Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females.

BACKGROUND AND AIMS: Upper gastrointestinal adenocarcinomas show an unexplained male predominance that is more apparent in oesophagus than stomach and in intestinal than diffuse histological subtype. We have conducted a population-based study to determine whether the gender phenomenon is primarily related to the anatomical site or the histological subtype. METHOD AND MATERIALS: Of 3270 gastric and oesophageal cancers recorded in the West of Scotland Cancer Registry, 1998-2002, 812 were randomly selected for detailed analysis. The Lauren histological subtype of adenocarcinoma was determined by reviewing 1204 original reports and 3241 biopsies. RESULTS: Analysis included 405 non-cardia cancers, 173 cardia cancers and 209 oesophageal adenocarcinomas. Crude incidence rate of intestinal subtype was higher in males (23.86/100,000 person-years) versus females (9.00/100,000 person-years), giving a male/female (M/F) ratio of 2.65 whereas diffuse subtype was similar for both genders (5.58 vs 5.20/100,000 person-years) yielding M/F of 1.07. The M/F ratios for oesophageal, cardia and non-cardia gastric cancer were 3.5, 2.0 and 1.6, respectively. Multiple logistic regression indicated that the odds of male gender was related to the histological subtype rather than anatomical location (odds ratio 2.6, 95% confidence interval 1.78 to 3.9). Curve fitting of the age-specific incidence of intestinal subtype indicated that similar functions describe the rise in incidence with age in males and in females. However, the age-specific incidence of female intestinal subtype was delayed by 17.3 years. The M/F ratio of intestinal subtype was 3.41 at age <50 years, peaked at 7.86 at age 50-59 years and then showed a progressive decrease after 50-60 years of age. CONCLUSION: Male predominance of upper gastrointestinal adenocarcinoma is related to the intestinal histological subtype rather than tumour location and is due to marked delayed development of this subtype in females prior to 50-60 years of age.

Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre.

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.

Manipulation of colonic bacteria and volatile fatty acid production by dietary high amylose maize (amylomaize) starch granules.

AIMS: To study the effects of amylomaize starch and modified (carboxymethylated and acetylated) amylomaize starches on the composition of colonic bacteria and the production of volatile fatty acids, in mice. METHODS AND RESULTS: Balb/c mice were fed with experimental diets containing various amount of amylomaize and modified amylomaize starches. Colonic bacterial populations and short-chain fatty acids were monitored. Results showed that the increases in indigenous bifidobacteria were detected in mice fed all starches tested; however, the highest numbers were observed in the group fed with 40% unmodified amylomaize starch. The starch type influenced the populations of indigenous Lactobacillus, Bacteroides and coliforms. High Lactobacillus numbers were achieved in the colon of mice fed with high concentration of amylomaize starch. Acetylated amylomaize starch significantly reduced the population of coliforms. In addition, orally dosed amylomaize utilizing bifidobacteria reached their highest levels when fed together with amylomaize or carboxymethylated amylomaize starch and in both cases butyrate levels were markedly increased. CONCLUSIONS: These results indicate that different amylomaize starches could generate desirable variation in gut microflora and that particular starches may be used to selectively modify gut function. SIGNIFICANCE AND IMPACT OF STUDY: Amylomaize starch appeared to enhance the desirable composition of colonic bacteria in mice, and suggested it possessed the potential prebiotic properties. Therefore, resistant starch and its chemical derivatives may exert beneficial impacts to the human colon.

Starches, resistant starches, the gut microflora and human health.

Starches are important as energy sources for humans and also for their interactions with the gut microflora throughout the digestive tact. Largely, those interactions promote human health. In the mouth, less gelatinised starches may lower risk of cariogensis. In the large bowel, starches which have escaped small intestinal digestion (resistant starch), together with proteins, other undigested carbohydrates and endogenous secretions are fermented by the resident microflora. The resulting short chain fatty acids contribute substantially to the normal physiological functions of the viscera. Specific types of resistant starch (e.g. the chemically modified starches used in the food industry) may be used to manipulate the gut bacteria and their products (including short chain fatty acids) so as to optimise health. In the upper gut, these starches may assist in the transport of probiotic organisms thus promoting the immune response and suppressing potential pathogens. However, it appears unlikely that current probiotic organisms can be used to modulate large bowel short chain fatty acids in adults although resistant starch and other prebiotics can do so. Suggestions that starch may exacerbate certain conditions (such as ulcerative colitis) through stimulating the growth of certain pathogenic organisms appear to be unfounded. Short chain fatty acids may modulate tissue levels and effects of growth factors in the gut and so modify gut development and risk of serious disease, including colo-rectal cancer. However, information on the relationship between starches and the microflora is relatively sparse and substantial opportunities exist both for basic research and food product development.

