Cronkhite-Canada syndrome. Epidemiology, symptoms, morphology and therapy based on a case report and literature review

Juvenile polyposis was first described by Cronkhite and Canada in 1955. This disease is characterized by juvenile intestinal polyps and ectodermal abnormalities. The etiology of Cronkhite-Canada syndrome (CCS), however, is still not well understood. Interestingly among patients with CCS a significant correlation (16.5%) with intestinal carcinomas has been observed. Thus, malignant transformation and/or genetic predisposition may be involved in the initiation of the disease. In the following, epidemiology, symptoms, morphology and therapy of CCS are discussed. Our examinations are based on studies reported in the literature and on a case report of a female patient who developed a colon carcinoma 2 years after initial diagnosis of CCS.     

Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics in Germany

A survey of 1200 hospitals in Germany was undertaken to estimate the current standards of prevention and treatment of postoperative peritoneal adhesions. The 751 (62.2%) evaluated questionnaires showed a representative distribution according to postal zones and annual laparotomies. The rate of coeliotomies for adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2% and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and 22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are divided in patients with respective symptoms but without intestinal obstruction by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long intestinal tubes and plication procedures are applied by 43.9 and 33.7%, respectively. Medication is administered for routine prophylaxis of adhesion by 6%, for prevention of recurrencies by 17.2%. Although it has been revealed that adjuvant measures for prevention of adhesions are needed, as of today, no regimen has proofed its efficacy and gotten accepted for clinical usage.     

Granulation tissue polyposis associated with carcinoid tumours of the small intestine

We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy.     

Malignancy in Peutz-Jeghers syndrome? The pitfall of pseudo-invasion

Peutz-Jeghers syndrome is a malignancy-associated polyposis syndrome. We describe a histopathologic phenomenon easily encountered when examining the nature of Peutz-Jeghers polyps but that is underreported in the literature. This phenomenon of "pseudo-invasion" may mimic invasive carcinoma due to epithelial displacement and erroneously give the impression, both macroscopically and microscopically, that a malignancy is involved. This potential pitfall is illustrated by the case of a patient with Peutz-Jeghers syndrome who was thought to harbor a metastasizing adenocarcinoma in his small bowel with peritoneal metastasis as a perioperative finding. Histologic examination, however, revealed pseudo-invasion.     

Solvation of human serum albumin in aqueous alkylurea solutions

In order to list the negative emergency laparotomies, the records of 24,494 laparotomies performed from 1950 to 1989 were examined. 211 negative laparotomies were performed over this 40 years period: 49 for abdominal trauma, 42 for supposed intestinal obstruction, 44 for supposed peritonitis or visceral infection, 46 for presumed early post-operative abdominal complications and 30 for gastrointestinal bleeding. Over these 4 decades, the emergency laparotomy rate and negative laparotomy rate remained stable despite changes in the diagnostic tools, in the age of the patients and the frequency of their diseases.     

Epidermal nevus verrucosus and pubertas praecox

Carcinoma of the colon usually starts as a small nidus of malignant cells on the tip of adenomatous/villous polyps. The term "early cancer of the colon" is introduced as part of the concept that there are stages in the development of colon cancer and that it can and should be treated at an early stage. Removal of polyps at any point in their development up to the stage of early invasiveness represents the most favorable time for resection and cure.     

Erroneous laparotomies in emergency surgery

The retrospective analysis of case histories of 28 patients subjected to erroneous laparotomies in 1988-1992 has been done. The total number of patients, who had urgent abdominal operations for this period of time, was 5115. Atypical clinical course of the disease, improper diagnosis and interpretation of the disease symptoms, senile age of the patient are major causes of the erroneous laparotomies. To avoid erroneous laparotomy laparoscopy and ultrasound examination of abdominal cavity should be used widely, other medical specialists (urologist, gynaecologist) should be involved in diagnosis, especially in senile patients.     

