Detection of colorectal neoplasia with peanut-agglutinin(PNA)-reactive carbohydrate structures in rectal mucus

In contrast to normal colorectal mucosa, peanut-agglutinin(PNA)-reactive glycoconjugates are commonly expressed in most colorectal carcinomas and in some pre-malignant conditions such as adenomas and ulcerative colitis. Since enzymatically detectable galactose-β1-3-N-acetyl-galactosamine residues are found in rectal mucus obtained from patients with carcinoma of the large bowel, it was investigated here whether PNA-reactive carbohydrate structures in rectal mucus can be exploited in the detection of colorectal neoplasia. Samples of rectal mucus obtained from 261 randomly selected patients with colorectal symptoms were applied on nitrocellulose filters. The presence of PNA-reactive glycoconjugates in mucus samples was determined by a peroxidase-conjugated PNA-overlay procedure. The results were correlated to findings from total colonoscopy/surgery and histopathology. PNA-reactive carbohydrate structures were detected in 76% of patients with carcinoma (p < 0.005), in 62% of patients with adenoma (p < 0.005), in 69% of patients with inflammatory bowel disease (p < 0.005), and in 38% of patients with hyperplastic polyps (NS), in contrast to 21% of the control subjects with macroscopically normal colorectal mucosa. These results show that PNA-reactive carbohydrate alterations in rectal mucus correlates with neoplastic and hyperproliferative conditions of the colorectal mucosa. The specificity of the PNA test for colorectal neoplasia was 76%. Therefore the use of more discriminate carbohydrate probes are needed for the pre-symptomatic detection of colorectal neoplasia. Int. J. Cancer 74:648–653, 1997.© 1997 Wiley-Liss, Inc.     

Experience of head and neck extracranial schwannomas in a whole population-based single-center patient series

Due to their rarity most of the literature concerning head and neck extracranial schwannomas consists of case reports and small patient series. The aim of the study was to describe population-based incidence, presenting signs and symptoms, management and outcome of head and neck extracranial schwannomas in a larger patient group. All the head and neck extracranial schwannoma patients managed during 1987–2008 at the Helsinki University Central Hospital with a referral area of 1.5 million inhabitants were searched. Altogether 47 patients were identified and subjected to retrospective chart review. Population-based incidence of head and neck extracranial schwannomas was 0.14/100,000/year. Eighty-eight percent of the patients had symptoms, which had lasted on average for 11.5 months prior to diagnosis. Presenting signs and symptoms were diverse depending on the affected nerve. Ninety-four percent of the patients were treated surgically. Sixty-four percent of the operations were macroscopically radical. The tumor capsule was intentionally left in place in 9 %. Surgery-related complications were detected in only 7 % of the patients, but 1 month postoperatively 52 % of them had symptoms, majority relating to different nerve deficits. Treatment of extracranial head and neck schwannomas remains challenging. The tumor is benign, and it grows slowly in a vast majority of cases, but its symptoms are highly variable. Correct timing of surgery is essential, as also patients who are preoperatively asymptomatic may suffer severe postoperative morbidity. Preoperative patient counseling needs to address the risks of neurological sequelae.     

Sentinel lymph node biopsy or elective neck dissection for patients with oral squamous cell carcinoma?

Sentinel lymph node biopsy (SNB) seems to be a promising method for staging clinically N0 neck in patients with oral squamous cell carcinoma (OSCC). In the present study, SNB was performed on 46 patients having elective neck dissection (END; six bilateral dissections) for T1–T3N0 OSCC. Sentinel lymph nodes (SLN) were first examined according to only slightly modified standard histopathologic protocol including sections at 1–2 mm intervals and H&E staining. SLN that appeared false negative (i.e. metastatic non-SLN without metastasis in a SLN) after the initial histopathologic examination were further assessed by step sectioning at 150 μm intervals and immunohistochemistry. Of the 47 neck sides with at least one SLN identified, nine contained metastasis in nine patients. After the initial histopathologic examination, SLNs were negative for malignant cells in four out of the nine metastatic neck sides. In one neck side, two metastatic SLNs were detected after the additional meticulous histopathologic work-up of the initially false negative SLNs. Therefore, in three neck sides the SLN did not contain metastasis although there was a metastasis in a non-SLN. In all these three cases with a false negative SLN, only one SLN had been identified. The sensitivity of the method (employing extensive histopathologic work-up) for detection of occult cervical metastasis was 67% (6/9 neck sides). The sensitivity of SNB for detection of occult metastasis seems to be poor in cases where only one SLN can be identified. The results of this study do not entitle us to entirely replace END by SNB in patients with OSCC.     