The protective effects of high amylose maize (amylomaize) starch granules on the survival of Bifidobacterium spp. in the mouse intestinal tract.

The possibility of using high amylose maize starch granules as a delivery system for probiotic bacteria has been investigated using Bifidobacterium spp. LaftiTM 8B and LaftiTM 13B which were isolated from a healthy human. The Bifidobacterium cells were able to adhere to the amylomaize starch granules and were also able to hydrolyse the starch during growth. Initially, in vitro studies were carried out by studying the survival of strains Bifidobacterium LaftiTM 8B and LaftiTM 13B when exposed to pH 2.3, 3.5 and 6.5 as well as 0.03 and 0.05% w/v bile acids. Both strains were grown either in the absence or presence of high amylose maize starch granules, then mixed with the high amylose maize starch granules and exposed to acidic buffers or bile acid solutions. It was shown that growth in and the presence of high amylose maize starch granules led to enhanced survival of strains LaftiTM 8B and LaftiTM 13B. Subsequently, survival in vivo was monitored by measuring the faecal level of Bifidobacterium LaftiTM 8B after oral administration of the strain to mice. A sixfold better recovery of strain LaftiTM 8B from mice faeces after oral dosage was noted for cells grown in amylose-containing medium compared with controls. It was concluded that high amylose maize starch granules contributed to enhanced survival of Bifidobacterium sp. LaftiTM 8B and LaftiTM 13B.

In vitro utilization of amylopectin and high-amylose maize (Amylomaize) starch granules by human colonic bacteria.

It has been well established that a certain amount of ingested starch can escape digestion in the human small intestine and consequently enters the large intestine, where it may serve as a carbon source for bacterial fermentation. Thirty-eight types of human colonic bacteria were screened for their capacity to utilize soluble starch, gelatinized amylopectin maize starch, and high-amylose maize starch granules by measuring the clear zones on starch agar plates. The six cultures which produced clear zones on amylopectin maize starch- containing plates were selected for further studies for utilization of amylopectin maize starch and high-amylose maize starch granules A (amylose; Sigma) and B (Culture Pro 958N). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect bacterial starch-degrading enzymes. It was demonstrated that Bifidobacterium spp., Bacteroides spp., Fusobacterium spp., and strains of Eubacterium, Clostridium, Streptococcus, and Propionibacterium could hydrolyze the gelatinized amylopectin maize starch, while only Bifidobacterium spp. and Clostridium butyricum could efficiently utilize high-amylose maize starch granules. In fact, C. butyricum and Bifidobacterium spp. had higher specific growth rates in the autoclaved medium containing high-amylose maize starch granules and hydrolyzed 80 and 40% of the amylose, respectively. Starch-degrading enzymes were cell bound on Bifidobacterium and Bacteroides cells and were extracellular for C. butyricum. Active staining for starch-degrading enzymes on SDS-PAGE gels showed that the Bifidobacterium cells produced several starch-degrading enzymes with high relative molecular (M(r)) weights (>160,000), medium-sized relative molecular weights (>66,000), and low relative molecular weights (<66,000). It was concluded that Bifidobacterium spp. and C. butyricum degraded and utilized granules of amylomaize starch.

A high amylose (amylomaize) starch raises proximal large bowel starch and increases colon length in pigs.