Intestinal pseudoobstruction as a feature of myotonic muscular dystrophy

We report two cases of intestinal pseudoobstruction caused by visceral smooth muscle involvement due to myotonic muscular dystrophy. Two patients with myotonic muscular dystrophy presented with abdominal pain, distention, constipation, and vomiting. The exclusion of mechanical obstruction by plain abdominal radiography, contrast studies, and colonoscopy led to the diagnosis of intestinal pseudoobstruction. Diagnosis was confirmed by manometric and cineradiographic findings of abnormal intestinal motility. Conservative management including laxatives and cisapride led to the resolution of the pseudoobstruction syndrome and long-term remission without relapses during a two year follow-up. In patients with known myotonic dystrophy the occurrence of intestinal pseudoobstruction should be considered in order to avoid unnecessary laparotomies.     

Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice

Mutations in the human adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed Apc gene knockout mice that contained a truncation mutation at codon 716 (Apc(delta716)). The heterozygous mice developed numerous intestinal polyps. All microadenomas dissected from nascent polyps had already lost the wild-type allele, indicating the loss of heterozygosity (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). We also demonstrated that cyclooxygenase 2 is induced in the polyps at an early stage and plays a key role in polyp development (M. Oshima et al., Cell 87: 803-809, 1996). We have analyzed the process of polyp development in these mice both at morphological and molecular levels. A small intestinal microadenoma is initiated as an outpocketing pouch in a single crypt and develops into the inner (lacteal) side of a neighboring villus forming a double-layer nascent polyp. The microadenoma then enlarges and gets folded inside the villus. When it fills the intravillous space, it expands downward and extends into adjoining villi, rather than rupturing into the intestinal lumen. During this course of development, the basement membrane remains intact, and the labeling index of the microadenoma cells is similar to that of the normal crypt epithelium. As in the crypt cells, neither transforming growth factor beta1 nor its receptor type II is expressed in the microadenoma cells. No hot spot mutations in the K-ras gene are found in the microadenoma tissue during these early stages of polyp development. Essentially, the same results have been obtained for the colonic polyps as well. These results suggest that early adenomas in the Apc(delta716) polyps are very similar to the normal proliferating cells of the crypt except for the lack of directed migration along the crypt-villus axis.     

Ethanol inhibition of phagocytosis and superoxide anion production by microglia

A case of a symptomatic colonic lipoma causing recurrent abdominal pain and intestinal obstruction, not treated is reported. Lipomas are the most common mesenchymal benign tumors that can be found in the colon and are second as frequence only to the adenomatous polyps. In 65% of cases the lipomas are located in the large bowel and represent the most common cause of intestinal intussusception in the adult. Lipomas are most frequent in the right colon (40%-68%) an opposite distribution in comparison with adenocarcinomas and adenomatous polyps. When their diameter is more than 3 cm, lipomas become symtomatic. In lipomas less then 2 cm in diameter it is possible an endoscopic removal while for bigger sizes the surgical laparoscopic approach is recommended.     

Peutz-Jeghers syndrome: molecular analysis of a three-generation kindred with a novel defect in the serine threonine kinase gene STK11

The Peutz-Jeghers syndrome, phenotypically characterized by mucocutaneous pigmentation and hamartomatous polyposis, is an autosomal dominant disease with variable expression and incomplete penetrance. Moreover, affected patients are at increased risk for gastrointestinal and other malignancies. Recently, a mutated gene encoding abnormal forms of the novel serine threonine kinase STK11 has been identified as a genetic cause of Peutz-Jeghers syndrome. Here, we report the molecular analysis of the STK11 gene in a patient with Peutz-Jeghers syndrome, which in exon 1 revealed a guanine (G) insertion in the 5 G repeat of codons 51-53. The insertion leads to a frameshift with a premature TGA stop codon 324 bp downstream in codon 162, predicting the expression of a truncated protein without kinase activity. This heterozygous germline mutation was also found in the affected father and in one affected sister of the index patient, but not in any phenotypically unaffected family member or in unrelated control subjects. In DNA isolated from microdissected hamartomatous polyps of the index patient, exon 1 of the STK11 gene could not be amplified suggesting that both alleles of STK11 exon 1 were lost in the hamartomatous polyps. Identification of a STK11 gene mutation in an index patient offers the possibility of a predictive diagnosis, and initiation of specific screening programs in the genetically affected kindred.     

