Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers.

OBJECTIVES: The majority of solid human malignancies demonstrate DNA aneuploidy as a consequence of chromosomal instability. We wanted to investigate whether Aurora A, Aurora B, BUB1B and Mad2 were associated with the development of aneuploidy in colorectal adenocarcinomas as suggested by several in vitro studies, and if their protein levels were related to alterations at the corresponding chromosomal loci. MATERIALS AND METHODS: Expression levels of these spindle proteins were investigated by immunohistochemistry using tissue micro-arrays in a series of DNA aneuploid and diploid colorectal adenocarcinomas previously examined for genomic aberrations by comparative genomic hybridization. RESULTS: All proteins were overexpressed in malignant tissues compared to controls (P < 0.001 for all). BUB1B level was significantly reduced in aneuploid compared to diploid cancers (P = 0.001), whereas expression of the other proteins was not associated with DNA ploidy status. High levels of Aurora A (P = 0.049) and low levels of Aurora B (P = 0.031) were associated with poor prognosis, but no associations were revealed between protein expression and genomic aberration. CONCLUSIONS: A significant reduction of BUB1B level was detected in aneuploid compared to diploid colorectal cancers, consistent with earlier studies showing that loss of spindle checkpoint function may be involved in development of DNA aneuploidy. Our data also show that spindle proteins are overexpressed in colorectal cancers, and that expression of the Aurora kinases is associated with prognosis in colorectal cancer.

Outpatient laparoscopic surgery: feasibility and consequences for education and health care costs.

BACKGROUND: The purpose of this paper is to describe the outcome of ambulatory laparoscopic cholecystectomy (LC), antireflux surgery, adrenalectomy and splenectomy and possible implications for surgical education and health care costs. METHODS: Prospective, observational study 1994-2003. RESULTS: The success rate of ambulatory treatment was 83.5% in 1060 LC patients, 80% in 113 antireflux procedures, 100% in 22 laparoscopic adrenalectomies, and 75% in 12 laparoscopic splenectomies. In a total number of 1207 patients, health care costs were reduced by almost 700,000 dollars, compared to 1-day hospital stay. The educational potential of same-day surgery is large, due to high numbers of patients, and 80% of our educational potential has been exploited. CONCLUSION: Ambulatory laparoscopic surgery is cost effective, patient friendly, and appropriate for surgical resident training. Strict organization of security rules is mandatory.

Regional cerebral blood flow in patients with primary hyperparathyroidism before and after successful parathyroidectomy.

BACKGROUND: Single-photon emission computed tomography (SPECT) is used to study cerebral blood flow and cerebral metabolism in various neuropsychiatric disorders. Reduced regional cerebral blood flow has been demonstrated in patients with depression and chronic fatigue, symptoms that are common in primary hyperparathyroidism. The aim of this study was to reveal possible changes in regional cerebral blood flow in patients with primary hyperparathyroidism before and after operative treatment. METHODS: This was a prospective study of regional cerebral blood flow in 16 consecutive women of median age 72 (range 50-82) years using SPECT with (99m)Tc-labelled hexamethylpropylenamine-oxime. The measurements were performed before and 2, 4 and 12 months after parathyroidectomy. The Montgomery and Asberg depression rating scale (MADRS) depression score was used as a parallel clinical test. RESULTS: Reduced (pathological) regional cerebral blood flow was seen before operation in 14 patients, 13 with a solitary adenoma and one with double adenoma. After surgery, this improved to normal values in 13, but was further reduced in one. In two patients with preoperative normal regional cerebral blood flow, both of whom were asymptomatic and had diffuse hyperplasia, a slight reduction was demonstrated. Eight patients had a pathological preoperative MADRS score, which normalized in seven after surgical treatment. CONCLUSION: The finding of reduced regional cerebral blood flow in patients with primary hyperparathyroidism followed by significant improvement after operation might influence the case for surgical treatment.

Prognostic significance of recurrent chromosomal aberrations detected by comparative genomic hybridization in sporadic colorectal cancer.

