MATERIALS AND METHODS

SUBJECTS (Studies I-III)

When evaluating the personal learning curve and outcome of laparoscopic hysterectomy, the first 100 consecutive patients operated on from October 1992 through December 1993 in Helsinki University Central Hospital were studied. Patient selection was carried out prospectively and for inclusion it was required that the approximate weight of the uterus should be less than 500 g, the patient should not be excessively obese and no severe adhesions should be expected. The hospital records were retrospectively studied on previous operations, operative bleeding, operating time (time from the first incision to the last suture), hospital stay (calculated by subtracting the admission date from the discharge date) and recovery time (written sick leave) after a follow-up visit at two to four weeks (Study I).

A national register was founded to analyze the nationwide outcome of laparoscopic hysterectomies. Questionnaires were sent to every hospital and information concerning previous operations, indications, surgical techniques and difficulties, operating time, hospital stay, recovery time (written sick leave), and complications was asked. The data were registered immediately after the operation and after the scheduled follow-up visit after one month. A total of 1165 patients were followed prospectively from January 1,1993 to December 31,1994. Information regarding the follow-up visit was available for 875 (75%) patients. The total number of laparoscopic hysterectomies checked from the hospital records was 1216 over the study period, so the response rate was 96% (Study II).

In study III, fifty women aged between 30 and 70 years scheduled for abdominal hysterectomy because of a benign condition were randomized to undergo abdominal or laparoscopic hysterectomy. Short-term clinical outcome, complications and tissue trauma were evaluated among patients operated on from March through September, 1997 in Jorvi Hospital. Exclusion criteria were major medical diseases, body mass index above 32 kg/m2, size of uterus larger than that at 14 weeks of pregnancy or uterine width greater than 10 cm in transvaginal ultrasonography, severe adhesions or endometriosis, prolapse and any other contraindication for laparoscopy. Written informed consent was obtained and the study was approved by the local ethics committee. Women were advised to call to the hospital whenever any problems occurred and they were followed-up until the sick leave ended and they were completely recovered.

REGISTERS (Studies IV-VI)

The Finnish Hospital Discharge Register and Care Register

From 1990 through 1993 the numbers of different laparoscopic procedures were acquired from the Finnish Hospital Discharge Register, which contains information regarding diagnosis, dates of admission and discharge, and surgical procedures on each inpatient. The accuracy of the main diagnosis has been 95% and that of the surgical procedures 90-95% (Keskimäki et al. 1994). The Register was used for research, administration, and planning, and it was maintained by the National Board of Health (Keskimäki and Aro 1991). From 1994 the data were collected more accurately on all inpatients and most outpatients to the Finnish Hospital Care Register, which is maintained by the National Research and Development Centre for Welfare and Health. Every hospital collects data using a standardized data sheet and sends it automatically to the Register at the end of each year. The diagnoses were coded according to the Finnish version of the International Classification of Diseases, 9th Revision (ICD-9) and according to the 10th Revision (ICD-10) from 1996. The surgical procedures were coded according to the classification by the Finnish Hospital League (Toimenpidenimikkeistö, 1983) and from 1997 according to the Nordic Classification of Surgical Procedures (Classification of Surgical Procedures, 1996).

Laparoscopic procedures were divided into three categories as they were coded in the register: diagnostic laparoscopies, laparoscopic sterilization, and operative laparoscopies. Diagnostic laparoscopies involved only procedures carried out in connection with infertility or dysmenorrhea without any extra procedure. Both the Filshie and the Hulka clips were used for laparoscopic sterilization and in a minority of cases tubal electrocoagulation was used. Operative laparoscopy was defined as procedures carried out in connection with endometriosis, ectopic pregnancy, adhesions, and ovarian cysts as well as myomectomy and laparoscopic hysterectomy. Up to 1996, the codes for laparoscopies included procedures carried out by both gynecologists and surgeons. To identify only gynecological laparoscopies we cross-examined the procedures with diagnoses and included only procedures with gynecological diagnoses.

The numbers of total and subtotal abdominal and vaginal hysterectomies carried out in association with benign conditions were easy to obtain from the register because they all had a surgical code of their own. However, the number of laparoscopic hysterectomies was more difficult to find because the surgical procedure classification had no specific code for laparoscopic hysterectomy until 1997. The first laparoscopic hysterectomy was performed in 1992 in Finland and in the first year only eleven procedures were carried out (Mäkinen et al. 1994). The numbers of laparoscopic hysterectomies in 1993 and 1994 were taken from the national register of laparoscopic hysterectomies (see study II) and the number for 1995 was collected from all Finnish hospitals by means of questionnaires. In 1996, a national, prospective survey of all hysterectomies performed in Finland in one year was undertaken (the Finhyst study, Johansson et al., unpublished data) and it revealed the number of laparoscopic hysterectomies in that year. Since 1997 laparoscopic hysterectomy has had a unique code and it is easy to assess the numbers.