Young male pigs consumed a diet of fatty minced beef, safflower oil, skim milk powder, sucrose, cornstarch and wheat bran. Starch provided 50% of total daily energy either as low amylose cornstarch, high amylose (amylomaize) cornstarch or as a 50/50 mixture of corn and high amylose starch. Neither feed intake nor body weight gain as affected by dietary starch. Final plasma cholesterol concentrations were significantly higher than initial values in pigs fed the 50/50 mixture of corn and high amylose starch. Biliary concentrations of lithocholate and deoxycholate were lower in pigs fed high amylose starch. Large bowel length correlated positively with the dietary content of high amylose starch. Concentrations of butyrate in portal venous plasma were significantly lower in pigs fed high amylose starch than in those fed cornstarch. Neither large bowel digesta mass nor the concentrations of total or individual volatile fatty acids were affected by diet. However, the pool of propionate in the proximal colon and the concentration of propionate in feces were higher in pigs fed amylose starch. Concentrations of starch were uniformly low along the large bowel and were unaffected by starch type. In pigs with cecal cannula, digesta starch concentrations were higher with high amylose starch than with cornstarch. Electron micrographic examination of high amylose starch granules from these animals showed etching patterns similar to those of granules obtained from human ileostomy effluent. It appears that high amylose starch contributes to large bowel bacterial fermentation in the pig but that its utilization may be relatively rapid.

Detection and distribution of heat shock proteins 27 and 90 in human benign and malignant prostatic tissue.

OBJECTIVE: To determine whether it is possible to predict the behaviour of prostate tumours by identifying cellular characteristics, specifically specific heat shock proteins (HSPs). MATERIALS AND METHODS: An immunohistochemical study staining for HSP 27 and 90 was undertaken on 15 benign and 13 malignant samples of freshly frozen prostatic tissue obtained from patients with a similar age range in each group (benign, mean age 71.6 years, range 61-86; malignant, mean age 72.7 years, range 58-87). Gleason scores for the tumours ranged from 2 to 8. RESULTS: Consistent patterns of cytoplasmic staining were seen in all sections of tissue from benign prostatic hyperplasia (BPH). The stroma stained strongly positive for HSP 27, but negatively for HSP 90 and glandular epithelium showed positive apical staining for both HSPs. Stromal patterns in prostatic carcinoma tissue were similar to that of BPH tissue for both HSP 27 and 90. Areas of prostatic intra-epithelial neoplasia stained as strongly as did adjacent areas of BPH. For HSP 27, there was varied staining of individual epithelial cells, suggesting cellular heterogeneity, with an apparent reduction in staining with increasing Gleason score and invasiveness. For HSP 90, this pattern was less marked, with a predominance for positive staining throughout all grades of carcinoma. CONCLUSIONS: The distribution of HSPs, primarily HSP 27, may aid in identifying different cell populations within prostatic carcinomas and thus help forecast biological behaviour.

Helicobacter pylori in renal transplant recipients.

An unselected group of 33 renal transplant recipients were examined by upper gastrointestinal endoscopy at between two and four months after transplantation. All abnormal lesions were documented and biopsied and, in addition, random biopsies were obtained from the gastric antrum and from the first part of the duodenum. The biopsies were examined and graded for gastritis and duodenitis and the presence of Helicobacter pylori was noted. Duodenitis was identified in 16 patients and gastritis in 10; four patients had a gastric ulcer. Helicobacter was identified in the gastric antrum of 16 patients (48%) and was strongly associated with symptomatic dyspepsia, with gastritis, and with peptic ulceration. There was no relationship between H pylori and prednisolone dose, serum cyclosporine levels, or renal function. H pylori was found to be common in the upper GI tract of renal transplant recipients and may explain the high prevalence of upper GI pathology in these patients. It is interesting to speculate that immunosuppression may contribute to this, although there is no direct evidence from this study to support this theory.

Ki-67 antibody immunostaining in benign and malignant human prostatic disease.

Indices of mitotic potential may improve prognostic discrimination in patients with malignant disease. Ki-67 is a monoclonal antibody directed against an unknown proliferation antigen which has been shown to be a measure of mitotic potential. Sixty-four benign and eighty malignant prostatic biopsies were stained with the Ki-67 antibody. Nuclear and cytoplasmic staining was identified in benign and malignant biopsies using immunoalkaline phosphatase and immunoperoxidase staining reactions. Nuclear staining was identified in 14 benign and 44 malignant biopsies. Nuclear staining for Ki-67 was seen in 36% of biopsies with Gleason histological score (GHS) 2-4, 71% with GHS 5-7 and 62% with GHS 8-10. Nuclear staining was associated with advanced local disease stage, but not with metastatic disease stage. Clinical follow-up is required to establish the value of Ki-67 immunostaining as a prognostic determinant in prostatic cancer.

Nasal peripheral T-cell lymphoma: a 20-year review of cases treated in Scotland.