Central nervous system (CNS) involvement in SLE. The diagnostic role of antibodies to neuronal antigens

Dysplasia in inflammatory bowel disease (IBD) is categorized as either flat or associated with a raised lesion or mass (dysplasia-associated lesion or mass [DALM]). One specific subtype of a dysplasia-associated lesion or mass consists of isolated discrete nodules or polyps that are difficult to distinguish from sporadic adenomas. Because the clinical management of these two lesions is different, we performed this study to (1) evaluate the clinical presentation, pathologic features, and natural history of polypoid dysplastic lesions and sporadic adenomas in patients with IBD and (2) determine whether there are clinical, endoscopic, or pathologic findings useful in differentiating between these two lesions. The morphologic features of 89 benign polypoid epithelial neoplasms from 59 patients with IBD (51 with ulcerative colitis, 8 with Crohn's colitis) were evaluated and correlated with the clinical, endoscopic, and follow-up data. In a separate analysis, patients were categorized arbitrarily as having (1) a probable sporadic adenoma if the polypoid epithelial neoplasm was not located within areas of histologically proven colitis, (2) a probable IBD-associated polypoid dysplasia if the lesion developed within an area of colitis, and associated flat dysplasia or an adenocarcinoma was detected during follow-up evaluation or (3) an indeterminate polyp, which was seen in the remainder of the cases. The clinical, endoscopic, and histologic data were compared among these three patient and polyp subgroups. There were 35 males and 24 females (median age, 57 years; range, 27-85 years). Median duration of disease was 10 years. Forty-nine percent of the patients had pancolitis; 66% had histologically active disease at the time of presentation. Nearly 70% of patients had only one polyp; the majority occurred in either the left colon or the rectum (66%). Most polyps were described as a sessile nodule, whereas only 7 (7.8%) were pedunculated. Polyps ranged from 2 mm to 50 mm (median, 5 mm); most had a tubular architecture (84.3%) and contained low-grade dysplasia (64%). In addition, most polyps had mildly increased lamina propria and intraepithelial neutrophilic and mononuclear inflammation. At follow-up evaluation (40 patients; median follow-up time, 13 months; range, 1-78 months), a further neoplastic lesion developed in 20%; low-grade flat dysplasia was seen in 5 (12.5%), and adenocarcinoma developed in 3 (7.5%). However, dysplasia or adenocarcinoma did not develop in the patients who had polyps located outside of areas of histologically proven colitis. In addition, at least one more benign polypoid epithelial neoplasm developed in 15 of 40 patients (37.5%). Patients with probable IBD-associated polypoid dysplasia had a statistically significant (p < 0.05), longer disease duration than patients with probable sporadic adenoma. A statistically significant, higher proportion of polyps with tubullovillous or villous architecture, an admixture of normal and dysplastic epithelium at the surface of the polyps, and increased lamina propria mononuclear inflammation was noted in probable IBD-associated polypoid dysplastic lesions compared with those considered to be sporadic adenomas. Several clinical and pathologic features may be useful to help categorize a polypoid dysplastic lesion as a sporadic adenoma or an IBD-related neoplasm in a patient with IBD. This distinction is important because the natural history of these two lesions (as shown by the results of this study) and their subsequent management are quite different.     

