Matti I. Kairaluoma

Immunohistochemical Study of Colorectal Tumors for Expression of a Novel Transmembrane Carbonic Anhydrase, MN/CA IX, with Potential Value as a Marker of Cell Proliferation

Carbonic anhydrase isoenzyme IX, MN/CA IX, is a recently discovered member of the carbonic anhydrase (CA) gene family with a suggested function in acid-base balance, intercellular communication, and cell proliferation. Increased expression of MN/CA IX has been observed with certain epithelial tumors. We investigated the expression of MN/CA IX in 69 colorectal neoplasms, consisting of 1 juvenile polyp, 8 hyperplastic polyps, 39 adenomatous lesions, 21 carcinomas, and 7 metastases. Tissue sections were immunostained with a monoclonal antibody specific to MN/CA IX. The proliferative activity of the tumor cells was evaluated by Ki-67 antigen immunoreactivity. The hyperplastic polyps showed a weak or moderate reaction for MN/CA IX only in the cryptal epithelium, as did the normal intestinal mucosa. The adenomas showed immunoreactivity mainly in the superficial part of the mucosa, whereas the distribution in the carcinomas and metastases was more diffuse. Comparative immunostaining of serial sections for Ki-67, a well established marker of cell proliferation, confirmed that MN/CA IX is expressed in areas with high proliferative capacity. Our results show abnormal MN/CA IX expression in colorectal neoplasms, suggesting its involvement in their pathogenesis. The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa.

Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms

BACKGROUND Seroepidemiologic studies have indicated an association between chronic Chlamydia pneumoniae infection and coronary heart disease. The organism, which is a common respiratory pathogen, has been demonstrated in atherosclerotic lesions of the aorta and coronary arteries. Abdominal aortic aneurysms are frequently associated with atherosclerosis, and inflammation may actually be an important factor in aneurysmal dilatation. Hence it could be assumed that C. pneumoniae may play a role in maintaining an inflammation and triggering the development of aortic aneurysms. METHODS AND RESULTS Specimens from abdominal aortic aneurysm were examined for the presence of C. pneumoniae by immunohistochemical analysis, the polymerase chain reaction amplifying omp 1 gene, transmission electron microscopy, and culture methods with histologically atherosclerosis-negative human aortic tissues used as a control group. Chlamydial lipopolysaccharide and C. pneumoniae specific antigens were found by immunohistochemistry in 12 and 8 of 12 aneurysm specimens, respectively, and C. pneumoniae DNA could be demonstrated in 6 of 6 aneurysm specimens studied. Furthermore electron microscopy revealed the presence of Chlamydia-like elementary bodies in three of four aneurysm specimens tested. None of the control samples gave positive reaction in the polymerase chain reaction, and C. pneumoniae antigens were not detected in any of them. CONCLUSIONS C. pneumoniae is frequently found in the vessel wall of abdominal aortic aneurysm. The potential etiopathogenetic role of C. pneumoniae in the development of these aneurysms remains to be studied.

Impact of Functional Results on Quality of Life After Rectal Cancer Surgery

PurposeQuality of life is an important outcome measure that has to be considered when deciding treatment strategy for rectal cancer. The aim of this study was to find out the impact of surgery-related adverse effects on quality of life.MethodsThe RAND-36 questionnaire and questionnaires assessing urinary, sexual, and bowel dysfunction were administered to 94 patients with no sign of recurrence a minimum of one year after curative surgery. Results were compared with age-matched and gender-matched general population.ResultsEighty-two (87 percent) patients answered the questionnaires. Major bowel dysfunction was as common after high anterior resection as after low anterior resection. Urinary complaints occurred as often after anterior resection as after abdominoperineal resection, but sexual dysfunction was more common after abdominoperineal resection. Overall, the patients reported better general health perception but poorer social functioning than population controls. In particular, elderly patients reported a significantly better quality of life in many dimensions than their population controls. There was no significant difference in quality of life between treatment groups. Major bowel dysfunction after anterior resection impaired social functioning compared with that of patients without such symptoms. Urinary dysfunction impaired social functioning and impotence impaired physical and social functioning.ConclusionsQuality of life after rectal cancer surgery is not worse than that of the general population. The major adverse impact of bowel and urogenital dysfunction is on social functioning. These adverse effects need to be discussed with the patient and preoperative function needs to be taken into account when choosing between treatment options. Permanent colostomy is not always the factor that disrupts a persons quality of life most.