The nasal peripheral (post-thymic) T-cell lymphoma is an important cause of the midline granuloma syndrome (MGS), in which ulceration and destruction of the tissues of the nose and paranasal sinuses occurs. We reviewed the histology of 9 cases of the MGS treated with radiotherapy, and, using immunocytochemistry, showed 8 cases to be peripheral T-cell lymphomas (PTCL) and 1 a B-cell lymphoma. All patients received radiotherapy and 2 died shortly after treatment from unrelated causes. Two patients with T-cell lymphoma and the solitary case of B-cell lymphoma achieved long-term disease-free survival. The 4 remaining cases of T-cell lymphoma relapsed locally at a median interval of 3.5 months despite megavoltage irradiation of 45-50 Gy (in 3 cases) and inclusion of uninvolved paranasal sinuses and the nasopharynx in the field (in 2 cases). All patients with local relapse achieved, and remain in, remission after treatment with alkylating agents and prednisolone. The disappointing response of some cases of nasal T-cell lymphoma to radiotherapy has been reported by others, and this may be due partly to the heterogeneity of nasal lymphomas. We are unable to provide clear guidelines for treatment but suggest that a role exists for initial treatment with oral alkylating agents and steroids in newly diagnosed cases.

Transforming growth factor-alpha expression in benign and malignant human prostatic disease.

Investigation of biological variables in prostatic disease may not only prevent patients with a good prognosis being overtreated, but allow better selection of appropriate therapy, and may identify potential targets for novel therapies. This study investigates the growth factor transforming growth factor-alpha (TGF alpha) expression in benign and malignant prostatic biopsies using both radioimmunoassay and immunohistochemistry, considering its role in malignant epithelial transformation and as a prognostic indicator. Biochemical methods were less satisfactory than the more selective immunohistochemical methods, due to the heterogeneity of prostatic tissue. Seventy-one percent of benign biopsies (range 0-18.62ng/mg DNA) and 69% of malignant biopsies (range 0-11.1ng/mg DNA) had detectable levels of TGF alpha using radioimmunoassay. Immunohistochemical staining for TGF alpha identified expression in 15% of benign (4 out of 27) and 53% malignant biopsies (18 out of 34). Positive staining was also identified in premalignant lesions and within stromal elements, thus implying the factor's role in autocrine/paracrine growth and/or malignant transformation. Immunostaining for TGF alpha may enhance detection of premalignant lesions and small foci of malignant glands which are otherwise difficult to identify using standard histopathological techniques.

Anastomotic suture materials and experimental colorectal carcinogenesis.

Local tumor recurrence following restorative surgery for colorectal cancer may occasionally result from the promotion of a neoplastic lesion in a zone of proliferative instability adjacent to the anastomosis. The aim of this study was to compare the influence of three anastomotic suture materials, including stainless steel (as a model of surgical stapling), on colorectal carcinogenesis in an experimental animal model. The transmural implantation of stainless steel sutures into the distal descending colon of albino Swiss rats during the postinitiation phase of tumor induction resulted in significantly fewer animals exhibiting perianastomotic tumors 12 weeks later (3 of 21 animals) when compared with either polyamide (Nurolon; Ethicon, Edinburgh, United Kingdom) (14 of 20 animals; P less than 0.001) or polyglycolic acid (Dexon Plus; Davis and Geck, Gosport, United Kingdom) sutures (17 of 21 animals; P less than 0.001). The findings were similar when the same materials were used to resuture a longitudinal colotomy. For both operative procedures, the type of suture material had no influence on the incidence of large bowel tumors distant from the anastomotic site. These results suggest that stainless steel staples may promote fewer perianastomotic large bowel tumors than certain more conventional suture materials and, therefore, may be safely employed in colorectal cancer surgery.

Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage.

An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, range 0-5 minutes) than in the control group (median 4 minutes, range 2-8 minutes) (p less than 0.001). Skin bleeding times were similar in the two groups (medians 4 minutes in patients with haemorrhage and 4.5 minutes in controls). In 21 patients with haemorrhage who were taking non-steroidal anti-inflammatory drugs, the median gastric mucosal bleeding time (2.5 minutes, range 1.0-5.0 minutes) was similar to that in 26 patients with haemorrhage not associated with these drugs (2.0 minutes, range 0.0-5.0 minutes). These results show that gastric mucosal haemostasis is accelerated in response to haemorrhage in the upper gastrointestinal tract, even in patients taking nonsteroidal anti-inflammatory drugs. This enhanced gastric haemostasis probably reflects a local protective response to minimise blood loss from the bleeding lesion.

