous blood was obtained. Serum S100 proteins were investigated by enzyme immunoassay technique. Serum S100A6 was significantly lower in CRC (mean 8530 ± 4743 ng/L), p = .035 compared to controls (mean 11308 ± 2968 ng/L). Serum S100A8 was significantly higher in AA (median 11955 ng/L, IQR 2681-34756 ng/L), p = .009 and in CRC (median 27532 ng/L, IQR 6794-35092 ng/L), p < .001 compared to controls (median 2513 ng/L, IQR 2111-4881 ng/L). Serum S100A9 concentrations did not differ between any tested group and controls, p > .05. Serum concentration of S100A11 was significantly lower in non-AA (mean 3.5 ± 2.4 µg/L), p = .004 and in CRC (mean 3.4 ± 2.4 µg/L), p = .002 compared to controls (mean 5.9 ± 2.5 µg/L). Sensitivity and specificity for S100A8 protein in patients with CRC were 94% and 73%; positive predictive value 68% and negative predictive value 95%. Patients with colorectal neoplasia have significantly lower serum S100A6 and S100A11 levels, significantly higher S100A8 and unaltered serum S100A9 levels.

Pancreatic Cysts: Diagnostic Role of EUS-Guided Microforceps Biopsy and Confocal Laser Endomicroscopy.

Frequent use of high-quality cross-sectional imaging has led to a significant rise in diagnosis of pancreatic cystic lesions (PCLs). Despite the fact that enormous effort has been put into the research of PCLs within the last two decades and multiple guidelines have been developed, our clinical decision-making especially in regard to mucinous lesions remains limited. Currently, clinical assessment, cross-sectional imaging and EUS with fluid analysis (if appropriate) belong to the standard care in patients with PCLs. For differentiation of mucinous from nonmucinous cysts, the sensitivity of cytological investigation and CEA in the cyst fluid is 42% and 52-79%, respectively. Due to the limited accuracy, further diagnostic tools are warranted. Two EUS-guided approaches have been introduced recently. Through-the-(19-gauge EUS) needle Moray microforceps have been developed, and several studies have acknowledged their contribution to the correct diagnosis as they help to overcome limited cellularity of the EUS-guided cyst fluid aspiration and traditional cytology. Confocal laser endomicroscopy offers real-time images and seems to be a promising method for the diagnosis and differential diagnosis of pancreatic PCLs. Example images of the needle-based confocal laser endomicroscopy criteria for the diagnosis of PCLs have been suggested recently. Before both, Moray microforceps and confocal laser endomicroscopy can be widely accepted, further studies are necessary to determine the real diagnostic yield and the clinical efficacy.

Investigation of 23 Bile Acids in Liver Bile in Benign and Malignant Biliary Stenosis: A Pilot Study.

Differential diagnosis between benign and malignant biliary stenosis can be difficult in clinical practice. Histology of biopsy specimens is often indeterminate. Laboratory markers (serum bilirubin > 75 µmol/L, carbohydrate antigen 19-9 > 400 U/mL) and the length of stenosis (>15 mm) can be helpful but are not specific enough. The aim of this study was to investigate bile acids in liver bile of patients with benign and malignant biliary stenosis and controls without stenosis. A total of 73 patients entered the study: 7 subjects with benign biliary stenosis (6 men, 1 woman; 68 ± 13 years old), 21 with malignant biliary stenosis (15 men, 6 women; 72 ± 14 years old), and 45 patients without biliary stenosis (22 men, 23 women; 70 ± 13 years old); out of those, 25 subjects have and 20 do not have choledocholithiasis. Twenty-three different bile acids were investigated by high-performance liquid chromatography/mass spectrometry. Serum total bilirubin was significantly higher in patients with malignant biliary stenosis compared with nonstenotic controls (p = 0.005). Significant relationship (r > 0.7) was found between several pairs of bile acids. Significantly lower bile acid concentrations in malignant biliary stenosis compared to controls without stenosis were found for GLCA (p = 0.032), GUDCA (p = 0.032), GCDCA (p = 0.006), GDCA (p = 0.031), GHCA (p = 0.005), TUDCA (p = 0.044), and TDCA (p = 0.036). Significant difference in cholic acid was found between benign and malignant stenosis (p = 0.022). Analysis of bile acids might be helpful in the differential diagnosis of malignant and benign biliary stenosis. More patients need to be enrolled in further studies so that the real diagnostic yield of bile acids can be determined.

