Treatment Of Familial Adenomatous Polyposis Research Articles

Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis.

Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP. To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP). We performed on a cohort (GSE111156) gene profile, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were defined as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A). Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune infiltration profile and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these five biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were finally identified associated with pink module, while only one biomarker (KLF2) associated with midnight module was identified. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR. We identified five potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP.

Familial Adenomatous Polyposis within the Pediatric Hereditary Polyposis Registry

Background/Objective: 
 Familial Adenomatous Polyposis (FAP) is a condition characterized by values exceeding hundreds of colorectal adenomatous polyps. FAP has a prevalence of 1 in 8,300 people, demonstrating an autosomal dominant inheritance pattern. This condition follows a pathogenic variation of the Adenomatous Polyposis Coli (APC) gene, located on chromosome 5q21-22. These mutations are heavily correlated with the incidence of colorectal carcinoma, requiring prophylactic colectomy. The management and treatment of FAP requires routine surveillance to reduce gastrointestinal polyp burden. The objective for this study is to characterize the current patient population at Riley with polyposis syndromes and assess clinical surveillance in patients diagnosed with FAP. 
 Methods: 
 Historical data from 2020-2022 GI clinical visits were reviewed using the diagnostic codes Family history of colonic polyps, Benign neoplasm of colon unspecified, and Other phakomatoses not elsewhere classified. These criteria identified 93 patients of which 64 patients were diagnosed with a hereditary polyposis syndrome for inclusion within the registry. Of the 64 patients, 42 had a diagnosis of FAP. Clinical data reviewed included the patient’s age of diagnosis, completion of genetic testing and follow-up, surgical treatment, routine endoscopic surveillance, and modes of imaging. 
 Results: 
 Results indicated a median age of diagnosis of 10 years, lower than previously reported national averages of 13.5-17 years. Evaluation of routine follow-up indicated a rate of endoscopy at 0.822 scopes per year and demonstrated that abdominal CT scans as well as abdominal X-rays were the most common supplemental modes of imaging. 
 Conclusion/ Future Directions: 
 The data from this registry will help direct care of patients with FAP, ensuring they receive treatment in accordance with national guidelines for routine surveillance and prophylactic colectomy. Moving forward, the intention is to expand the registry's date range to incorporate more patients and elaborate further on endoscopic findings for the specific subtypes of FAP.

Pharmacogenetic Variants Can Influence Optical Medication Use.

Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs. Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants' on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization. It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy. Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.

Surgical treatment of familial adenomatous polyposis in children: cross-sectional study

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by the APC gene mutation, characterized by colon adenomas and colorectal cancer, including in children. The issue of timing and indications for surgical treatment of FAP in childhood remains debatable.AIM: to identify predictors of surgery for FAP in pediatric patients.PATIENTS AND METHODS: a retrospective case-control study was conducted. The results of treatment of 50 children with FAP who were in the surgical department of the Russian Children's Clinical Hospital from January 2000 to April 2023 were analyzed. Two groups were formed: patients who underwent surgery of FAP under the age of 18 (case), and patients who did not undergo surgery at this age (control). We analyzed potential predictors: the age of manifestation, the clinical, the characteristics of adenomas, the anemia and family history, polyposis of the upper gastrointestinal tract.RESULTS: in the surgical group, the proportion of patients with more than 100 adenomas was higher (23 (88%) versus 11 (45%) (p=0.002)). It was revealed that the number of adenomas was more than 100 at the time of the first colonoscopy (OR 12 (95% CI (3–80), p=0.02) and the presence of colon bleeding (OR 5.8 (95% CI 1–35, p=0 .03) are independent predictors of colproctectomy in children.CONCLUSION: the number of adenomas over 100 and colon bleeding are independent predictors of colproctectomy in childhood.

Diagnosis and treatment of familial adenomatous polyposis in children

Diagnosis and treatment of familial adenomatous polyposis in children

Potential therapeutic benefit of ursodeoxycholic acid in the management of non hepato-biliary upper gastrointestinal disorders.