Multiple adenomas and synchronous hyperplastic polyps as predictors of metachronous colorectal adenomas

The development of metachronous adenomas was evaluated in 56 patients, 34 men and 22 women, with a history of 139 removed adenomas and non-neoplastic polyps, in order to determine whether the presence of concomitant adenomas and hyperplastic polyps at the initial examination could predict a higher risk of new adenomas. Sixteen of the 56 patients developed 21 metachronous adenomas and 1 rectal carcinoma after a median follow-up of 2.8 years. Among the 16 patients developing metachronous adenomas there were significantly more men (P less than 0.01), patients with multiple adenomas (P less than 0.05) or patients with adenomas and synchronous hyperplastic polyps at the initial examination (P = 0.043) than among the 40 patients without new adenomas. The combination of multiple adenomas with synchronous hyperplastic polyps at the initial examination predicted best the risk of developing new adenomas (P = 0.005). The results of the study suggest that patients with multiple adenomas and synchronous hyperplastic polyps at the initial examination may comprise a new higher risk group for developing metachronous colorectal adenomas.     

Involvement of plasma membrane enzymes in the proteolytic cleavage of luteinizing hormone receptor

In vitro degradation of LH receptor after occupancy by hCG was studied. Rat ovarian membranes labeled with [125I]iodo-hCG were incubated at 37 C; as a result, 30-40% of the radioactivity initially bound was rendered soluble in the medium. The molecular complexes in the medium and in incubated membranes solubilized with 1% Triton X-100 were then cross-linked with glutaraldehyde and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Particulate receptor-[125I]iodo-hCG complex exhibiting an apparent mol wt of 125,000 was cleaved during incubation into two distinct components (mol wt, 96,000 and 74,000) which appeared in the medium. Using tritiated hCG (beta-subunit labeled) instead of radioiodinated hCG (alpha-subunit labeled), these same two components were also observed, indicating that they both contain intact hCG (alpha and beta) as a part of their structure. In addition to the hormone (mol wt, 48,000), these two components contain receptor fragments with mol wt of 64,000 or 38,000, demonstrated directly by labeling the particulate receptor itself with periodate-tritiated borohydride before tagging with unlabeled hCG and in vitro incubation. These receptor fragments were purified from the medium by hCG-directed immunoaffinity chromatography and detached from the hormone by pH treatment. The intact receptor extracted from the membranes with detergent and purified identically in the absence of proteolysis migrated as a 90,000 mol wt polypeptide. These results demonstrate that after hormone occupancy, proteolytic cleavage of the 90,000 mol wt receptor polypeptide occurs at two specific sites. Thiol-blocking agents selectively prevented the appearance of the larger component (hCG coupled to 64,000 mol wt receptor fragment), while metal-chelating agents markedly decreased the appearance of the smaller component (hCG coupled to 38,000 mol wt receptor fragment) in the medium. Identical observations, obtained upon incubation of plasma membranes purified by sucrose density gradient centrifugation, suggest that plasma membrane enzymes are involved.     

Identification of glycoproteins expressing tumour-associated PNA-binding sites in colorectal carcinomas by SDS-GEL electrophoresis and PNA-labelling

Many tumour-specific antigens in gastrointestinal cancers have carbohydrate immuno-determinants. These epitopes can be identified by lectins and monoclonal antibodies. By using fluorescein-isothiocyanate (FITC)-conjugated peanut agglutinin (PNA) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we have investigated glycoproteins carrying altered carbohydrate epitopes in normal and carcinomatous human colorectal mucosa. In normal mucosa PNA stained goblet cell glycoconjugates in the supranuclear (Golgi) distribution. After neuraminidase pretreatment PNA stained actual mucin goblet itself at all levels of the crypts. Colorectal carcinomas displayed a strong and direct binding of PNA to apical cell membranes of carcinomatous cells and intraluminal secretions. Analysis of the glycoproteins by SDS-PAGE and PNA-labelling revealed four carcinoma-associated glycoproteins (26kD, 32kD, 35kD and 50kD). In addition, four glycoproteins (29kD, 30kD, 33kD and 36kD) common to normal and carcinomatous colorectal mucosa could be identified. All of these glycoproteins differed in their molecular weight from those in red cell controls which bind PNA only after desialylation. The study shows that the expression of PNA-binding sites in colorectal carcinomas signifies a cancer-associated carbohydrate alteration. Four carcinoma-associated glycoprotein antigens could be detected by this lectin. The antigens we have identified might be useful in the isolation and purification of more selective reagents for the serologic detection of colorectal cancer.     

Effect of temperature of insufflated CO2 during and after prolonged laparoscopic surgery

Background: Pneumoperitoneum with room temperature carbon dioxide (CO₂) has been shown to decrease core temperature and urine output. Methods: The effect of 37°C (warm) and room temperature (cool) CO₂ pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (>90 min). Results: The core temperature (p < 0.05) and cardiac index (p < 0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 ± 1.6 ml/kg/h) than during cool (0.9 ± 0.7 ml/kg/h) insufflation (p < 0.05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p < 0.05). Conclusions: Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function. Received: 23 June 1997/Accepted: 16 November 1997