Familial Adenomatous Polyposis Coli Research Articles

POTENTIAL IDENTIFICATION OF PREVIOUSLY UNRECOGNIZED GARDNER SYNDROME DURING RADIOLOGIC EXAMINATION: A CASE REPORT

<h3>Background</h3> Familial adenomatous polyposis coli (FAP) is an autosomal dominant inherited disorder characterized by the development of multiple colonic adenomas with high risk for malignant transformation. FAP is caused by mutation of the adenomatous polyposis coli (APC) gene, a tumor suppressor. Several <i>APC</i> codon mutations result in a spectrum of intra- and extra-colonic manifestations. Gardner syndrome is a subset of FAP with potential extraintestinal findings, including epidermoid and sebaceous cysts, lipomas, supernumerary and impacted teeth, odontomas, jaw osteomas, and desmoid tumors/desmoplastic fibromas. Desmoplastic fibromas are benign aggressive neoplasms with potential tissue morbidity. <h3>Discussion/Conclusions</h3> A 15-year-old Caucasian male was referred to the oral and maxillofacial radiology clinic for radiologic evaluation of a left posterior mandibular radiolucency. The patient complained of pain at the site. His medical and dental histories was positive for biopsy of multiple epidermoid cysts, a fibrous tissue mass on the lower back, and 2 odontomas. Thus far, the patient had not been identified to be at risk for Gardner syndrome. Panoramic and cone beam computed tomography (CBCT) radiographs were made and showed nonuniform hyperdensities throughout the jaws, impacted teeth, and a well-defined, multilocular, radiolucent lesion at the angle of the left mandible demonstrating expansion. Impressions favored a benign aggressive entity of the left mandibular angle, and biopsy was recommended. The biopsy results were consistent with desmoplastic fibroma. Surgical resection was performed. Based on the collective findings, the diagnosis of Gardner syndrome was proposed. The patient was referred for genetic counselling and genetic testing for himself and his immediate family members. The results of molecular diagnosis are pending. Identification of FAP-related clinical and radiographic manifestations is crucial to early identification of FAP, which has important considerations in periodic evaluation for colon neoplasms and surgical prophylaxis. Early referral by an attentive radiologist can increase the opportunity for more effective disease management.

IFN/STAT signaling controls tumorigenesis and the drug response in colorectal cancer

Colorectal cancer (CRC) is caused by genetic alterations, and comprehensive sequence analyses have revealed the mutation landscapes. In addition to somatic changes, genetic variations are considered important factors contributing to tumor development; however, our knowledge on this subject is limited. Familial adenomatous polyposis coli (FAP) is an autosomal‐dominant inherited disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. FAP patients are classified into two major groups based on clinical manifestations: classical FAP (CFAP) and attenuated FAP (AFAP). In this study, we established 42 organoids from three CFAP patients and two AFAP patients. Comprehensive gene expression analysis demonstrated a close association between IFN/STAT signaling and the phenotypic features of FAP patients. Genetic disruption of Stat1 in the mouse model of FAP reduced tumor formation, demonstrating that the IFN/STAT pathway is causally associated with the tumor‐forming potential of APC‐deficient tumors. Mechanistically, STAT1 is downstream target of KRAS and is phosphorylated by its activating mutations. We found that enhanced IFN/STAT signaling in CFAP conferred resistance to MEK inhibitors. These findings reveal the crosstalk between RAS signaling and IFN/STAT signaling, which contributes to the tumor‐forming potential and drug response. These results offer a rationale for targeting of IFN/STAT signaling and for the stratification of CRC patients.

Uncovering Hereditary Tumor Syndromes: Emerging Role of Surgical Pathology.

With the increased use of modern next generation sequencing technologies in routine molecular pathology practice, the proportion of cancer cases with a definite or probable hereditary background seems to be steadily increasing. Currently, it is assumed that ≥10% of all malignancies develop in the setting of germline predisposition. Diagnosis and recognition of cancer predisposition syndromes relies not rarely on distinctive histopathological features that proved to be highly valuable and reproducible in uncovering those diseases that would otherwise have gone undetected by clinicians as being hereditary in nature. This is especially true in case of new mutations without suspicious family history. Example of such entities are fumarate hydratase-deficient renal cell carcinoma (RCC), succinate dehydrogenase-deficient RCC, hereditary gastrointestinal stromal tumor syndromes and many other diseases. It is remarkable that many of these inherited cancer syndromes do present as unifocal disease with highly variable age of onset so that many of them are misinterpreted as sporadic on clinical grounds. Availability of specialized cancer screening programs and disease-specific follow-up schemes for several hereditary cancer syndromes encourages the recognition of such disorders, so that "at risk patients" can be enrolled in such programs for early detection and timely intervention/ treatment of these malignancies which are in the majority of cases aggressive. In several conditions, as in familial adenomatous polyposis coli (FAP), well established prophylactic surgical interventions may be adopted to prevent the disease manifestations, highlighting the importance of the timely recognition of these potentially life-limiting neoplasms. In this review, the clinicopathological, demographic and histological features that are considered highly suggestive of a hereditary basis of "a neoplasm under consideration" are highlighted and discussed briefly. The details of some of these entities are in addition dealt with in reviews devoted to them in this special issue.