To examine the potential therapeutic effects of ursodeoxycholic acid (UDCA) on diseases of the esophagus, stomach, and duodenum. A search was conducted using EBSCO, Medline, PubMed, Google Scholar and Web of Science as well as international guidelines using MESH terms for treatment of UDCA for diseases of the upper gastrointestinal disorders in adult humans without regard to publication language or date restrictions. A total of 256 articles and 22 guidelines were initially identified, and 221 were excluded. Final revision of 13 articles and 22 guidelines confirmed that UDCA is found to have a cytoprotective role in Barret's esophagus within esophageal disorders, improves abdominal pain in functional dyspepsia, and does not alter Helicobacter pylori colonization or inflammation. Conflicting results are noted regarding the role of UDCA in the duodenum as chemopreventive treatment for familial adenomatous polyposis, with polyps regressing and their growth characteristics improving with low doses (10-25mg/kg/day). On the contrary, no positive effect was noted upon the combination with Celecoxib and with doses of 1000-2000mg or 20-30mg/kg/d. Gastrointestinal side effects were predominantly reported. No side effects necessitated hospitalization or ICU admission. Ursodeoxycholic acid has a limited therapeutic role in functional dyspepsia. There is promising evidence that it may serve as a chemopreventive for Familial adenomatous polyposis and Barret's esophagus, although further research is needed to confirm these findings.PROSPERO No.: CRD 42021267689.

Update on Surgical Management of FAP.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by pathogenic germline adenomatous polyposis coli mutation, and characterized with multiple adenomas in the colon and the rectum. Various genetic variants have been confirmed to be associated with corresponding FAP phenotypes, which play important roles in the diagnosis and surgical treatment of FAP. Generally, proctocolectomy is recommended for FAP patients at the age of 20s. Exceptionally, for patients with attenuated FAP, high-risk of desmoid, chemoprevention therapy, or other circumstances, surgery can be postponed. With the wide application of minimal invasive surgery in colorectal cancer, laparoscopic, robotic surgery, and natural orifice specimen extraction are proved to be feasible for FAP patients, but high-level evidences are needed to confirm their safety and advantages. In the times of precise medicine, the surgical management of FAP should vary with individuals based on genotype, phenotype, and clinical practice. Therefore, in addition to innovation in surgical procedures, investigation in links between genetic features and phenotypes will be helpful to optimize the surgical management of FAP in the future.

Novel read through agent: ZKN-0013 demonstrates efficacy in APCmin model of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a precancerous, colorectal disease characterized by hundreds to thousands of adenomatous polyps caused by mutations in the tumor suppressor gene adenomatous polyposis coli (APC). Approximately 30% of these mutations are premature termination codons (PTC), resulting in the production of a truncated, dysfunctional APC protein. Consequently, the β-catenin degradation complex fails to form in the cytoplasm, leading to elevated nuclear levels of β-catenin and unregulated β-catenin/wnt-pathway signaling. We present in vitro and in vivo data demonstrating that the novel macrolide, ZKN-0013, promotes read through of premature stop codons, leading to functional restoration of full-length APC protein. Human colorectal carcinoma SW403 and SW1417 cells harboring PTC mutations in the APC gene showed reduced levels of nuclear β-catenin and c-myc upon treatment with ZKN-0013, indicating that the macrolide-mediated read through of premature stop codons produced bioactive APC protein and inhibited the β-catenin/wnt-pathway. In a mouse model of adenomatous polyposis coli, treatment of APCmin mice with ZKN-0013 caused a significant decrease in intestinal polyps, adenomas, and associated anemia, resulting in increased survival. Immunohistochemistry revealed decreased nuclear β-catenin staining in the epithelial cells of the polyps in ZKN-0013-treated APCmin mice, confirming the impact on the β-catenin/wnt-pathway. These results indicate that ZKN-0013 may have therapeutic potential for the treatment of FAP caused by nonsense mutations in the APC gene. KEY MESSAGES: • ZKN-0013 inhibited the growth of human colon carcinoma cells with APC nonsense mutations. • ZKN-0013 promoted read through of premature stop codons in the APC gene. • In APCmin mice, ZKN-0013 treatment reduced intestinal polyps and their progression to adenomas. • ZKN-0013 treatment in APCmin mice resulted in reduced anemia and increased survival.

Results of surgical treatment for familial adenomatous polyposis

Aim: to analyze the results of surgery for familial adenomatous polyposis (FAP). Patients and methods: the case series study included 20 patients with FAP, 85 % of procedures with anastomosis and 15 % with a permanent ileostomy. Laparoscopic approach was used in 35 %. Results: the mean time of operation time was 243 minutes, the mean intraoperative blood loss was 244 ml, and the mean hospital stay was 17.2. Three (15.0 %) patients developed postoperative complications. Laparoscopic pro­cedures were advantageous in terms of intraoperative blood loss and faster recovery. The first polyps were detected in the rectal stump within 6-8 months after surgery, desmoid tumors within 24.3 months. Most patients had an acceptable quality of life with an mean number of stools per day 11.1. Conclusions: FAP is a complex problem of modern medicine requiring the teamwork of various medical specialists. Minimally invasive interventions for FAP have advantages over open procedures.