Colorectal carcinomas are characterized by frequent recurrent gains and losses of chromosomal material, especially gains of chromosome arms 20q and 13q, and losses of chromosome arms 18q and 4q. These may be important in the development and progression of colorectal carcinomas. Chromosomal aberrations detected by comparative genomic hybridization in 67 sporadic colorectal carcinomas were examined for their possible associations with patient survival. Dukes' stage, tumor DNA ploidy status, and TP53 genotype/phenotype were also examined for the same. Patients with losses of chromosomal arms 1p, 4q, 8p, 14q, or 18q or gain of chromosomal arm 20q had significantly shorter survival times than those without these aberrations (univariate relative risk 3.45, 2.71, 3.32, 3.26, 3.32, 3.91, respectively), as did patients with more than six chromosomal aberrations per tumor than those with fewer than six aberrations (univariate relative risk 3.26, P = 0.013). DNA aneuploidy and Dukes' stage C + D resulted in poor patient survival (univariate relative risk 3.58, 3.39, respectively). Dukes' stage C + D, 1p loss and 8p loss emerged as the only independent prognostic parameters (relative risk 3.22, 2.53, 2.45, respectively) when entered into multivariate survival analysis together with other significant parameters from univariate survival analysis. Loss of chromosome arm 1p, 4q, 8p, 14q, or 18q or gain of chromosome arm 20q thus results in shortened survival times in colorectal cancer patients. 1p loss and 8p loss were shown to be independent predictors of poor prognosis.

[Hernia surgery in Norway]. / Lyskebrokkirurgi i Norge.

BACKGROUND: Inguinal hernia repair has undergone major changes during the last decade. This study aimed to explore the impact on treatment algorithms used in Norway. METHODS: A questionnaire was sent to all public hospitals in January 1999. RESULTS: 57 of 58 hospitals where inguinal hernia repairs were undertaken responded. Most repairs are undertaken in local/district hospitals, but in the majority of hospitals, surgeons performed a limited number of procedures (one or two per month). The vast majority of hospitals used two different surgical techniques, open mesh techniques being the preferred technique. Most hospitals made limited use of laparoscopic techniques. Sick-leave periods were shorter after surgery with open mesh techniques as compared to traditional techniques. Less than 20% of hospitals had established control regimens. INTERPRETATION: A clear tendency towards standardization of inguinal hernia repair can be observed throughout the country. Open mesh techniques have now replaced the traditional operative methods, whereas laparoscopic technique has not been adopted. Quality assessment of inguinal hernia repair could be improved.

Day-case laparoscopic fundoplication for gastro-oesophageal reflux disease.

BACKGROUND: Based on a series of successful outpatient laparoscopic cholecystectomies, day-case laparoscopic fundoplication for gastro-oesophageal reflux disease was introduced in January 1997. The initial results are reported. METHODS: Inclusion criteria were American Society of Anesthesiologists grade I-II, living within 30 min travel from the hospital, and adult company at home. Initially only selected patients were offered day-case treatment, but later it was adopted as routine. The patients underwent general intravenous anaesthesia with propofol and remifentanil, and were given ketorolac, propacetamol, droperidol and ondansetron as prophylaxis against postoperative pain and nausea. The surgical procedure was Nissen-Rosetti fundoplication or semifundoplication depending on oesophageal manometric results. RESULTS: Forty-five patients were included. Four patients were admitted; 41 were discharged as planned 3-8 h after operation, and five of these patients were readmitted. One underwent reoperation for necrosis of the gastric fundus. A further five patients visited the outpatient department without need for admission. At follow-up 31 patients were satisfied with the day-case treatment, five were indifferent, and five were dissatisfied because of pain. If offered a similar operation in the future, 26 patients would have preferred and seven would have accepted day-case treatment, and eight would not. CONCLUSION: Outpatient laparoscopic fundoplication is safe and well tolerated by the majority of patients.

Severe pancreatitis after parathyroidectomy.

Cope showed in 1957 that pancreatitis may be the presenting symptom in hyperparathyroidism. Since then, the literature has reported a coincidence of primary hyperparathyroidism and pancreatitis between 1% and 19%, but the true relationship has not been fully established. When severe pancreatitis follows parathyroidectomy, a condition familiar to parathyroid surgeons, reports are mostly anecdotal and by many authors considered to be coincidental. We present the case history of a 58-year-old man with a longstanding history of untreated primary hyperparathyroidism who developed severe pancreatitis immediately after removal of a 400-mg parathyroid adenoma. He was the first in a series of 108 operated patients to develop this complication. His preoperative levels of parathormone and serum calcium were the highest in our material. We believe that pancreatitis after parathyroidectomy is a real but rare complication that might be predicted by preoperative high values of serum calcium and parathormone.

[Traditional surgery of inguinal hernia]. / Lyskebrokkirurgi på gammelt vis.