Per Rectal Bleeding in Children: Experiences in the Department of Paediatric Surgery in BSMMU

Per rectal bleeding is a frequently encountered clinical complaint in routine medical/surgical practice in paediatric patients. It has different aetiology in both extremes of age. This study was carried out in an attempt to find out causes, presentation and the proper management that can be offered to the affected infants and children.This retrospective study was carried out from January 2012 to December 2014 in the department of Paediatric Surgery of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. All patients presenting with the complaint of per rectal bleeding were included. But patients who needed emergency surgical intervention were excluded from this study. The data were reviewed for gender, age, causes of rectal bleeding and type, number, site, recurrence rate and the modality of treatment employed in children having colorectal polyp. Technetium-labeled red blood cells scans was used for the diagnosis of Meckel's Diverticulum. Complete blood picture and routine stool examination were done for all cases.Most polyp cases were diagnosed with digital rectal examination (DRE). Colonoscopy was performed for some cases in the Paediatric Gastroenterology Department of BSMMU. Also all the rectal polyps and colonic mucosal biopsies taken during colonoscopy submitted to histopathological examination. Per rectal bleeding was the chief complaint in 326 (1.5%) patients Out of 21,533 patients presenting to the outpatient department of Paediatric Surgery of BSMMU, Dhaka, Bangladesh over a period of three years. In this study, it was reviewed 326 patients, among them 208 (63.89%) were boys and 118 (36.19%) were girls. The male female ratio was 1.8:1. The ages ranged from 14 months to 14 years (mean age: 5.8years) at diagnosis. The most common aetiology was juvenile polyps which were found in 209 (64.11%) of the cases. It was to be found that anal fissure in 33 (10.12%) patients, rectal prolapse in 27 (8.2%) patients, non-specific colitis in 15 (4.60%) patients, Meckel's Diverticulitis in 3 (0.9%) patients, juvenile polyposis coli in 5 (1.5%) patients and familial adenomatous polyposis coli (FAP) in 4 (1.2%) patients. However, the cause of per rectal bleeding remained unknown suspecting chronic constipation in 30 (9.20%) patients. No statistically significant differences were observed between males and females as well as different age groups regarding the means of the underlying causes of per rectal bleeding in children(p &gt; 0.05). The prevalence of anal fissure in less than 2 years old patients and juvenile polyps in the 2-6 years old patients were significantly higher than the other causes (p &lt; 0.001). Other causes of per rectal bleeding prevailed in children were more than 2 years old. Colorectal polyps are common causes of per rectal bleeding in children. Proper physical examination including DRE along with the colonoscopy promotes both rapid and accurate diagnosis and the opportunity for immediate therapeutic measures.

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations.

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.

