Sucralfate versus placebo in treatment of non-ulcer dyspepsia.

One hundred fifty-one patients with non-ulcer dyspepsia, defined as chronic epigastric pain without concomitant symptoms of the irritable bowel syndrome and with no evidence of any organic disease other than macroscopic or microscopic gastritis/duodenitis seen at endoscopy on entry into the trial, were randomly assigned to treatment for four weeks with sucralfate or a placebo, 1 g three times a day one-half hour before meals, according to a double-blind model. Seventy-nine patients received sucralfate and 72 patients received a placebo. According to patients' subjective assessment of their symptoms at four weeks, 61 patients (77 percent) in the sucralfate group and 40 patients (56 percent) in the placebo group had become symptom-free or showed improvement, whereas the condition of 18 (23 percent) in the former group compared with 32 (44 percent) in the latter group remained unchanged or deteriorated. The difference between the groups was significant (p less than 0.01). The best response to sucralfate treatment (84 percent or more symptom-free or improved) was achieved in patients with mild or moderate symptoms and without macroscopic or microscopic inflammation of their gastric mucosa--a typical patient with non-ulcer dyspepsia. Our results indicate that sucralfate is significantly more effective than placebo in the treatment of non-ulcer dyspepsia.

High-activity carbonic anhydrase isoenzyme (CA II) in human gallbladder epithelium.

Acidification of bile is one of the factors that prevents calcium precipitation and thereby gallstone formation. Carbonic anhydrase II (CA II) has previously been shown to be one of the key factors in the human alimentary tract that regulates the acid-base balance. We demonstrated CA II expression in the human gallbladder epithelium using immunohistochemical techniques, elucidated the CA II content of the epithelium by digital image analysis of the immunohistochemically stained enzyme in samples from 16 patients undergoing cholecystectomy, and correlated the results with the calcium content of the gallstones. Nine patients had symptomatic gallstone disease and seven an acalculous, histologically normal gallbladder. The patients were classified into two groups on the basis of the calcium content of their gallstones: no gallstones or gallstones containing no calcium (Group 1) and gallstones with 2-87% calcium by weight (Group 2). The immunohistochemical techniques showed distinct epithelial CA II-positive staining in most of the gallbladder samples, but digital image analysis revealed distinct variations in staining intensity among them. The median staining intensity index was significantly higher in Group 1 (0.4463) than in Group 2 (0.2376; p = 0.0262). The results suggest that CA II is abundantly expressed in the normal gallbladder epithelium and that decreased expression may be associated with the formation of calcified gallstones. These findings are relevant to the pathogenesis of gallstone disease.

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.

Postpneumonectomy empyema in pulmonary carcinoma patients. Treatment with antibiotic irrigation and closed-chest drainage.

Seven patients with postpneumonectomy empyema who had had pulmonary carcinoma were treated with intrapleural antibiotic irrigation and closed-chest drainage. Two tubes were used to irrigate and drain the cavity. Although most patients had a bronchopleural or esophagopleural fistula, the treatment was successful in every case. Three of the 7 patients died of far-advanced carcinoma 1 to 2 years postoperatively, but none died of sequela of the empyema. In 3 patients with bronchopleural fistula, empyema recurred during the first postoperative year. However, it responded well to repeated irrigation and drainage. This simple, time-saving, and easily repeatable regimen proved to be both effective and also very comfortable for the patient. It has none of the disadvantages of open thoracic drainage or mutilating thoracoplasty.

A simple cannulation technique for perfusion problems in advanced aortic dissection.

A simplified left atrial-distal aorta bypass for operative treatment of extensive dissecting. Type III, aneurysms of the distal thoracic aorta is reported. In this technique the lower part of the body is perfused through a large cannula placed into the true lumen of the several distal aorta. The indications and advantages of the method are discussed.

Celestin tube palliation of unresectable esophageal carcinoma.

Celestin tube intubation was performed in 108 patients with unresectable carcinoma of the esophagus and cardia, in 83 per cent as the initial operation and in 17 per cent after exploration. The hospital mortality rate was 16 per cent, including a 7.4 per cent mortality rate from technical causes. The most frequent causes of death were perforations of the esophagus and cardia and aspiration pneumonia. Nonfatal complications occurred in 13 per cent of surviving patients, obstruction and dislodgment of the tube being the most common. All patients were able to swallow at discharge, and 91 per cent of them could take food by mouth until the time of death. In 9 per cent, additional palliation, usually esophagoscopy or gastrostomy, was required. Ninety-one patients survived one to 21 months (average 5.8 months). The 6 month survival rate was 44 per cent and the one-year survival 9 per cent.