Immune Microenvironment: New Insight for Familial Adenomatous Polyposis

Currently, the main treatment for familial adenomatous polyposis (FAP) is surgery, however, surgery is far from ideal as there are many complications such as uncontrollable bowel movements, pouch inflammation, anastomotic stricture, and secondary fibroids. Therefore, it is necessary to further expand the understanding of FAP and develop new treatments for FAP. The immune microenvironment including immune cells and cytokines, plays an important role in FAP and the progression of FAP to adenocarcinoma, thus it may be a promising treatment for FAP. In the current review, we summarized the recent progress in the immune microenvironment of FAP.

A Two Generation of Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is a part of genetic polyposis syndrome which is caused by germline mutation in the adenomatous polyposis coli (APC) gene located in chromosome 5q21. The pathognomonic features is formation of hundreds to thousands of colorectal adenoma in late childhood and increase in size and number during adolescence. If left untreated, almost 100% patients will develop colorectal cancer by the age 50 years. We present a case of 26 year old male who complain of rectal bleeding, diarrhea, abdominal bloating, and has multiple polyps on colonoscopic finding. Two years ago, his father was diagnosed with polyposis coli and transverse colon adenocarcinoma. The patient was planned for preventive total colectomy. In conclussion, surgery remains the cornerstone treatment of FAP and surveillance program for early detection of cancer for all family member is very important to reduce colorectal cancer-related mortality.

Does ileoanal pouch surgery increase the risk of desmoid in patients with familial adenomatous polyposis?

Patients with familial adenomatous polyposis (FAP) may undergo either ileorectal anastomosis (IRA) or ileal pouch anal anastomosis (IPAA) depending on the degree of rectal involvement. Desmoid tumors (DTs) may arise postoperatively. Whether IPAA is associated with a higher risk of DTs as compared with IRA remains controversial. The purpose of this study was to determine whether IPAA increased the risk of DTs by analyzing the published data that compared IRA and IPAA as the primary treatment for FAP. A metaanalysis was performed to analyze the published data between 1989 and 2019. IRA and IPAA were compared with respect to the incidence of DTs. Eight retrospective studies with a total of 1072 patients were identified: 491 underwent IPAA and 581 IRA. There was no significant difference in the incidence of DTs between IPAA and IRA (11.81% vs. 9.47%, OR 0.95, P = 0.85). Meanwhile, the overall complication (42.97% vs. 36.76%, OR 1.32, P = 0.11), incidence of cancer (4.88% vs. 8.37%, OR 0.28, P = 0.26), and overall mortality (0.33% vs. 5.20%, OR 0.49, P = 0.53) were comparable too. Ileoanal pouch surgery is associated with similar risk of desmoid in patients with FAP after surgery.

Cellular Reconstruction of the Rectal Mucosa during surgical Treatment of Familial Adenomatosis of the Colon: 12 Years after the First Experience of Introduction into Clinical Practice

Aim. To study long-term results of surgical treatment of patients with familial adenomatous polyposis (FAP) with the cell reconstruction of the rectal mucosa.Materials and methods. 57 FAP patients were subjected to treatment, which involved colproctectomy, the preservation of the lower rectal ampulla, mucosectomy and the reconstruction of the mucosa by cell transplantation. Endoscopic monitoring was carried out, with the endoscopic observation covering the period of 19–120 months (median — 44.3 months). Morphological and immunohistochemical studies were conducted. The long-term functional results of treatment (anorectal manometry (profilometry)) were studied. The patients were surveyed using the SF-36 questionnaire to monitor the quality of their life.Results. Our results show that the use of cell transplantation leads to the reconstruction of the rectal mucosa over a fairly short time: in 44/57 (77.2 %) patients, the endoscopic picture corresponded to the unchanged rectal mucosa 4 weeks after the surgery. In 13/57 (22.8 %) patients, a complete mucosal reconstruction was achieved 8–12 weeks after the surgery. The absence of polyp growth in the preserved part of the rectum was observed. Late complications developed only in 5 (9.4 %) patients. Good functional results (acceptable frequency of defecation, lack of signs of anal incontinence and nocturnal defecation) were observed in 48/53 (90.6 %) patients. The quality of life was at a fairly high level in 90.6 % of patients.Conclusion. The proposed method of FAP treatment allowed the immediate and long-term treatment results to be improved significantly.