Nucleolar organizer regions in benign and malignant prostatic disease.

A modified silver stain technique for visualizing nucleolar organizer regions (AgNOR counting) was applied to 24 benign and 23 malignant prostatic biopsies. Marked inter-observer variation was found, particularly in sections with high AgNOR counts. After averaging the AgNOR counts of both observers, there was no significant difference in counts between the benign and the malignant biopsies. The AgNOR count appeared to be increased in tumours up to Gleason histological grade 6, but not in tumours of Gleason histological grade 7 or more.

Light microscopic, cytochemical and ultrastructural studies of a rat odontogenic epithelial cell line.

An odontogenic epithelial cell line, ROE-2B, was established by propagating disaggregated immature, unmineralized maxillary third molar tooth germs from 11-day old Sprague-Dawley rats on a feeder layer of Mitomycin-C treated NIH 3T3 embryonic mouse fibroblasts. The cell line has been maintained for more than 6 months and through 7 passages. Light microscopic examination of cells revealed colonies with epithelial morphology. Electron microscopic examination confirmed the epithelial nature by the demonstration of tonofilaments, desmosomes and basal lamina. Cells were also shown to have secretory vacuoles, an abundance of granular endoplasmic reticulum, free ribosomes, Golgi complex and mitochondria. Surface activity in the form of pseudopodia-like projections and micropinocytosis were noted. Epithelial cells forming keratin were demonstrated by a positive histochemical reaction with Rhodanile Blue. Immunohistochemical studies showed a positive reaction for CAM 5.2 indicating that the ROE-2B cells express the cytokeratins of simple or glandular epithelia. The ROE-2B cell line will be useful for studies on in vitro biological behaviour of odontogenic epithelial cells, and may allow the establishment of in vitro models of odontogenic tumours.

Epidermal growth factor receptor, nuclear proliferation antigen and interleukin-2 receptor expression in prostatic cancer.

Immunohistochemical methods have been used to study the relationship between epidermal growth factor receptor (EGF-R), T-lymphocyte infiltrate, interleukin-2 receptor (IL-2R) expression and the degree of cellular proliferation using the monoclonal antibody Ki-67. EGF-R was detected in only 2 out of the 19 malignant biopsies, but was present in the benign elements of all twelve of the heterogeneous biopsies examined. The level of immune response, as indicated by the percentage of T cells expressing the IL-2R, did not correlate with the expression of the nuclear proliferation antigen determined by Ki-67 monoclonal antibody staining intensity. This study fails to show a statistically significant correlation between the expression of EGF-R or nuclear proliferation antigen and the degree of the cell mediated immune response to the tumour.

Excision of residual masses after platinum based chemotherapy for non-seminomatous germ cell tumours.

Between January 1980 and June 1987, 42 patients receiving platinum based combination chemotherapy for advanced non-seminomatous germ cell tumours had residual masses, detected by computed tomography, after four or six treatment courses without tumour marker evidence of active disease. Resection of retroperitoneal (n = 32), pulmonary (n = 4) or thoracoabdominal (n = 2) disease revealed residual malignancy in nine patients (21%), differentiated teratoma in 14 (33%) and fibrosis or necrosis in 15 (36%). Laparotomy showed no evidence of a mass in four instances. Of the 42 patients, 14 had malignant teratoma undifferentiated in the primary tumour only one of whom (7%) had evidence of malignancy in the specimen resected post-chemotherapy. Conversely, six of 15 patients (40%) whose primary tumour was malignant teratoma intermediate had residual malignant tissue after treatment. With a median follow up of 36 months from post-chemotherapy surgery, 36 patients (86%) are continuously disease-free. Relapses occurred in one of nine patients with residual malignancy (11%), three of 14 with differentiated teratoma (21%), one of 15 with necrosis or fibrosis (7%) and in one patient who had a normal laparotomy. Four patients have died from their tumours, but two are currently disease-free following further surgery and chemotherapy for relapse. Neither primary nor post-chemotherapy histology was predictive of relapse, and although relapse was numerically more common in patients whose residual mass was incompletely excised (three of 12), this was not statistically significant.