PWE-099 Desmoid Tumours in Familial Adenomatous Polyposis: Our Experience

Introduction Desmoid tumours are rare, benign, non-metastasising fibromatoses that affect 8–23% of patients with FAP. Desmoid disease poses significant morbidity through local compression and obstruction. There is an increased risk in females, pregnancy, those with germline mutation of the APC gene beyond codon 1399 and previous abdominal surgery. Management requires a balance of chemoprophylaxis and careful surgical intervention. We aimed to evaluate our local investigation and management of patients with FAP and desmoid tumours with respect to published guidance. Methods Patients with FAP who are on the colorectal database who were known to have desmoid disease were identified. Data was collected retrospectively from case notes, ICE and PACS systems. Management of each patient was compared to the St Mark’s Polyposis Registry guidance and published literature. Results There are 41 patients with FAP in our colorectal database (25 female, 16 male). Eleven patients from eight families were identified as having desmoid disease (six female, five male). Ten of these had desmoid tumours; one only postoperative desmoplastic reaction. The median age at diagnosis was 33 (range 8–49). Of the 10, all had undergone colectomy (five restorative proctocolectomy, three ileorectal anastomosis, two panproctocolectomy (eight prophylactically, two for malignancy). Three patients have had excision of desmoid tumours; all abdominal wall tumours. Six patients have been managed conservatively with observation, chemoprophylaxis and ureteric stenting for managing complications of compression. All patients have been kept under surveillance. One patient died following bowel perforation, one following recurrent bowel obstruction with inoperable mesenteric desmoid disease. Genetic testing was performed on the majority but specific mutational analysis was available for only 67% of patients. 6 of 8 of the patients with mutations in the desmoid region have developed desmoid tumours. Conclusion Mortality in our patient group from desmoid disease is higher than that from colorectal cancer and periampullary tumours, in line with national reported data. Prophylactic colectomy has been suggested to increase risk of developing desmoid disease especially with mutations in the desmoid region. Our results show that our patients are being managed appropriately but knowledge of location of germline mutation is strongly advised prior to offering prophylactic colectomy and management of solid desmoid tumours. In those with a higher risk of developing desmoid tumours, there may be an argument to continue endoscopic surveillance for as long as possible. Reference 1 Speake, et al . Desmoid tumours in patients with familial adenomatous polyposis and desmoid region adenomatous polyposis coli mutations. Br J Surg 2006; 93 (Suppl 1):21. Disclosure of Interest None Declared

CTNNB1 (β-Catenin)-altered Neoplasia: A Review Focusing on Soft Tissue Neoplasms and Parenchymal Lesions of Uncertain Histogenesis.

β-catenin (CTNNB1) is a key regulatory molecule of the Wnt signaling pathway, which is important for tissue homeostasis and regulation of cell proliferation, differentiation, and function. Abnormal stabilization and nuclear accumulation of β-catenin as a consequence of missense mutations or alternative molecular mechanisms occurs at a high frequency in a variety of epithelial cancers. In mesenchymal neoplasia, the role of β-catenin has been traditionally considered limited to desmoid-type fibromatosis. However, the spectrum of β-catenin-driven (β-catenin-altered) neoplasia of mesenchymal origin has been steadily widening to include, in addition to desmoid tumors, a variety of benign and intermediate-biology neoplasms of soft tissue (intranodal palisaded myofibroblastoma), head and neck (juvenile nasopharyngeal angiofibroma and sinonasal hemangiopericytoma/glomangiopericytoma), and ovarian (microcystic stromal tumor) origin. In addition, several old and newly reported distinctive site-specific β-catenin-driven parenchymal neoplasms of uncertain histogenesis have been well characterized in recent studies, including solid-pseudopapillary neoplasm of the pancreas and its recently described ovarian counterpart, sclerosing hemangioma of lung and calcifying nested stromal-epithelial tumor of the liver. This review addresses the most relevant pathobiological and differential diagnostic aspects of β-catenin-altered neoplasms with emphasis on site-specific histologic and biological variations. In addition, the morphologic overlap and analogy as well as distinctness between these uncommon tumors will be presented and discussed. Furthermore, a note is made on association of some of these lesions with hereditary tumor syndromes, in particular with the familial adenomatous polyposis coli.

Genetic Manipulation of Homologous Recombination In Vivo Attenuates Intestinal Tumorigenesis.

Although disruption of DNA repair capacity is unquestionably associated with cancer susceptibility in humans and model organisms, it remains unclear if the inherent tumor phenotypes of DNA repair deficiency syndromes can be regulated by manipulating DNA repair pathways. Loss-of-function mutations in BLM, a member of the RecQ helicase family, cause Bloom's syndrome (BS), a rare, recessive genetic disorder that predisposes to many types of cancer. BLM functions in many aspects of DNA homeostasis, including the suppression of homologous recombination (HR) in somatic cells. We investigated whether BLM overexpression, in contrast with loss-of-function mutations, attenuated the intestinal tumor phenotypes of Apc(Min/+) and Apc(Min/+);Msh2(-/-) mice, animal models of familial adenomatous polyposis coli (FAP). We constructed a transgenic mouse line expressing human BLM (BLM-Tg) and crossed it onto both backgrounds. BLM-Tg decreased adenoma incidence in a dose-dependent manner in our Apc(Min/) (+) model of FAP, although levels of GIN were unaffected and concomitantly increased animal survival over 50%. It did not reduce intestinal tumorigenesis in Apc(Min/) (+);Msh2(-/-) mice. We used the pink-eyed unstable (p(un)) mouse model to demonstrate that increasing BLM dosage in vivo lowered endogenous levels of HR by 2-fold. Our data suggest that attenuation of the Min phenotype is achieved through a direct effect of BLM-Tg on the HR repair pathway. These findings demonstrate that HR can be manipulated in vivo to modulate tumor formation at the organismal level. Our data suggest that lowering HR frequencies may have positive therapeutic outcomes in the context of specific hereditary cancer predisposition syndromes, exemplified by FAP.

