[Surgical aspects of indications and techniques for adenomatous polyposis variants]. / Chirurgische Aspekte zu Indikation und Technik bei Varianten der adenomatösen Polyposis.

Due to the advances in molecular genetic diagnostics of adenomatous polyposis variants, identification of patients with a genetic predisposition and their at risk relatives is becoming increasingly important in clinical practice. Precise knowledge of the specific risk profile is gaining significance especially for surgeons and requires a clinically differentiated approach in order to correctly identify the indications for prophylactic surgery. In this article reference will be made to the technical details of the pouch operation rather than the decision-making process per se, since this has become common knowledge for specialized colorectal surgeons. Besides the more commonly known polyposis syndromes, such as familial adenomatous polyposis (FAP), surgeons should nowadays at least be able to clinically distinguish between attenuated and classical variants of FAP, be aware of MUTYH-associated polyposis (MAP) and also the new polyposis syndrome polymerase proofreading-associated polyposis (PPAP). Surgeons should be familiar with the specific indications and extent of surgery for prophylactic organ removal in the lower gastrointestinal tract in order to be able to competently advise patients.

Pigmentary disorders in China.

Because variations in the degrees of pigmentation occur in various regions of the body, there are different pigmentary diseases in various ethnic groups. We usually divide the disorders of melanin pigmentation into two types: hypermelanosis and hypomelanosis. These disorders may be due to genetic and environmental factors. Pigmentary disorders are more visible on the Chinese skin and are of great cosmetic concern to patients. In this article we introduce characteristic pigmentary disorders in China.

[Clinical classification of Peutz-Jeghers syndrome].

OBJECTIVE: To propose the clinical classification of Peutz-Jeghers syndrome (PJS). METHODS AND RESULTS: Retrospective analysis of 52 patients with PJS admitted in Nanfang Hospital from 1980 to 2003 was conducted. Twenty-four patients were found to have family history of PJS, who had a mean age of 19 years. In the PJS patients, the incidence of gastric polyps was 64.4%, colorectal polyps 76%, and small bowel polyps 95%. The number of polyps was above 50 in 19 of the 31 patients with gastric polyps, in 18 of the 38 patients with colorectal polyps, and in 8 of the 19 patients with small bowel polyps. The pathology of the majority of the polyps (63/108) was characterized by hamartomas, and the incidence of malignancy was 13.5% in the PJS patients. CONCLUSIONS: PJS can be classified according to family history and location, pathology, and number of the polyps. As most patients with over 50 polyps require surgical intervention, 50 polyps is recommended as the criteria for PJS classification. Endoscopic surgery may suffice for management of patients with fewer polyps (<50), while in patients with more polyps or small bowel polyps, open surgery combined with intraoperative endoscopic surgery is recommended.

Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.

CONTEXT: Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides management, especially surveillance and prophylactic surgery. OBJECTIVE: To systematically classify patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analysis in the context of central rereview of histopathology results. DESIGN, SETTING, AND PATIENTS: Prospective, referral-based study of 49 unrelated patients from outside institutions (n = 28) and at a comprehensive cancer center (n = 21), conducted from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A, STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of BRAF, MYH, and BHD, and rereview of polyp histology results were performed. MAIN OUTCOME MEASURES: Molecular, clinical, and histopathological findings in patients with unexplained polyposis. RESULTS: Of the 49 patients, 11 (22%) had germline mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had mutations in ENG, encoding endoglin, previously only associated with hereditary hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1). Of the 23 patients with hyperplastic/mixed polyposis, 2 had PTEN mutations. Substantial discrepancies in histopathology results were seen. CONCLUSIONS: Systematic molecular classification of 49 patients with unexplained hamartomatous or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG, for juvenile polyposis. Importantly, given the substantial proportion of patients found to have germline mutations, more extensive analysis of the known susceptibility genes is indicated. Rereview of histology results by a dedicated gastrointestinal pathologist should be considered routinely, as organ-specific surveillance rests on defining syndromic diagnosis.

[Hamartomatous polyposis syndromes]. / Sindromi poliposiche amartomatose.