Inguinal hernia repair is associated with a variety of complications of which the recurrence rate is one of the most important. The aim of this study was to examine all patients one year after surgery for inguinal hernia in an outpatient clinic. 12 months after the operation patients were interviewed and physically examined. 172 hernias in 166 patients were repaired in 1996 in our outpatient unit. 17 surgeons used nine different techniques. Follow-up was achieved in 93.9% of patients alive. Ten recurrences were found (6.3%). Four of the patients were not aware of their recurrence. 11% of the patients still had discomfort or pain after twelve months, whereas 5.2% had not resumed full activity. Other complications occurred in more than 20% of the operations. A "free to do policy" in inguinal hernia repair results in high recurrence and complication rates even in the hands of experienced surgeons in our clinic. The present study shows that an interview as well as a physical examination are necessary in evaluating recurrences, postoperative complications, postoperative pain and time to full mobilisation. Without physical examination, the recurrence rate would have been underreported.

Standard preoperative assessment can improve outcome after cholecystectomy.

OBJECTIVE: To assess the outcome of cholecystectomy after standard preoperative handling and selection of patients, focusing on the potential of the operation to eliminate biliary colic. DESIGN: Prospective study. SETTING: University Hospital, Norway. PATIENTS: 806 patients (median age 56, range 18-91 years, male:female ratio 1:2.7), were referred to our clinic for cholecystectomy between 1992 and 1996. INTERVENTIONS: Unless there was a clear indication for cholecystectomy (frequent attacks of biliary colic/or recent complications of gallstones or both), patients were investigated in a standard way to find out what else was causing the abdominal pain. MAIN OUTCOME MEASURES: Residual pain was assessed at a clinical examination three months postoperatively, and clinical condition a median of three years later was assessed by a questionnaire. RESULTS: 465 (58%) patients were operated on primarily, and an additional 29 patients were operated on after further evaluation. Three months after cholecystectomy, 35 (7%) had persistent pain, mostly caused by other specific diseases and relieved after specific treatment. A median 3 years postoperatively, only 21 (4%) reported that they still had abdominal pain. CONCLUSION: Standard selection of patient improved the outcome of cholecystectomy. Compared with a historical control group, residual pain after three months was reduced from 20% to 7%. After three years, 96% of the patients no longer had their main clinical problem.

[Primary hyperparathyroidism--a 16-year material from a central hospital]. / Primaer hyperparatyreoidisme--et 16-årsmateriale fra et sentralsykehus.

BACKGROUND: In Norway, population 4.3 million, approximately 160 patients a year have undergone surgery for primary hyperparathyroidism during the last ten years. Previous reports are rare. MATERIAL AND METHODS: A retrospective analysis of all patients operated for primary hyperparathyroidism during 16 years at Vestfold Hospital, which serves a population of 200,000. Late recurrences and persisting hypocalcaemia were evaluated with laboratory tests median eight years after surgery. RESULTS: 104 patients were operated (88 females and 16 males; median age 64 years, range 22-78). Adenomas were found in 88 patients, of which four had double adenomas, and hyperplasia in 16 patients. Three patients died postoperatively, within 30 days, all of them high-risk patients. Two patients were reoperated because of bleeding. In one patient an infection was drained. Median hospital stay was five days. Two patients had persisting hypercalcaemia; eight patients needed permanent vitamin D substitution. Four recurrences were detected. Normocalcaemia was achieved in 91 patients (90%). INTERPRETATION: Surgical treatment leads to normocalcemia in 90% of patient, but is not risk-free in severely ill patients. To assess the true benefit of the operation for the individual patient, better preoperative mapping of symptoms and better follow-up protocols should be implemented.

Cholecystectomy rates, gallstone prevalence, and handling of bile duct injuries in Scandinavia. A comparative audit.

BACKGROUND: This study was performed to assess three fields of surgical decision making: (a) selecting patients for cholecystectomy, (b) analyzing the value of intraoperative cholangiography (IOC), and (c) surveying the handling of bile duct (BD) injuries. METHODS: Yearly numbers of laparoscopic (LC) and open cholecystectomies (OC) were collected from official health care statistics. Data concerning handling of BD injuries were taken from each country's LC registry. RESULTS: From 1989 to 1995 the median cholecystectomy rate was 6.82 per 10,000 inhabitants in Denmark, 14.20 in Finland, 6.23 in Norway, and 12.17 in Sweden. Deviations from the median yearly rates in each country were -14.8% to +14.4%. Repair of BD injury was performed in the same local hospital where the injury had occurred in 68-98% of cases. CONCLUSIONS: Patient selection differed between countries before the introduction of LC, and these differences have persisted. Few patients with BD injury were treated in referral centers.

A population-based survey of biliary surgery in Norway. Relationship between patient volume and quality of surgical treatment.