Minimal access laparoscopic surgery for treatment of ulcerative colitis and familial adenomatous polyposis coli in children and adolescents.

Laparoscopic restorative proctocolectomy is standard surgical treatment for patients with ulcerative colitis (UC) and familial adenomatous polyposis coli (FAP). Scar burden can be minimized by reducing the number of laparoscopic ports. The aim of this study is to review the authors' experience with reduced-port laparoscopy in this setting and to compare it with conventional laparoscopy using multiple ports. Charts of pediatric patients undergoing colectomy for UC or FAP between 2009 and 2012 were retrospectively reviewed. Patients who had the operation performed through one or two multichannel ports were assigned to the minimal access (MA) study group. Patients who had four or five single-channel ports with or without an additional small laparotomy were assigned to the LAP group. Twenty-two patients were identified. Ages at first operation were 2-18 years (median, 13.5 years). There were no conversions to laparotomy and no mortality. Mean operative times for the MA and LAP groups, respectively, were 250 and 284 minutes for abdominal colectomy with end ileostomy (P=.15), 198 and 301 minutes for completion proctectomy with diverting loop ileostomy (DLI) (P=.26), and 455 and 414 minutes for proctocolectomy with ileal pouch-anal anastomosis and DLI (P=.72). A major complication requiring laparotomy occurred in 1 patient (9%) in the MA group and in 2 patients (18%) in the LAP group. Minimal access laparoscopic surgery for UC and FAP is safe and feasible. A slightly larger incision at the ostomy site facilitates extraction of the specimen and extracorporeal construction of a J-pouch. Operative times and hospital stay are comparable to those with multiport laparoscopy.

Adenocarcinoma arising in adenomatous polyposis coli

Familial adenomatous polyposis coli (FAP) is an inherited syndrome in which numerous polyps form mainly in colonic epithelium. Risk for cancer development gradually increases in such a condition if left untreated. Due to apparent symptoms such as rectal bleeding and abdominal pain, patients usually diagnosed at an early age. We report a FAP case with malignant transformation which is diagnosed at emergency department.

Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Colorectal Polyps in Urban Multiethnic Asian Population as Compared to Other Ethnicities during Screening Colonoscopy

Purpose: To find out the demographics, prevalence, and histology of colorectal polyps in multiethnic Asian population living in the urban area as compared to other ethnicities. Methods: Retrospective chart review identifying patients who had screening colonoscopy done for average risk of colon cancer during the year of 2012 at Thomas Jefferson University Hospital and its Methodist division in Philadelphia. High-risk patients like patients with inflammatory bowel disease (IBD), family history of colon cancer, familial adenomatous polyposis (FAP) coli, and hereditary non-polyposis colon cancer (HNPCC) syndrome, or with any genetic risk factor for colon cancer were excluded from the study. Data included patients' age, sex, race, presence of colorectal polyps, and their histology. These data was analyzed in computer software (SPSS). Each ethnicity was compared to Caucasians for all variables. Results: Total number of patients included in this study was 1,001. Out of these patients, 567 were Caucasians, 319 were African Americans, 37 were Hispanics, and 78 were Asians. Colon polyp was detected in 200 Caucasians, 92 African Americans, 14 Hispanics, and 18 Asians. The number of polyp was similar among different ethnicities, except in Asians who had significantly lower number of polyp than Caucasians (0.9 vs. 0.4; p=0.01). The age was similar (mean 58 years) in each group. In Asians, 38.5% were male, in Caucasians 42.3%, in African Americans 39.4%, and in Hispanics 8.1%. Many patients had more than one histology of polyps. Histologically, tubular adenoma was found in 19.4% of Caucasians, 14.1% of African Americans, 8% of Hispanics, and 6% of Asians. Hyperplastic polyp was found in 15.7% of Caucasians, 12.2% of African Americans, 10.8% of Hispanics, and 12.8% of Asians. Serrated adenoma was found in 1.1% of Caucasians and 1.6% of African Americans. Tubulovillous adenoma was found in 0.9% of Caucasians. High-grade dysplasia was found in 0.4% of Caucasians. Colon cancer was found in 0.2% of Caucasians. Tubular adenoma was significantly less in Asians (p=0.01) and Hispanics (p=0.05) compared to Caucasians. Conclusion: Asians had significantly less number of colorectal polyp and tubular adenoma compared to Caucasians. Hispanic patients were female predominant unlike other ethnicities. Hispanics had less tubular adenoma than Caucasians. Further larger study is warranted to investigate these phenomena.