Hamartomatous polyposis syndromes are characterized by an overgrowth of cells or tissues native to the area in which they normally occur. Peutz-Jeghers syndrome and juvenile polyposis are both characterized by the presence of hamartomatous polyps and increased risk of malignancy in the gastrointestinal tract. Cowden's disease is associated with germ-line mutations in the PTEN gene (10q22-23) and an increased risk of breast and thyroid malignancies. Ruvalcaba-Myhre-Smith syndrome is less common; controversy suggests that it may represent a variant of Cowden's disease.

Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice.

Recently, the sequential changes from adenoma to adenocarcinoma have been well studied in human colorectal carcinogenesis. To study the precise clonal changes from colorectal polyps to cancer, we have established an experimental system to maintain human colorectal polyps in severe combined immunodeficient (SCID) mice that have been improved by the selective inbreeding of C.B17-scid/scid homozygous male and female showing undetectable serum IgG and IgM (< 1 microgram/ml). Two of two solitary polyps from two nonhereditary colon polyp patients, four of five colon polyps from two Peutz-Jeghers' syndrome patients and one polypoid lesion from a familial polyposis coli (FAP) patient grew very slowly but steadily, at approximately one-tenth the rate of their malignant form, (i.e., adenocarcinoma), in the improved SCID mice and were maintained for a long period (more than 2 years), over several mouse generations. However, two polyps from FAP and Peutz-Jeghers' syndrome patients could not be transplanted further because of microinfection at the transplanted site due to incomplete sterilization of original human tumors prior to surgical operation (endoscopic polypectomy). Transplanted colon polyps had a semitransparent, soft and sticky appearance, with cells containing large amounts of mucin. Malignant transformation of human colon polyp to adenocarcinoma has not been observed during the maintenance period (about 2 years) in SCID mice. In the consecutively maintained human colon polyps, however, K-ras mutations were detected at codon 12, while these mutations were not found in their original polyps in the patients.

[Main forms and stages in the development of diffuse polyposis of the large intestine (problems of classification)]. / Osnovnye formy i stadii razvitiia diffuznogo polipoza tolstoi kishki (voprosy klassifikatsii).

Diffuse polyposis of the large intestine is a hereditary disease involving mostly young people and characterized by a high index of malignization. Previously proposed various classifications of the disease do not reflect completely the numerous important aspects of this pathology. On the basis of macro- and miroscopic studies on 186 operation preparations of the large intestine removed for diffuse polyposis 4 groups of the disease were distinguished: I--the largest group including polyposis with predominance of the cell proliferation processes (various kinds of adenomas--147 observations), II--polyposis with prevalence of secretion processes (juvenile polyps--24 observations), III--polyposis with both signs (10 observations); in this mixed group juvenile polyps alternated with glandular and glandular-villous polyps; group IV included 5 observations with Peuts-Jeghers syndrome.

Hereditary polypoid diseases of the gastrointestinal tract: a working classification.

Almost all published cases of hereditary intestinal polypoid diseases can be meaningfully classified into a relatively few distinct syndromes including familial polyposis of the colon, Peutz-Jeghers syndrome, and juvenile polyposis. Familial polyposis is characterized by the development of numerous adenomatous polyps of the colon and subsequent development of colorectal carcinoma in nearly all patients. Extracolonic manifestations are common but do not influence the premalignant nature of this syndrome. Peutz-Jeghers syndrome is identifiable by a combination of circumoral melanin pigmentation and hamartomatous polyps. These polypoid lesions have an unusually wide distribution and may occur in the respiratory, gastrointestinal, or genitourinary tract. There is a small but definite increased incidence of gastrointestinal cancer in these patients. Juvenile polyposis presents a more variable spectrum. In one form there is extensive intestinal involvement leading to diarrhea, inanition, and increased susceptibility to infection. Another form is limited to the colon and easily confused with familial polyposis. With the third form, there is involvement of the stomach, intestines, and colon, which makes it easily mistaken for the Peutz-Jeghers syndrome.