BACKGROUND: A registry was initiated in order to establish national standards for the quality of surgical treatment of gallstones, and to provide feedback to all hospitals about serious complications, in order to reduce their future incidence. METHODS: Prospective registration of complications was performed at all hospitals and collected in the National Norwegian Cholecystectomy Registry (NNCR) over a period of 33 months. RESULTS: Open cholecystectomy (OC) was performed in 1011 patients, and laparoscopic cholecystectomy (LC) in 4332 patients. These figures represent 68% of all procedures performed nationally. The frequency of bile duct (BD) injury was 0. 8% for LC versus 0.7% for OC (ns); mortality was 0.1% versus 2.1%, respectively (p < 0.05). The frequency of BD injury and mortality were added; the sum comprised the Severe Complication Index (SCI). A linear relationship was found between SCI and patient volume (correlation coefficient, r22 = 0.78). CONCLUSIONS: SCI was found to be the best indicator of surgical success. We have proposed its use as a parameter for a future prospective quality assurance program, along with patient volume.

Desflurane versus propofol maintenance for outpatient laparoscopic cholecystectomy.

BACKGROUND: The aims of the study were to evaluate costs and clinical characteristics of desflurane-based anaesthetic maintenance versus propofol for outpatient cholecystectomy. METHODS: All 60 patients received ketamine 0.2 mg kg(-1), fentanyl 2 microg kg(-1) and propofol 2 mg kg(-1) for induction. Ketorolac 0.4 mg kg(-1) and ondansetron 0.05 mg kg(-1) +droperidol 20 microg kg(-1) was given as prophylaxis for postoperative pain and emesis, respectively. The patients were randomly assigned into Group P with propofol maintenance and opioid supplements, or Group D with desflurane in a low-flow circuit system. RESULTS: All the patients were successfully discharged within 8 h without any serious complications. Emergence from anaesthesia was more rapid after desflurane; they opened their eyes and stated date of birth at mean 6.4 and 8.4 min respectively, compared with 9.6 and 12 min in the propofol group (P<0.05). Nausea and pain were more frequent in Group D, 40% and 80% respectively; versus 17% and 50% in Group P (P<0.05). By telephone interview at 24 h and 7 d after the procedure, there was no major difference between the groups. With desflurane, drug costs per case were 10 $ lower than with propofol. CONCLUSION: We conclude that desflurane is cheaper and has a more rapid emergence than propofol for outpatient cholecystectomy. However, propofol results in less pain and nausea in the recovery unit. Despite ondansetron and droperidol prophylaxis, there was still a substantial amount of nausea and vomiting after desflurane.

Outpatient laparoscopic cholecystectomy.

INTRODUCTION: The results of laparoscopic cholecystectomy performed as an outpatient procedure were evaluated in a prospective study. METHODS: Initially, only well motivated and healthy patients were offered outpatient laparoscopic cholecystectomy. After 50 procedures, all patients referred to the hospital, except those with American Society of Anesthesiologists (ASA) grade IV and those living alone, were included. Some 200 procedures were studied. RESULTS: Twelve patients (6 per cent) were admitted, and 188 (94 per cent) were discharged 4-8 h after operation. Fifteen patients (8 per cent) who had early discharge were readmitted, nine with complications; in six no complications were documented. The frequency of minor complications was 2 per cent and of major complications 5 per cent. Some 173 patients who had successful outpatient laparoscopic cholecystectomy completed a questionnaire: 164 (95 per cent) characterized their experience as excellent, five (3 per cent) as good, two (1 per cent) as intermediate and two (1 per cent) as unacceptable. DISCUSSION: This high achievement of day-case treatment, even in patients with ASA grade III, is explained by a new anaesthetic regimen together with good surgical technique and close follow-up.

Complications in laparoscopic and open cholecystectomy: a prospective comparative trial.

Laparoscopic cholecystectomy (n = 250) was compared with the open procedure (n = 250) in a prospective comparative study focusing on complications. Severity grade was classified according to the Toronto system. The frequency of severity grade 1 complications was equal after open and laparoscopic cholecystectomy (5.6%), but major complications (grade 2 and higher) were significantly more frequent in the open group (10.4 versus 3.6%). The only postoperative death occurred after open cholecystectomy. The conventional advantages of laparoscopic cholecystectomy were also verified: The need for postoperative analgesics was significantly reduced from 7 (range, 4-16) standard opiate doses in the open group to 3 (range, 0-7) in the laparoscopic group. Hospital stay was reduced from 6 (range, 4-31) days after open surgery to 2 (range, 1-7) days after laparoscopic surgery and sick leave from 28 (range, 18-48) to 10 (range, 2-21) days, respectively. The overall complication rate was significantly higher in the open group (16 versus 9%, p < 0.01). In our hands, laparoscopic cholecystectomy carries a lower risk of serious complications than the open procedure.