Pathways of Colorectal Carcinogenesis

This review of the molecular and cellular changes in the different pathways of colorectal carcinogenesis sets out the classic adenoma-carcinoma sequence of the large bowel as a stepwise series of pathologic neoplastic changes associated with accumulation of genetic and epigenetic molecular alterations. The 2 major types of genomic instability found in colorectal cancers are chromosomal instability (CIN) and microsatellite instability (MSI). CIN is often associated with mutated APC. MSI is due to defective DNA mismatch repair. The associated familial cancer susceptibility syndromes are familial adenomatous polyposis coli, due to inherited APC mutations, and Lynch Syndrome or hereditary nonpolyposis colorectal cancer syndrome, due to inherited mutations in one of the mismatch repair genes (predominantly MLH1 and MSH2). In the CpG island methylator phenotype, a number of genes become transcriptionally silenced because of hypermethylation of their promoters, and this represents a key epigenetic mechanism of inactivation of tumor suppressor genes, including certain DNA repair genes. An overview of the contributions of CIN, MSI, and CpG island methylator phenotype to the different pathways of colorectal carcinogenesis allows categorization of colorectal cancers into 5 major groups on the basis of their molecular and pathologic characteristics.

The Italian National External Quality Assessment Program in Molecular Genetic Testing: Results of the VII Round (2010-2011)

Since 2001 the Istituto Superiore di Sanità established a quality assurance programme for molecular genetic testing that covers four pathologies: Cystic Fibrosis (CF), Beta Thalassemia (BT), Fragile X Syndrome (FX), and Familial Adenomatous Polyposis Coli (APC). Since 2009 this activity is an institutional activity and participation is open to both public and private laboratories. Seven rounds have been performed until now and the eighth is in progress. Laboratories receive 4 DNA samples with mock clinical indications. They analyze the samples using their routine procedures. A panel of assessors review the raw data and the reports; all data are managed through a web utility. In 2010 the number of participants was 43, 17, 15, 5 for CF, BT, FX, APC schemes respectively. Genotyping results were correct in 96%, 98.5%, 100%, and 100% of CF, BT, FX, and APC samples, respectively. Interpretation was correct in 74%, 91%, 88%, and 60% of CF, BT, FX, and APC reports, respectively; however in most of them it was not complete but a referral to genetic counseling was given. Reports were satisfactory in more than 60% of samples in all schemes. This work presents the 2010 results in detail comparing our data with those from other European schemes.

Familial adenomatous polyposis coli: Report of a rare entity

We report a sporadic case of a familial adenomatous polyposis coli (FAP) in a 25-year-old male who came with no family history of the same. FAP is the most common inherited adenomatous polyposis syndrome. Because of its rarity, the incidence in a developing country like ours is unknown. It is characterized by more than 100 adenomatous polyps and if left untreated carries a 100% risk of progression to colorectal cancer by the fourth decade. The early recognition and characterization of the polyposis syndrome is vital since early intervention and surgery will help in prevention against the development of invasive colorectal cancer.

Covering the Cover

Covering the Cover

The other colonic polyposis syndromes

Familial colorectal cancer syndromes have been increasingly recognized and through their characterization have contributed to our understanding of the genetic basis of colorectal cancer. The two main syndromes of familial adenomatous polyposis and hereditary non-polyposis coli are the commonest. There is however a number of lesser known syndromes described, which is the focus of this article.

A Porcine Model of Familial Adenomatous Polyposis

We created gene-targeted pigs with mutations in the adenomatous polyposis coli (APC) gene (APC) that are orthologous to those responsible for human familial adenomatous polyposis (FAP). One-year-old pigs with the APC(1311) mutation (orthologous to human APC(1309)) have aberrant crypt foci and low- and high-grade dysplastic adenomas in the large intestine, similar to the precancerous lesions that develop in patients with FAP. Dysplastic adenomas accumulate β-catenin and lose heterozygosity of APC. This large-animal, genetic model of FAP will be useful in the development of diagnostics and therapeutics for colorectal cancer. DNA sequence data: NCBI accession number GU951771.

Long-term survival in a case of malignant familial adenomatous polyposis coli with metachronous liver, lung and brain metastases

Long-term survival in a case of malignant familial adenomatous polyposis coli with metachronous liver, lung and brain metastases