Juvenile polyposis of the stomach: clinicopathological features and its malignant potential

AIMS: To clarify a clinical entity of juvenile polyposis of the stomach compared with generalised juvenile gastrointestinal polyposis. METHODS: The clinicopathological features of juvenile polyposis dominantly involving the stomach at initial presentation were reviewed in 12 patients (three new patients and nine from the literature). These were compared with 29 cases of generalised juvenile gastrointestinal polyposis. RESULTS: There were three men and nine women with juvenile polyposis of the stomach, aged 10-63 years. Hypoproteinaemia was present in nine patients, anaemia in seven, and a family history of intestinal polyposis in seven. No patient presented with a congenital abnormality. During the observation period, two patients developed colonic juvenile polyps. Gastric polyps invariably affected the antrum and extended to the fundus, eventually becoming more numerous, larger, and more pedunculated. Ten patients required gastrectomy for associated malignancy or uncontrolled protein losing gastropathy. Histological examinations of the resected specimens demonstrated neoplastic tissue arising from juvenile polyps in four of the 12 patients. Atypism in these mixed polyps varied from adenoma to well or moderately differentiated adenocarcinoma. CONCLUSIONS: Juvenile polyposis of the stomach has malignant potential, and may be a separate entity from generalised juvenile gastrointestinal polyposis.     

CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation

OBJECTIVE: The aim of this study was to compare the diagnostic accuracy of two-dimensional (2D) CT colonography and three-dimensional (3D) virtual colonoscopy with conventional colonoscopy in patients who have suspected colorectal neoplasms. SUBJECTS AND METHODS: Twenty patients were studied (eight women and 12 men; mean age, 53 years; range, 42-85 years). All patients had findings on conventional colonoscopy suggestive of colorectal carcinoma and underwent colonic CT within 3 hr of endoscopy. Two-dimensional CT colonography and 3D virtual colonoscopy images were generated from the same data set that was obtained from thin-section helical CT of the abdomen and pelvis after rectal insufflation of room air. Three-dimensional virtual colonoscopy images were obtained by downloading CT data to a workstation equipped with commercially available software. Volume- and perspective-rendering techniques were used to achieve interactive, 3D virtual "fly-through" examinations of the colonic mucosa. The results of 2D CT colonography and 3D virtual colonoscopy were compared with the findings of conventional colonoscopy and correlated with surgical and pathologic outcome where possible. RESULTS: Twenty masses (defined as intraluminal projections 2 cm or larger in diameter) and 15 polyps (defined as projections smaller than 2 cm in diameter) were identified in our study group. All masses and 14 of 15 polyps were successfully shown on 2D colonography. Three findings of polyps on 2D colonography were false-positive, and one was false-negative. Three-dimensional virtual colonoscopy revealed 19 of 20 masses and 13 of 15 polyps. On conventional colonoscopy, all 20 masses and 13 of 15 polyps were identified, with one false-positive finding of a malignant stricture in a normal colon. Complete examination of the colon was possible in 18 of 20 patients using the 2D technique and in 17 of 20 patients using 3D virtual colonoscopy, whereas conventional colonoscopy showed the entire colon in only 12 of 20 patients. CONCLUSION: Two-dimensional CT colonography and 3D virtual colonoscopy are complementary and effective techniques for examining the colon in patients with suspected colorectal carcinoma. CT techniques offer several advantages over conventional colonoscopy including the ability to detect abnormalities proximal to obstructing carcinomas, accurate localization of abnormalities within the colon, and good patient tolerance. These CT techniques may play an important role in future diagnosis of colorectal cancer and for screening patients at risk.     

Reducing the subconscious frown by endoscopic resection of the corrugator muscles

A prospective study concerning colorectal polyps in symptomatic patients was held at Lima, Perú, an area considered of low incidence for colorectal neoplasia. In 137 patients, 272 polyps were resected by colonoscopic polypectomy or surgery. 55.9% were adenomas, 40.4% non neoplastic polyps and 3.7% polypoid carcinomas. The distribution of polyps, and the incidence of dysplasia and malignant changes in the adenomas, were similar of that reported in areas with high incidence of colorectal cancer. A high proportion of patients with adenomas (21.4% had a synchronous advanced carcinoma, specially if there were multiple adenomas. The figure was lower in patients with only non neoplastic polyps (7.5%). There were no cases of "de novo" carcinoma. This evidence suggest that adenomas play an essential role in colorectal cancer histogenesis, even in areas of low incidence of this neoplasia.     