5-Hydroxymethylcytosine as a clinical biomarker: Fluorescence-based assay for high-throughput epigenetic quantification in human tissues.

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5-hydroxymethylcytosine (5-hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5-hmC quantification methods. Here we present and validate a fluorescence-based platform for high-throughput and cost-effective quantification of global genomic 5-hmC levels. We utilized the assay to characterize cancerous tissues based on their 5-hmC content, and observed a pronounced reduction in 5-hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof-of-concept data for treatment of familial adenomatous polyposis.

Laparoscopy adjuvant total colorectal resection for the treatment of familial adenomatous polyposis (FAP).

To discuss and evaluate the safety and value of laparoscopy adjuvant total colorectal resection for the treatment of familial adenomatous polyposis (FAP). From March 2010 to June 2015, 38 cases were retrospectively analyzed and divided into 2 groups, of which 17 cases used laparoscopy adjuvant total colorectal resection, and 21 cases used conventional laparotomy. Clinical data were obtained, and the safety and prognosis were observed. Seventeen cases using laparoscopy adjuvant total colorectal resection achieved success with no conversion to laparotomy and intraoperative complications. There was no significant difference in operation time between the two groups. There were significant differences in blood loss, the length of incision, postoperative recovery time of intestinal function and postoperative hospital stay between the two groups (P < 0.05). The trauma in laparoscopy group was less, and could recover faster, and there was no significant difference in complications between the two groups. In addition, there were no recurrence, distant metastasis and death in the follow-up period from 6 to 56months. Laparoscopy adjuvant total colorectal resection is more safe and feasible, which has minimal invasion and can recover fast.

Clinical Outcomes After Ileal Pouch-Anal Anastomosis in Pediatric Patients

BackgroundIleal pouch-anal anastomosis (IPAA) is the standard surgical reconstruction for patients with familial adenomatous polyposis (FAP) and ulcerative colitis (UC) who undergo total proctocolectomy (TPC). Although patients receive the same reconstruction, their postoperative complications can differ. We hypothesize that indication for TPC and other preoperative clinical factors are associated with differences in postoperative outcomes following IPAA. MethodsA retrospective cohort of pediatric patients who underwent proctocolectomy with IPAA from 1996 to 2016 was identified. Preoperative, operative, and postoperative clinical variables were collected. Univariate analyses were performed to evaluate for relevant postoperative clinical differences. ResultsSeventy-nine patients, 17 with FAP and 62 with UC, were identified. FAP patients spent a mean of 1125 ± 1011 d between initial diagnosis and first surgery compared to 585 ± 706 d by UC patients (P = 0.038). FAP patients took a mean of 57 ± 38 d to complete TPC with IPAA compared to UC patients at 177 ± 121 d (P < 0.001). FAP and UC patients did not differ in mean number of bowel movements at their 6-mo postoperative visit (4.7 ± 2.1 versus 5.6 ± 1.9, respectively [P = 0.134]). FAP patients were less likely to experience pouchitis (P = 0.009), pouch failure (P < 0.001), and psychiatric symptoms (P = 0.019) but more likely to experience bowel obstruction (P = 0.002). ConclusionsIPAA is a safe, restorative treatment for FAP and UC patients after TPC. Based on diagnosis and preoperative course, there are differences in morbidity in IPAA patients. Clinical data such as these will allow surgeons to help families anticipate their child's preoperative and postoperative courses and to maximize successful postoperative outcomes.

Advanced duodenal neoplasia and carcinoma in familial adenomatous polyposis: outcomes of surgical management.