Intraoperative hemodynamic evaluation of the Björk-Shiley tilting disc aortic valve.

Intraoperative cardiac output and aortic and left ventricular pressures were measured simultaneously in 15 consecutive patients before and after aortic valve replacement (AVR) with the Björk-Shiley tilting disc valve. The predominant lesion in these patients was aortic stenosis. The following hemodynamic indices were calculated: aortic valve area (AVA), determined by Gorlin's formula, effective orifice area, and effective area index. Their applicability as hemodynamic criteria of the immediate hemodynamic performance of the replaced valve is discussed. By every criterion, AVR greatly improved the hemodynamic performance. The effective area index seemed more suitable than the other indices for the intraoperative hemodynamic evaluation of the replaced aortic valve.

Myocardial reactive hyperemia caused by initial myocardial anoxia during aortic valve replacement.

Reactive hyperemic response of individual coronary arteries and of the whole heart to anoxia during coronary cannulation was investigated in 10 patients undergoing aortic valve replacement. Reactive hyperemic response in man is identical to that reported in experimental investigations. The duration of hyperemic response was dependent on the length of the preceding period of anoxia; the longer the period of anoxia, the more prolonged was the hyperemic response. No significant collateral circulation between the coronary arteries could be demonstrated during prolonged anoxia of an individual coronary artery. Blood flow debt was almost always overpaid, but the repayment percentage decreased with the lengthening of the anoxic period, being 460 percent after a short period of anoxia (less than or equal to 2 minutes), 230 percent after an anoxic period of moderate length (3 to 5 minutes), and only 160 percent after a long period of anoxia (greater than or equal to 7 minutes). The total mean repayment of blood flow debt of the whole heart was 195 percent.

Aminoterminal propeptide of type III procollagen in serum during wound healing in human beings.

The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum as an indicator of tissue repair was studied in 71 surgical patients undergoing minor, moderate abdominal, major abdominal, or hip surgery. An increase in serum PIIINP concentrations took place within the first week, and its magnitude was related to the extent of the soft-tissue operations. After the hip replacement, the maximum PIIINP concentration was reached somewhat later. Very high levels of serum PIIINP were seen in three patients with serious wound infections. The serum PIIINP antigenicity consisted both before and after surgery of equal proportions of two forms, one corresponding to the propeptide as set free during synthesis of new collagen and the other being larger and probably derived from turnover of type III collagen fibers. The proportion of the latter form was accentuated in infection. In contrast, in the wound the form derived from synthesis of type III collagen predominated. These results suggest that the postoperative increase in serum PIIINP levels is partly the result of tissue repair and partly the result of whole-body turnover of type III collagen.

Nontraumatic perforations of the small intestine.

The etiology of nontraumatic small bowel perforations in 24 operated patients was as follows: strangulation in five, diverticulum in four, foreign bodies in four, idiopathic in three, Crogn's disease in two, malignant atrophic papulosis of Degos (MAP) in two, and tuberculosis, carcinoid tumor, radiotherapy, and iatrogenic in one. The high mortality rate in these patients appeared to be a funciton of the disease process rather than of the means of treatment. In favorable circumstances, as in strictly localized lesions with well known etiology and otherwise normal bowel, a simple closure of perforation is warranted. In more far advanced cases operated upon early enough, we still consider bowel resection and primary anastomosis as the best method of treatment, though it yielded poor results in procedures are advisable to protect the anastomosis.

Surgical treatment of recurrent colorectal cancer. Five-year follow-up.

Analysis of 81 consecutive patients with recurrent colorectal cancer was undertaken to evaluate the rationale and efficacy of surgical re-treatment. The disease-free interval after primary surgery and the diagnostic delay did not clearly differ between the modes of recurrences. Symptoms preceded the diagnosis of recurrence in 73% (59) of the cases, with pain being the most frequent symptom (n = 22). Of the patients, 58% (47) underwent reoperations, 38% (31) underwent reresections, and 10% (8) underwent radical resections. The overall postoperative mortality was 13%, and the postoperative morbidity was 45%. The postoperative relief of cancer symptoms after resective surgery was 8 months and, after nonresective surgery, 2 months. The median survival was 24 months for patients who underwent resections, 8 months for patients who were treated by nonresective surgery, and 15 months for patients who were treated conservatively. Radical resection clearly prolonged survival when compared with palliative resections and nonresective procedures. On the basis of these results, it was concluded that resective surgery, when possible, can improve survival and patient comfort after recurrence of colorectal cancer.

Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial.