Bile leak after cholecystectomy significance and treatment: results from the National Norwegian Cholecystectomy Registry.

From April 1993 to July 1995, altogether 3860 procedures were enrolled in the Norwegian National Cholecystectomy Registry (NNCR), 777 (20.2%) being open operations. 3083 (79.8%) were initiated laparoscopically, 313 (10.2%) of these converted to open technique. Mortality within 30 days after open cholecystectomy was 1.9%, after a converted procedure 1.0% and 0.14% after laparoscopic cholecystectomy (p<0.01). According to the intention to treat principle, converted procedures should be included in the laparoscopic group. This gives seven deaths after 3083 procedures, i.e. 0.23%. Postoperative death still occurs approximately 10 times more frequently after open cholecystectomy (p<0.01). However, this is partly due to selection of high risk cases to open technique. Postoperative bile leak was observed in 25 patients (0.9%) in the laparoscopic, 13 (4.2%) in the converted and 19 (2.4%) in the open group. Bile leak contributed significantly to serious complications. 37 major problems were observed in 25 of the patients (44%). Five patients died (8.8%). Among the 57 bile leak patients, common bile duct (CBD) injury was found in 13 (22.8%). Additional 19 CBD injuries occurred, presenting with other symptoms such as icterus, or being recognised during the first operation. The frequency of CBD injury in the laparoscopic group was 14 (0.5%), in the converted group 12 (3.8%) and in the open group 6 (0.8%). None of the patients with CBD injury underwent intraoperative cholangiography. The present results firstly show that open cholecystectomy cannot be considered a safe procedure for high risk patients, secondly, that postoperative bile leak contributes significantly to postoperative mortality and hence is a serious condition generating from CBD injury in about 1/5 of all cases.

[A national registry for cholecystectomy. Quality assurance with practical consequences?]. / Landsregister for kolecystektomi. Kvalitetssikringstiltak med praktiske konsekvenser.

Altogether 2,120 patients have been enrolled in the Norwegian Cholecystectomy Registry during the first 18 months after it was established. 1,699 patients (80%) were operated on laparoscopically. In 174 (10.2%) the operation was changed to an open procedure. 421 (20%) were operated on primarily using an open technique. The main quality problems were mortality (1.2%) and injuries of the common bile duct (0.95%) associated with open cholecystectomy. These frequencies are far above the values stated in available literature, and two interpretations are possible: Only the best results tend to be published internationally, and our results may be representative for the national average frequencies of serious complications in other countries too. On the other hand, the present results may disclose inadequate quality insufficiency and a need for improvement. The possible actions seem to be: Firstly, to try harder to avoid open cholecystectomy in seriously ill patients (ASA 3-4). If possible, they should not be operated on at all. When surgery is essential, a laparoscopic technique seems to cause less cardiopulmonary complications. Secondly, an improved dissection technique in open (and laparoscopic) surgery is necessary in order to reduce the frequency of injuries of the common bile duct.

[Laparoscopic cholecystectomy as ambulatory surgery. Safety requirements, benefit potential and patient satisfaction]. / Laparoskopisk kolecystektomi som dagkirurgi. Sikkerhetskrav, gevinstpotensial og pasienttilfredshet.

Ambulatory laparoscopic cholecystectomy was attempted using a new anaesthetic regimen in 50 patients. 46 patients were discharged 3-5 hours after operation, four were admitted to and remained in hospital for 1-5 days, one for psychosocial reasons, one because of emesis and two because of extended surgery. 45 of 46 ambulatory patients were generally satisfied after having experienced ambulatory cholecystectomy. Postoperative pain and nausea were moderate. Only 24% needed parenteral opioids postoperatively, and only 30% needed anti-emetic treatment. One woman suffered unacceptable pain and discomfort during the first two days at home, and would not prefer to have ambulatory treatment (questionnaire). Four patients were readmitted. Two had a forgotten stone in the common bile duct and underwent ERCP to extract the stone, without further complications. The third had a clip occluding the common bile duct. She was reoperated on in order to remove the clip and insert a T-tube in the common bile duct. Finally one woman was readmitted because of abdominal pain and vomiting, of which we never found the cause. She recovered spontaneously. Even though serious complications associated with biliary surgery were unavoidable in this ambulatory series, we have documented that patients can be operated on safely in this way. Most patients were very content, and experienced much less postoperative discomfort than they had expected.