A normal initial colonoscopy after age 50 does not predict a polyp-free status for life

OBJECTIVES: The prevalence of colon polyps increases with age in the general population. It is unknown whether a lack of adenomatous polyps determined at one time point after the age of 50 is predictive of a subsequent low risk of polyp development. METHODS: Twenty-nine patients between ages 50 and 70 who had no prior history of polyps and had a normal colonoscopy at least 5 yr previously were recruited for follow-up colonoscopy to evaluate the incidence of neoplastic disease in this presumably low-risk group. RESULTS: The incidence of adenomatous polyps after a mean of 5.74 yr was 41.4% (95% confidence interval: 23.5-61.1%). A total of 20 adenomatous polyps were found in 12 patients. Seven polyps were 5 mm or more in size. CONCLUSIONS: We conclude that in patients with no history of colonic neoplasia who are 50 yr old, or older, the finding of a normal colonoscopy does not predict diminished risk of neoplasia.     

Neuroticism and extraversion as predictors of health outcomes in depressed primary care patients

A case with an alpha-fetoprotein (AFP)-producing carcinoma originating from the rectum is described. A 71-year-old male patient, who underwent a rectectomy for rectal carcinoma, developed space occupying lesions in the liver and a remarkable AFP elevation (220,000 ng/ml) in the 6th month postoperatively, and then expired one year later. Histologically, the rectal carcinoma consisted of well-differentiated adenocarcinomas, and contiguous cancerous cells proliferating in either a medullary or trabecular pattern. In the "trabecular" areas, localization of AFP was confirmed immunohistochemically. Results of concanavalin A or lens culinaris agglutinin affinity chromatography demonstrated that it was between a hepatic type and a yolk sac type, and was considered to be an intestinal type. This could have been an AFP-producing rectal carcinoma, in which the patient experienced liver metastasis at a relatively early postoperative period and died. This shows that AFP-producing rectal carcinomas are highly malignant, biologically, similar to AFP-producing gastric cancers.     

Endometriosis of the large intestine. A report of 2 clinical cases

Intestinal involvement of endometriosis requiring treatment is 5%, but only 0.7% needs intestinal resection. The authors report two cases of colic endometriosis and illustrate problems in diagnosis and management of this disease. Usually intestinal endometriosis takes the form of asymptomatic superficial serosal implants, encountered incidentally at laparotomy for other diseases, but it can also result in obstruction and occasionally bleeding. Any premenopausal woman with episodic bowel symptoms associated with gynecologic complaints should be suspected of endometriosis of the colon. Diagnosis can be suspected by double-contrast enema examination and colonoscopy with biopsy, although neither is likely to establish the diagnosis with certainty. In fact there are no radiologic or diagnostic imaging findings that are specific for endometriosis and unequivocal diagnosis requires microscopic examination. Differential diagnosis includes primary carcinoma of the colon and other benign diseases (pelvic inflammatory disease, diverticulitis, inflammatory bowel disease, pelvic abscess, polyps, etc.). The treatment of patients with uncomplicated, but symptomatic gastrointestinal endometriosis depends on the age of the patient and her childbearing attitude. Resection of the affected bowel should be done in patient with pain, bleeding, changes in bowel habits and intestinal obstruction and it is necessary to avoid neglecting a malignant tumor. Total abdominal hysterectomy and bilateral oophorectomy is the treatment of choice in the perimenopausal and menopausal women. In symptomatic women desiring children the only resection of involved colon may be appropriate treatment. In these subjects hormonal therapy can be useful.     

Hypophosphatasia: a developmental anomaly of alkaline phosphatase?

This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 +/- 9.77 U) and control infants (40.55 +/- 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 +/- 0.47 as compared with 19.10 +/- 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other. Three "inducers" of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting an in vivo action of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum. Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both. Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient's liver enzyme corresponded to the newborn's fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age-matched control subjects.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.