OBJECTIVE: To determine whether an intensified follow-up of patients with colorectal cancer can lead to improved reresectability and a better long-term survival. DESIGN: A prospective randomized trial of 106 patients. SETTING: Oulu University Hospital, a referral center in northern Finland. PATIENTS: A total of 106 consecutive patients who underwent radical resection for colorectal cancer, 54 of whom were randomized into a conventional follow-up group and 52 into an intensified follow-up group. MAIN OUTCOME MEASURES: After a 5-year follow-up, the time of detection of recurrence, the recurrence rates, the first method showing recurrence, the mode of recurrence, reresectability, and survival were compared between the groups. RESULTS: The recurrences were identified earlier in the intensified follow-up group than in the conventional follow-up group (mean +/- SD, 10 +/- 5 months vs 15 +/- 10 months). The overall recurrence rate was 41%, with 39% in the conventional group and 42% in the intensified group. Carcinoembryonic antigen determination was the most common method showing recurrence in both groups. Endoscopy and ultrasound were beneficial in the intensified follow-up group, but computed tomography failed to improve the diagnostics. The mode of recurrence did not differ between the groups. Radical resections were performed on 19% (8/43) of the patients, 14% (3/21) in the conventional group and 22% (5/22) in the intensified group. The cumulative 5-year survival was 54% in the conventional group and 59% in the intensified group. CONCLUSION: Earlier detection of recurrent colorectal cancer by intensified follow-up does not lead to either significantly increased reresectability or improved 5-year survival.

Mediastinal window: a cause of simultaneous bilateral spontaneous pneumothorax.

A case of bilateral spontaneous pneumothorax with critical collapse of both lungs in a previously healthy 19-year-old woman is described. A congenital defect of mediastinal septum was suspected on the basis of roentgenographic findings and confirmed by right-sided thoracotomy. This mediastinal window between the pleural spaces allowed air leaking from a ruptured right lung apical bulla to collapse not only the right lung but also the left. Apical TA stapler resection and right-sided parietal pleurectomy was performed to prevent recurrence.

Calcium microemboli and microfilters in valve operations.

Fatal microemboli occurred in 3 of 100 consecutive patients having aortic valve replacement; 2 occurred during perfusion before the microfilter era, and 1 occurred intraoperatively despite the use of in-line filters. In all 3 patients cerebral symptoms were present immediately postoperatively, and each died of severe brain damage. On postmortem examination cerebral calcium microemboli were verified in only 2 patients, although the brain of each patient contained minute infarctions. However, calcium particles were found in the kidneys of all 3 patients. Thus the kidneys proved to be the best place for detection of calcium emboli on postmortem examination. Although the microfilters currently available effectively prevent microemboli during extracorporeal circulation, the surgeon should be aware that embolization can also occur immediately after discontinuation of perfusion. The means of protecting the patient from this are discussed.

Intraoperative changes in coronary resistance during aortic valve replacement.

Coronary vascular resistance was investigated in 10 patients undergoing aortic valve replacement using continuous constant-pressure coronary perfusion at 32 degrees C. After coronary flow was initiated, resistance was low but increased steadily until it reached a certain resting level. The plateau was attained faster after a short period of anoxia than after a longer period. The initial postischemic resistance was dependent on the duration preceding anoxia, being of the same magnitude after short and moderate periods of anoxia but significantly higher after a long period. This resistance difference between the groups lasted for the whole perfusion. The total coronary resistance and flow reached a plateau in 30 minutes, while resistance increased threefold but flow decreased to half of the initial postanoxia flow. Our results indicate the importance of initiating coronary perfusion soon after aortic cross-clamping to avoid increase in the initial vascular resistance and subsequent inadequate myocardial flow.

Pharmacokinetics of ftorafur after intravenous and oral administration.

The pharmacokinetics of ftorafur (FT), an antineoplastic agent, has been studied in seven cancer patients by determining concentrations of the unchanged compound in serum after single IV and PO doses of 2 g FT. Serum drug concentrations were determined by a new quantitative thin-layer chromatographic method. After IV administration, the mean half-lives of the distribution phase and elimination phase were 1.0 h and 7.6 h, respectively. Total serum clearance was 69 ml/h . kg and the apparent volume of distribution was 0.66 l/kg. Following PO administration there was a short lag-time, 11 min, before the appearance of FT in peripheral serum, and the maximum concentration in peripheral serum was achieved in 3.2 h. Oral absorption was complete and no significant first-pass metabolism could be observed. FT elimination, measured in serum taken from the portal vein and a peripheral vein, occurred substantially at the same rate after IV and PO administration. In contrast, after the PO dose FT appeared in the portal serum significantly earlier than in the peripheral serum, resulting in a difference of 1.7 h in the time of maximum serum concentration. This indicates fast gastrointestinal absorption of FT but hepatic retention (without metabolism) before the appearance of FT in the peripheral serum.