Immunohistochemistry of Carbonic Anhydrase Isozyme IX (MN/CA IX) in Human Gut Reveals Polarized Expression in the Epithelial Cells with the Highest Proliferative Capacity

MN/CA IX is a recently discovered member of the carbonic anhydrase (CA) gene family that has been identified in the plasma membranes of certain tumor and epithelial cells and found to promote cell proliferation when transfected into NIH3T3 cells. This study presents localization of MN/CA IX in human gut and compares its distribution to those of CA I, II, and IV, which are known to be expressed in the intestinal epithelium. The specificity of the monoclonal antibody for MN/CA IX was confirmed by Western blots and immunostaining of COS-7 cells transfected with MN/CA IX cDNA. Immunohistochemical stainings of human gut revealed prominent polarized staining for MN/CA IX in the basolateral surfaces of the enterocytes of duodenum and jejunum, the reaction being most intense in the crypts. A moderate reaction was also seen in the crypts of ileal mucosa, whereas the staining became generally weaker in the large intestine. The results indicate isozyme-specific regulation of MN/CA IX expression along the cranial–caudal axis of the human gut and place the protein at the sites of rapid cell proliferation. The unique localization of MN/CA IX on the basolateral surfaces of proliferating crypt enterocytes suggests that it might serve as a ligand or a receptor for another protein that regulates intercellular communication or cell proliferation. Furthermore, MN/CA IX has a completely conserved active site domain of CAs suggesting that it could also participate in carbon dioxide/bicarbonate homeostasis.

Palliative operations for colorectal cancer

A review of 96 consecutive patients who underwent palliative surgery for primary colorectal cancer was undertaken to clarify the value of palliation achieved with surgical treatment. The overall rate of postoperative mortality was 8 percent (8 of 96) and the overall rate of postoperative morbidity was 24 percent (23 of 96). The mortality rate was 5 percent (3 of 66) after resective surgery and 17 percent (5 of 30) after nonresective surgery. Three deaths were related to the malignant disease, three were related to the intra-abdominal infection, and two were related to formation of intestinocutaneous fistulas. Of the 8 patients who died, 1 had a tumor with local visceral involvement only and 7 had a tumor with more distant spread. Median survival was 10 months for all patients, 15 months for patients treated with resective surgery, and 7 months for nonresected patients. Five patients (5 percent) have survived for longer than 5 years. The median relief of preoperative cancer symptoms was 4 months (4 months after resective surgery and 1 month after nonresective surgery). Twenty-five patients have undergone second surgery. It is concluded that palliative resective surgery for colorectal cancer can improve patient comfort with an acceptable postoperative mortality rate when cancer growth is localized and in favorable cases with more distant spread, whereas nonresective surgery fails to achieve symptom relief.

Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by measuring the concentration of the aminoterminal propeptide of type III procollagen in peripheral and aortal blood samples

PURPOSE The pathogenesis of abdominal aortic aneurysm (AAA) involves many factors; elastin degradation is believed to lead to initial dilation, whereas changes in the collagen structure predispose the aneurysm to rupture. The major collagens in the aortic wall are types I and III. We set out here to determine whether changes in serum propeptide of type III procollagen (PIIINP), a biologically relevant marker of type III collagen turnover, could be associated with the characteristics of AAA. METHODS The aminoterminal PIIINP and the carboxyterminal propeptide of type I collagen were measured by radioimmunoassay in 87 patients with AAA and 90 control subjects with aortodistal arteriosclerosis. The samples were taken from the peripheral blood and from the abdominal aorta at the levels of the diaphragm and the common iliac artery. RESULTS Mean PIIINP concentrations were higher in patients with AAA than in control subjects (3.47 micrograms/L vs 2.73 micrograms/L, p < 0.0001), correlating positively with aneurysm diameter in the former (r = 0.27, p = 0.04) and with the maximum thickness of the intraluminal thrombus (r = 0.39, p = 0.003). The gradient in PIIINP between the upper and lower end of the abdominal aorta was significant in the AAA group (-0.30 microgram/L, range -0.20 to -0.50 vs -0.10 micrograms/L, range -0.20 to 0.30, p = 0.002). CONCLUSIONS These studies indicate that the turnover of type III collagen is increased in patients with AAA.