In addition to the presence of neoplasia in the colon and rectum, patients with familial adenomatous polyposis (FAP) may develop numerous polyps and carcinoma within the upper gastrointestinal tract. The aim of the present paper was to review the incidence advanced duodenal polyposis or cancer and their surgical outcomes. A retrospective review of patients' records from our department was performed. Information was retrieved from a prospective collected data, including clinical (gender, age, family history), endoscopic [association with colorectal cancer (CRC), polyposis severity, age at diagnosis] and surgical management (age, time from the index surgery, type of procedure, morbidity). Duodenal adenomatosis at the time of surgery was classified according to Spigelman stages. In a group of 145 FAP patients, 8 (5.5%) had been surgically treated for duodenal advanced neoplasia [3] or cancer [5]. There were included 2 women and 6 men whose first endoscopic examination and diagnosis of advanced neoplasia/cancer was made at median ages of 47.3 [28-63] and 51.8 years, respectively. Duodenal carcinomas occurred later (55.8 years) when compared to advanced adenomatosis (45.3 years). Three patients were diagnosed due to symptoms, while the others were detected under endoscopic surveillance. Age interval between FAP treatment and duodenal neoplasia diagnosis was 15.3 years [0-47]. All but one patient underwent duodenopancreatectomy (DP). Two from the 7 patients undergoing DP died, one from pulmonary embolism 30 days after surgery and the other from recurrent T4N0 duodenal tumor. Thus, major operative morbidity and mortality were 12.5%. In this single-center Brazilian series of FAP patients: (I) advanced duodenal neoplasia or cancer requiring surgery occurred in 5.5% of patients; (II) when reaching the fifth decade of life, patients should be carefully evaluated to diagnose and treat early lesions; (III) in spite of the technical complexity of DP, operative morbidity is acceptable in experienced hands; and (IV) continuous surveillance is necessary during follow-up.

Longitudinal analysis of colon crypt stem cell dynamics in sulindac treated Familial Adenomatous Polyposis patients

The non-steroidal anti-inflammatory drug sulindac decreases size and number of adenomas after 4-6 months of treatment for familial adenomatous polyposis (FAP) patients. However, the underlying mechanism remains unknown. As stem cells are thought to be the tumor precursor cells, visualizing their behavior is crucial for monitoring tumor progression. Increased tag diversity in inactive genes is indicative of a protracted clonal evolution and consequently, increased risk for tumor formation. Therefore, the effect of sulindac on stem cell dynamics was studied. Normal appearing single crypts were laser microdissected in placebo- and sulindac- treated FAP patient tissue after which the methylation patterns were visualized by Next Generation Sequencing. A significant difference in tag diversity over time was found in the sulindac group compared to the placebo group (*p = 0.018), indicative of a shortened clonal evolution treated sulindac. The rate of change in tag diversity over time was correlated with polyp number change over time. No significant difference over time was observed in the percent methylation when comparing placebo vs sulindac. In conclusion, daily sulindac administration in FAP patients significantly altered colorectal stem cell dynamics, which might explain the chemopreventive action of this drug indicating that tag diversity may be used as a predictive biomarker.

FORMULATION AND DEVELOPMENT OF MICROSPHERES FOR THE TREATMENT OF FAMILIAL ADENOMATOUS POLYPOSIS

Objective: Familial adenomatous polyposis (FAP) also known as familial polyposis coli, is a hereditary disease characterized by progressive appearance of numerous polyps mainly in the large intestine. Polyps are initially benign but can easily become cancerous and as such it is a life threatening condition. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor is thought to induce cell death, and thus prevent or delay the growth of polyps. So in the present study celecoxib loaded microspheres were prepared using control release Hydroxy propyl methyl cellulose (HPMC K4M) and pH dependent polymer eudragit L 100-55 in different ratios (1:1 to 1:4) respectively. The main objective of the study is to identify the polymer concentration required to prevent the drug release in stomach region and promotes in intestinal region.Methods: Emulsification solvent evaporation method was selected for the preparation and all the optimized formulations were evaluated for drug-polymer interactions, percentage yield, micrometric properties, entrapment efficiency, particle size analysis, differential scanning calorimetry and in vitro dissolution study.Results: Drug and polymer interactions were evaluated by using FTIR and DSC. The FTIR spectrum and DSC thermograms stated that drug and polymer are compatible to each other. The micrometric properties of drug loaded microspheres were carried out and they were found to be as the angle of repose (18.26 °-40.69 °), bulk density (0.2846-0.3875), tapped density (0.4111-0.5428), Carr’s index (9.66-14.77), Hausner’s ratio (1.112-1.2642) which were within the limits. In vitro dissolution, drug release was found to be from 4.5 to 6.5 h for the prepared four formulations (F1–F4). From the kinetic data modeling the order of drug release was found to be zero order and korsmeyer-peppas with n value above 0.5 for all the formulations indicating non-fickian diffusion.Conclusion: All the result demonstrated that celecoxib microspheres can be effectively used in the treatment of familial adenomatous polyposis

Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan

We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan. This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000-2006) and Group 2 (2007-2012) based on their date of surgery. Age at the time of prophylactic surgery was 27 and 31years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13%, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23%, respectively; P=0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40%, respectively). There was no surgical mortality in either group. Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.