The National Patient Insurance Association

The Patient Injury Act was brought into force on the first of May 1987 in Finland. The Ministry of Social Affairs and Health agrees on the premium basis and the insurance terms. All insurance companies engaged in patient insurance are members of the Association and all compensation is paid from insurance premiums. In order to obtain full compensation for patient injury, proof of malpractice is no longer required. The Patient Injury Act ensures compensation for patient injury that 1) probably has arisen as a consequence of examination or treatment; 2) has been caused by an infection or inflammation that probably originated in circumstances connected with examination or treatment; 3) has been caused by an accident connected with examination or treatment or occurred during patient transport or resulted from a defect in medical care equipment or in a medical care device. However, inevitable complications, necessary risk-taking or drug-related injuries are not usually "patient injuries" with the exception of unreasonable consequences after any procedures. Patient Insurance covers all those engaged in the practice of health care or medical care, in both the public and private sectors, improving the legal protection of patients and medical staff. Most importantly, Patient Insurance effectively decreases the number of malpractice trials in courts. Every Finnish hospital has an official patient ombudsman, who helps the patient in preparing a claim when necessary. Patients are informed when coming to the hospital of the Patient Injury Act and the Association and it is the patient who reports the injury to the Association.

We tested the accuracy of the Association by comparing complications reported to the national register of laparoscopic hysterectomies in 1993-1994 (study II) with complications reported to The National Patient Insurance Association. All major complications were in both registers but some bladder perforations sutured laparoscopically during the primary operation were not reported to The National Patient Insurance Assosiation. In addition, we compared complications of laparoscopic hysterectomy in 1996 reported to The National Patient Insurance Association with those reported in one year's prospective survey on hysterectomies during the same year in Finland (Finhyst study, unpublished data). We found out that a higher number of ureteral injuries, the same number of intestinal injuries but a lower number of bladder injuries were reported to the Association than to the Finhyst study.

Complications were divided into minor and major complications. Minor complications were usually not compensated but almost all major complications were compensated by the Association. Minor complications included infections and hemorrhages requiring no hospitalization, and failed sterilizations. Major complications consisted of injuries to the gastrointestinal tract, urinary tract and large vessels, as well as nerve paresis, deep venous thrombosis, and unintended procedures such as those carried out in connection with postoperative hemorrhage and incisional hernias. The complication rates were analyzed separately in different laparoscopic procedures and according to different organs. In addition, urinary tract injuries after different techniques of hysterectomy were analyzed separately.

METHODS

Operative techniques (Studies I-III)

In study I, the ligaments were divided with staplers or electrocoagulation and uterine vessels were secured by using clips, staplers or electrocoagulation. The uterus was removed and the vaginal cuff was sutured vaginally. In study II, the operative technique varied among different hospitals but bipolar and monopolar electrocoagulation were used in all operations, staples in 28%, clips in 16%, and sutures in 4% of the procedures. Uterine vessels were cut laparoscopically in 86%, uterosacral ligaments in 80%, part of the cardinal ligaments in 65%, and the anterior or posterior vaginal fornix in 62% of the operations. In a randomized study (III), bipolar coagulation and scissors were used to cut ligaments and uterine vessels and the uterus was removed vaginally when performing laparoscopic hysterectomy. Patients randomized to undergo abdominal hysterectomy were operated on in a standard manner through a lower midline or Pfannestiel incision as described by Thompson and Warshaw (1996). Diathermy was only used for hemostasis and no peritoneal closure was performed.

Analysis of biochemical markers (Study III)

Fasting venous blood samples were drawn preoperatively on the day of surgery and afterwards on the first, second and seventh postoperative day as well as during the first follow-up visit at four weeks. Urine samples were also examined every time to rule out urinary tract infection. Blood hemoglobin, hematocrit and serum CRP concentration were determined by standard laboratory procedures on the day of sampling. Serum CRP levels were measured by immunoturbidometric assay (Hitachi 911, Japan). The sera for IL-6, TATI and CA 125 measurements were stored at -20 oC in individual tubes and all samples were analyzed in the same assay. Concentrations of IL-6 were determined by enzyme immunoassay (huIL-6 ELISA kit, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Netherlands), those of TATI by radioimmunoassay (1277 GammaMaster®, EG & T Wallac, Finland) and those of CA 125 by immunoradiometric assay (IRMA-mat®, Byk-Sangtec Diagnostica GmbH & Co, Germany). The detection limit for IL-6 was 7.4 pg/mL and in calculations this was divided in half and a value of 3.7 pg/mL was used when the levels were below the detection limit. The detection limit for TATI was 5 ug/L and that for CA 125 was 10 kU/L. Values of 2.5 ug/L and 5 kU/L were used, respectively, when the levels were below the detection limit.

STATISTICS

Studies I and II were descriptive but we compared operating times against different variables by simple regression analysis in study I. Study III was randomized and for statistical analysis of variables between the two hysterectomy groups, and changes in the concentrations of biochemical markers between the groups, two-sample Student's t-tests assuming unequal variances were used. The 2 test was used for comparison of proportions among hysterectomy groups. A sample size was calculated to achieve statistical differences between two surgical groups (Peipert et al. 1995). Twenty-one women in each group would be needed for 90% study power and for differentiation of 10 mg/L (one standard deviation) between the means of CRP concentration when type I error is 5%. For 80% study power, 15 women in each group would be needed. Twenty-five women were enrolled in each group but tissue trauma was analyzed as regards 18 uncomplicated hysterectomies in each group. In study IV complications of hysterectomy were analyzed and for statistical analysis of variables between different hysterectomy groups, two-sample Student's t-test assuming unequal variances was used. Fisher's exact two-tailed test and the 2 test were used when comparison of proportions among hysterectomy groups was carried out. In studies V and VI complications of laparoscopy were analyzed and differences between complication rates were analyzed by the 2 test. Relative risk (RR) and 95% confidence intervals (95% CIs) were applied to complications following various operative laparoscopies, and 95% CIs were also applied when reporting percentages. In all studies statistical significance was defined as P 0.05.