Staplers in palliative bypass surgery for unresectable pancreatic cancer.

To assess the role of stapling devices and routine gastroenterostomy in palliative bypass surgery, the hospital records of 150 consecutive patients with unresectable, histologically proven pancreatic adenocarcinoma requiring palliative bypass procedure were reviewed. During recent years staplers have gained increasing acceptance for construction of palliative anastomoses. Mortality and morbidity were lower after stapled anastomoses. The use of staplers for construction of double bypass reduced the operation time by 45 min (p less than 0.001). After initial biliary diversion 6% of the patients required later reoperation for gastric outlet obstruction. Routine gastroenterostomy made reoperation unnecessary. Delayed gastric emptying occurred, however, in 10% and significant upper gastrointestinal bleeding in 7% of the patients after prophylactic gastroenterostomy. We conclude that stapling devices are safe and practical in palliative bypass surgery and they significantly reduce operation time if more than one bypass is required. The relatively high incidence of delayed gastric emptying, and significant upper gastrointestinal bleeding after prophylactic gastroenterostomy and the infrequent occurrence of gastric outlet obstruction after initial biliary bypass together with the low mortality after reoperation, suggest that gastroenterostomy should be performed on a selective basis only.

Superselective intra-arterial chemotherapy with mitomycin C for hepatocellular carcinoma.

Thirty-six patients with primary hepatocellular carcinoma were treated by superselective intra-arterial chemotherapy with mitomycin C (SIAC) between 1981 and 1990, either as primary chemotherapy without operation (28) or as additional therapy after resective surgery (8). During the same period 10 patients were resected radically and 26 patients treated conservatively. The overall response rate to SIAC was 25% (9/36), comprising two complete and seven partial responses. The cumulative 5-year survival rate was significantly related to the percentage of hepatic replacement (PHR) (P < 0.01) and to resective surgery (P < 0.01). Overall 5-year survival was only 4% and all the patients with PHR over 75% died within 2 or 3 years. Cessation of chemotherapy was necessary in 72% of cases (26/36), because of tumour progression in 20 cases, chemotherapy toxicity in four and one technical error in one and patient refusal in one. The results of the use of SIAC as a chemotherapeutic agent for hepatocellular cancer may be regarded as disappointing, as the response rate remained low and the medication was unable to prevent tumour progression in most cases. We intend to use SIAC only for stage I-II tumours and as additional therapy after surgery when the radicality remains uncertain.

Early results of follow-up after radical resection for colorectal cancer. Preliminary results of a prospective randomized trial.

One-hundred and six consecutive patients were included in a prospective study of intensive monitoring after radical resection for colorectal cancer, 54 being randomized into a conventional follow-up group (Group I) and 52 into an intensified follow-up group (Group II). After a median follow-up of 2 years the overall rate of detection recurrence in Group I was 24% (13/54) and in Group II 25% (13/52). The recurrence rates among those followed up for at least 2 years were 36% (10/28) and 30% (9/30), respectively. Of the recurrences in Group I, one was local, five regional and six distant, and the corresponding figures in Group II were three, four and five. One radical extirpation of a local perineal recurrence has been performed in Group I, whereas two intestinal reresections for local anastomotic recurrences and two hepatic resections for solitary hepatic metastases have been performed in Group II. Mortality to date is 13% (7/54) in Group I and 8% (4/52) in Group II. Two adenomatous polyps have been removed from the colon in Group I during endoscopic surveillance and seven in Group II. These preliminary results encourage us to continue the trial up to 5 years after primary surgery.

Adenocarcinoma of the gastric cardia.

One hundred and ninety-five patients operated on for adenocarcinoma of the gastric cardia during the years 1961-90 were analysed and the present data indicate that the more enthusiastic attitude adopted towards resective surgery led to a significant increase in operative explorations performed and in resectability rate, from 50% (44/88) and 35% (28/88) during the years 1961-75 to 84% (90/107) and 56% (60/107) during the years 1976-90, respectively. The difference between radical resections, 54% (15/28) and 67% (34/60), remained non-significant. The overall postoperative mortality and morbidity after resective surgery were 14% and 35% and these rates did not rise with time. The anastomotic leakage rate was 15%. Anastomotic leakage was, in fact, not only the most common postoperative complication but also the most common cause of death. Overall cumulative survivals at 1, 3 and 5 years were 47%, 11% and 5%. Comparison of the cumulative survival rates between the 15-year periods indicated that there were no differences in overall survival or in survival after resective surgery. We regard these results disappointing, because over half of the patients died in 1 year and because the long-term survival remained dismal.