Day-Case Stapled (Circular) vs. Diathermy Hemorrhoidectomy

AbstractPURPOSE: Stapled hemorrhoidectomy may be associated with less pain and faster recovery than conventional hemorrhoidectomy for prolapsing hemorrhoids. Therefore, the outcome of stapled hemorrhoidectomy was compared with that of diathermy hemorrhoidectomy in a randomized, controlled trial. METHODS: Sixty patients with third-degree hemorrhoids were randomly assigned to stapled hemorrhoidectomy (n = 30) or to diathermy hemorrhoidectomy in a day-case setting. Visual analog scale was used for postoperative pain scoring. Surgical and functional outcome was assessed at six weeks and one year after surgery. RESULTS: Operation time was a median of 21 (range, 11–59) minutes in the stapled group vs. 22 (range, 14–40) minutes in the diathermy group. Day-case surgery was successful in 24 patients (80 percent) in the stapled group vs. 29 patients (97 percent) in the diathermy group. Average pain in the stapled group was significantly lower than in the diathermy group (median, 1.8 (0.1–4.8) vs. 4.3 (1.4–6.2), 95 percent confidence interval difference medians, 1.15–3.85, P = 0.0002, Mann-Whitney U test) as was the average pain expected by the patients (median −2.7 (−0.15–0.8) vs. 0.006 (−4.05–0.5) respectively, 95 percent confidence interval difference medians, 0.5–3.55, P = 0.0018, Mann-Whitney U test). Postoperative morbidity and time off work were not significantly different between the diathermy and stapled groups. Seven treatment failures in the stapled group and one in the diathermy group necessitated other treatments at a later date. Patient satisfaction scores in the stapled and diathermy group were similar. Symptoms attributed to difficult rectal evacuation decreased significantly after surgery. CONCLUSIONS: Stapled hemorrhoidectomy is a significantly less painful operation than diathermy hemorrhoidectomy, but does not seem to offer significant advantages in terms of hospital stay or symptom control in the long term. Hemorrhoidectomy may improve symptoms of difficult rectal evacuation.

Percutaneous aspiration and alcohol sclerotherapy for symptomatic hepatic cysts. An alternative to surgical intervention.

Eight patients with 15 symptomatic nonneoplastic congenital hepatic cysts underwent ultrasound-guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. All cysts were treated at least twice at the same sitting. The volume of alcohol injected varied from 20 to 100 ml, depending on the size of the cyst. A cure was usually achieved with one alcohol sclerotherapy treatment. Only minor side effects such as transient pain and temperature elevation occurred. No recurrences were found during a follow-up period of 12 to 32 months. The results indicate that aspiration and alcohol sclerotherapy is a feasible alternative to surgical intervention in patients with symptomatic nonneoplastic congenital hepatic cysts. We recommend it as the treatment of choice in cases with high surgical risk or polycystic liver disease.

Synthesis of type I collagen in healing wounds in humans

To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays. The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test). On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached. Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing.

Treatment of Symptomatic Congenital Hepatic Cysts with Single-Session Percutaneous Drainage and Ethanol Sclerosis: Technique and Outcome

PURPOSE To evaluate the safety and efficacy of percutaneous aspiration and ethanol sclerotherapy as the sole treatment for symptomatic, nonneoplastic, congenital hepatic cysts. PATIENTS AND METHODS In a prospective study, 59 symptomatic, congenital hepatic cysts in 25 patients were treated with ultrasound-guided percutaneous aspiration and ethanol sclerotherapy. Eleven patients had a solitary cyst, and 14 patients had polycystic liver disease. Mean follow-up was 4 years. RESULTS Fifty-seven (97%) of 59 sclerotherapy procedures were technically successful, and there were no recurrences. Eight cysts in six patients disappeared totally. The mean diameter of the remaining 49 cysts decreased from 9 cm to 3 cm. At the last follow-up visit, 14 patients were asymptomatic, four had milder epigastric pain than before the treatment, and seven with polycystic liver disease had recurrent symptoms due to growth of nontreated cysts. No major complications occurred. CONCLUSION Percutaneous aspiration with ethanol sclerotherapy is a safe, effective, and minimally invasive treatment method for symptomatic congenital cysts. It is the initial treatment of choice for all patients with symptomatic congenital hepatic cysts.