Pancreatic Adenocarcinoma: Epidemiology, Role of EUS in Diagnosis, Role of ERCP, Endoscopic Palliation.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide and is associated with a poor survival rate. The vast majority of pancreatic cancers are inoperable at the time of diagnosis. In the absence of metastatic disease, operability depends on the extent of local disease; in particular, the presence or absence of vascular and lymph node involvement. Adequate staging is vital in deciding an appropriate treatment plan. Cross sectional imaging including CT, MRI and PET-CT are commonly used for staging. However, EUS is a useful adjunct for accurate loco-regional staging in addition to allowing diagnostic tissue samples to be obtained. Emerging EUS-guided therapeutic techniques have opened up new horizons in the management of pancreatic malignancy. EUS guidance can be used for coeliac plexus neurolysis in patients with intractable pain and fiducial placement in directing stereotactic radiotherapy. The majority of patients with cancer of the pancreatic head present with biliary obstruction. ERCP can be used to drain the obstructed biliary system with plastic or metal stents and offers an opportunity to confirm the diagnosis by obtaining brush cytology and forceps biopsy specimens. EUS-guided choledocho-duodenostomy or hepatico-gastrostomy is increasingly being employed for draining the biliary system if ERCP is unsuccessful.

Exhaled Breath Condensate: Pilot Study of the Method and Initial Experience in Healthy Subjects.

Analysis of Exhaled breath condensate (EBC) is a re-discovered approach to monitoring the course of the disease and reduce invasive methods of patient investigation. However, the major disadvantage and shortcoming of the EBC is lack of reliable and reproducible standardization of the method. Despite many articles published on EBC, until now there is no clear consensus on whether the analysis of EBC can provide a clue to diagnosis of the diseases. The purpose of this paper is to investigate our own method, to search for possible standardization and to obtain our own initial experience. Thirty healthy volunteers provided the EBC, in which we monitored the density, pH, protein, chloride and urea concentration. Our results show that EBC pH is influenced by smoking, and urea concentrations are affected by the gender of subjects. Age of subjects does not play a role. The smallest coefficient of variation between individual volunteers is for density determination. Current limitations of EBC measurements are the low concentration of many biomarkers. Standardization needs to be specific for each individual biomarker, with focusing on optimal condensate collection. EBC analysis has a potential become diagnostic test, not only for lung diseases.

Mitotic and apoptotic activity in colorectal neoplasia.

BACKGROUND: Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. METHODS: A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. RESULTS: In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p < 0.05. Transformation of non-a-A into a-A did not lead to any further significant increase in apoptotic activity, but was related to significant increase in mitotic activity in upper part of crypts and superficial compartment. A significant decrease in apoptotic activity was detected in all three comparments of CRC samples compared to a-A; p < 0.05. No differences in mitotic and apoptotic activity between biopsies in healthy controls and biopsy samples from healthy mucosa in patients with colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. CONCLUSIONS: Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

Long-term outcomes of the randomized controlled trial comparing 5-aminolaevulinic acid and Photofrin photodynamic therapy for Barrett's oesophagus related neoplasia.

OBJECTIVE: Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett's oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT. METHODS: Biopsies were taken from original Barrett's segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR) ± radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia. RESULTS: Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6 cm, 14 patients with >6 cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6 cm, 13 patients with >6 cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p = .289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p = .472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p = .18; 90% vs. 76%; p = .26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p = .03). CONCLUSIONS: Initial response to PDT plays key role in long term outcome. RFA ± EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.

The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature.

BACKGROUND AND AIMS: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) has to date been recognized in only 8 families worldwide. Recently, different point mutations within the Ying Yang 1 (YY1) binding motif in promoter 1B of the APC gene were assigned as causal in 6 families with GAPPS. METHODS: We diagnosed GAPPS across 3 generations in a Czech white family. RESULTS: The proband's mother died of gastric cancer at 49 years of age. The proband died of gastric cancer at 56 years of age. All 3 of the proband's daughters inherited polyposis, involving exclusively the gastric fundus and body, with relative sparing of the lesser curve. The daughters have all been regularly surveyed endoscopically. Polyposis progressed rapidly with intestinal differentiated low-grade and high-grade dysplasia present on polypectomy specimens 5 years after the original diagnosis. On this basis, all 3 of the proband's daughters were scheduled for prophylactic total gastrectomy. Unfortunately, the middle daughter presented with generalized gastric adenocarcinoma and died at the age of 26 years. The other 2 daughters (aged 30 and 23 years) underwent total gastrectomy within 6 weeks of their sister's death; histology of surgical specimens showed gastric adenocarcinoma stage IA (pT1a, N0, M0) in both cases. Bi-directional Sanger sequencing of promoter 1B revealed a point mutation (c.-191 T>C) in all 3 daughters of the proband. CONCLUSIONS: Atypical endoscopic progression of the fundic gland polyposis, with the presence of dysplasia on polypectomy specimens and genetic testing with recently discovered mutations in promoter 1B of the APC gene might help clinicians to decide whether prophylactic gastrectomy should be performed.

Role of S100 Proteins in Colorectal Carcinogenesis.

The family of S100 proteins represents 25 relatively small (9-13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κß signaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy.