Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of inguinal hernia.

BACKGROUND: According to a Cochrane review, laparoscopic inguinal hernia repair compares favourably with open mesh repair, but few data exist from surgical practice outside departments with a special interest in hernia surgery. This study compared nationwide reoperation rates after laparoscopic and Lichtenstein repair, adjusting for factors predisposing to recurrence. METHODS: Some 3606 consecutive laparoscopic repairs were compared with 39 537 Lichtenstein repairs that were prospectively recorded in a nationwide registry between 1998 and 2003. Patients were subgrouped according to type of hernia: primary or recurrent and unilateral or bilateral. Overall reoperation rates and 95 per cent confidence intervals were calculated. Long-term reoperation rates were estimated using the Kaplan-Meier method. RESULTS: The overall reoperation rates after laparoscopic and Lichtenstein repair of unilateral primary indirect hernia (0 versus 1.0 per cent), primary direct hernia (1.1 versus 3.1 per cent), unilateral recurrent hernia (4.6 versus 4.8 per cent) and bilateral recurrent hernia (2.6 versus 7.6 per cent) did not differ. However, laparoscopic repair of a bilateral primary hernia was associated with a higher reoperation rate than Lichtenstein repair (4.8 versus 3.0 per cent) (P = 0.017). CONCLUSION: Laparoscopic repair compared favourably with Lichtenstein repair for primary indirect and direct hernias, and unilateral and bilateral recurrent hernias, but was inferior for primary bilateral hernias.

Quality assessment of 26,304 herniorrhaphies in Denmark: a prospective nationwide study.

BACKGROUND: Groin hernia repair is one of the most frequent operations, but there is no consensus about surgical or anaesthetic technique. Furthermore, no nationwide studies have been done. Our aim was to investigate outcome results of groin hernia surgery to improve quality of treatment. METHODS: We prospectively recorded 26304 groin hernia repairs done in Denmark from Jan 1, 1998, to June 30, 2000, in a nationwide Danish hernia database. FINDINGS: 93% of all groin herniorrhaphies done in Denmark in the 30 months of the study were recorded in the database. Kaplan-Meier estimates of reoperation rates 30 months after anterior mesh repair and laparoscopic repair were significantly lower than after sutured posterior wall repairs in primary inguinal hernia (2.2% and 2.6% vs 4.4%; p<0.0001). Reoperation rates were also lower with anterior mesh repair (6.1%; p<0.0001) and laparoscopic repair (3.4%; p<0.0001) than with sutured posterior wall repair (10.6%) after recurrent hernia. Use of Lichtenstein mesh repair increased from 33% in January, 1998, to 62% in June, 2000, whereas use of laparoscopic repair remained constant at about 5%. Kaplan-Meier estimates of reoperation rates were 2.8% in the first 15 months and 1.6% in the second (p=0.03). For elective repairs, only 59% of patients were treated on an outpatient basis, and only 18% had local anaesthesia. INTERPRETATION: Mesh repairs have a lower reoperation rate than conventional open repairs. Systematic prospective recording of treatment and outcome variables in a national clinical database improved the overall quality of surgical care. However, there is a large potential for cost savings and more efficient patient care with extended use of mesh techniques, outpatient surgery, and local anaesthesia.

Randomized clinical trial of laparoscopic versus open inguinal hernia repair.

BACKGROUND: Several studies have suggested that better results are obtained after laparoscopic repair of inguinal hernia than after conventional operation. This is most obvious for bilateral and recurrent hernias but less accepted for primary unilateral hernias. METHODS: This was a randomized clinical trial comparing transabdominal preperitoneal laparoscopic repair with the Shouldice technique in patients with primary unilateral hernia. Some 138 patients were randomized to laparoscopic hernia repair and 130 to open surgical repair. RESULTS: The complication rates in the two groups were similar. In the laparoscopic group the patients returned to work more rapidly with a median time of 13 versus 18 days (P < 0.005) and had a shorter period of analgesia intake with a median time of 2.1 versus 2.7 days (P < 0.02). The follow-up was 97.8 per cent complete. At a median of 12 months, four recurrences (2.9 per cent) were detected in the laparoscopic group and three (2.3 per cent) in the open group. CONCLUSION: This study shows that in patients with a primary unilateral hernia laparoscopic repair results in less postoperative pain and a quicker recovery than open repair.

[Laparoscopic herniotomy in recurrent inguinal hernia]. / Laparoskopisk herniotomi ved recidiv af lyskebrok.

We present a material of 103 patients with a total of 105 recurrent inguinal hernias operated by transabdominal laparoscopic repair. Nine patients developed seromas. One was reoperated due to ileus and one had the mesh removed because of persistent pain in the groin. Following a median observation of 12 months (range 4-48 months) 102 patients were examined and two new recurrences were detected corresponding to 1.9% (95% confidence limits 0.2-6.7%).

Late mesh rejection as a complication to transabdominal preperitoneal laparoscopic hernia repair.

BACKGROUND: The use of a mesh in transabdominal preperitoneal laparoscopic hernia repair (TAPP) caries the risk of late rejection or infectious complications related to the mesh. The aim of this study was to describe the extent of these complications. METHODS: We performed a retrospective study of 500 consecutive patients with TAPP for inguinal hernia. RESULTS: Late mesh rejection was observed in three patients at 5-19 months after surgery. The mesh was removed via a suprapubic midline incision. At 3-4 month's follow-up, none of the patients had recurrence of the hernia, even though no hernia repair had been done. CONCLUSION: Late mesh rejection is a potential complication of TAPP and has to be considered when choosing the surgical method of hernia repair.

Athymic experimental animals in pharmaco-immunological research.

Immunodeficient animals--the nude mouse and the nude rat--allow studies of drug action and possible side effects without interference from the immune system. Comparative investigations in athymic and euthymic animals allowed us to elucidate the role of T-lymphocytes in the pathogenesis of streptozotocin-induced diabetes mellitus in mice, and the importance of NK-cells as effectors in guanethidine-induced sympathectomy in the rat. It is suggested that immunodeficient animals should be included in toxicological studies of xenobiotics.

Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats.

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.

Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats.

Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but not prevent the initiation of an immunological reaction in the ganglia. Natural killer cells could only be identified in ganglia following guanethidine treatment alone. It is concluded that anti-asialo GM1 treatment can prevent the guanethidine-induced sympathectomy by eliminating the natural killer cells from the ganglia.

Fatal adverse drug reactions reported in Denmark 1968-1988.

During the period 1968-88 a total of 27,938 reports on adverse drug reactions (ADR) were received through the voluntary reporting system in Denmark, of which 713 concerned fatal reactions. Excluding cases of overdosage, congenital malformations and unclassifiable reactions, 590 reports were selected for analysis. Of 215 drugs involved, 41% were marketed before 1968. When corrected for drug consumption figures no significant differences in incidence were found with age and gender. The most frequently reported drug groups were antirheumatics (92), cytostatics (54), antibiotics (53) and oral contraceptives (50). Over-the-counter drugs were involved in 13 reports. Fatal drug interactions were reported in 17 cases. In general the duration of treatment was longer in cases of fatal ADR than the average for ADR as a whole. The diagnoses most frequently reported were bone marrow depression (105), "sudden unexpected death" (57), anaphylactic shock (30) and malignant disease (23). The incidence of fatal thromboembolism involving oral contraceptives was halved following the withdrawal of high-estrogen preparations resulting in an incidence over the period 1983-88 of 1 per 141, 000 user years. The corresponding figure concerning non-steroidal antiinflammatory agents was 1 fatal ADR per 26,000 treatment years. Halothane-induced hepatic damage was reported in 33 cases during 1968-83, but only in 2 cases over the period 1983-88. The number of fatal ADR following use of inhaled adrenergic antiasthmatics was 19 during 1968-83, but 0 during 1983-88 despite a sale corresponding to 360,000 treatment years. Lactate acidosis following oral antidiabetics was reported in 18 cases during 1968-78, but only in 1 during 1978-88 following the withdrawal of phenformin. The annual number of reported fatal ADR remained fairly constant throughout the period despite the introduction of numerous potent drugs. Subject to reservations reflecting the shortcomings inherent in a retrospective analysis of data from a voluntary ADR reporting system, the risk of a fatal ADR is considered extremely low, being estimated at 6 per million inhabitants per year and 1 per 180,000 treatment years.

Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy.

Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an infiltration of small inflammatory cells. By means of monoclonal antibodies these cells were identified. The number of B-lymphocytes increased following guanethidine in both athymic and euthymic rats. The number of T-lymphocytes increased to a great extent in euthymic rats, but was virtually missing in athymic rats. The number of NK-cells and monocytes/macrophages increased in both athymic and euthymic rats. The conclusion is, that guanethidine exerts a direct effect on sympathetic ganglion cells followed by a thymus-independent immune response.

Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects.

The pharmacokinetics of orally administered idarubicin (22.5 mg/m2/week) and idarubicinol were studied for 12 weeks in 14 patients with breast cancer. Plasma concentrations were monitored for 72 hours after the first, fourth, and twelfth doses and trough concentrations after 1, 2, 3, 4, 5, 7, 11, and 12 weeks of treatment. The half-lives of idarubicin and idarubicinol were 19 and 60 hours, respectively. No time-dependent changes or cumulation were observed. The metabolic ratio showed little variation. The plasma AUCs of idarubicin and idarubicinol varied between patients but were fairly constant in individual patients. The sum of the plasma AUCs was lower in patients with rapid progression than in patients who responded to treatment. A correlation between this parameter and the relative decrease in the leukocyte counts was demonstrated (p less than 0.05). No correlation was found between the pharmacokinetic parameters and the time to final progression.

Guanethidine-induced sympathectomy in the nude rat.

Guanethidine sulphate 40 mg/kg was administered intraperitoneally daily for 14 days to normal Lewis rats and athymic nude rats of a Lewis background (rnu/rnu). Histological examination of the superior cervical ganglia demonstrated a pronounced chromatolysis of the neurones and a loss of the major part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus-independent immune-response or by a direct toxic effect.

Single or multiple doses of metronidazole and ampicillin in elective colorectal surgery. A randomized trial.

A randomized trial including 294 patients was performed to evaluate the prophylactic effect of single vs. multiple doses of antibiotics in elective colorectal surgery. All patients received 1.5 g metronidazole and 3.0 g ampicillin peroperatively and were randomized to: no further prophylactic antibiotic treatment, or ampicillin 1 g X 3 and metronidazole 0.5 g X 3 given intravenously during the second and third postoperative days. Deep wound infection was seen in 9/149 (6 percent) receiving a single dose and in 8/145 (6 percent) receiving multiple doses. No differences were found in the two groups between frequencies of anastomotic dehiscences, intra-abdominal abscesses, sepsis, and pulmonary infections. The two groups were similar according to distribution of sex, age, diagnosis, and type of surgery. A single peroperative dose of metronidazole and ampicillin is a simple and satisfactory antibiotic prophylaxis in elective colorectal surgery.

Topical ampicillin in addition to a systemic antibiotic prophylaxis in elective colorectal surgery. A prospective randomized study.

Prophylactic use of topical ampicillin in addition to intravenous ampicillin and metronidazole was studied in a randomized trial including 203 consecutive patients undergoing elective colorectal surgery. All received ampicillin, 1 g X 3, and metronidazole, 0.5 g X 3, intravenously for at least three days from induction of anesthesia, and 105 also received topical ampicillin, 1 g, in each of the surgical wounds. Deep wound infection or dehiscence was seen in 12 of 105 having both administrations of antibiotics, and in nine of 98 having only intravenous antibiotics. The two groups were similar according to distribution of sex, age, type of surgery, and efficiency of bowel preparation. Topical ampicillin should be omitted in elective colorectal surgery when systemic prophylaxis with ampicillin and metronidazole is used.

Testicular torsion in newborn.

Five cases of testicular torsion in newborn are presented. Four infants had an extravaginal and one an intravaginal torsion. All were operated on, three had an orchiectomy and two an orchiopexy. It is emphasized that surgery should be performed only under optimal conditions to arrive at the exact diagnosis and to reveal the type of torsion. In case of intravaginal torsion contralateral fixation should be done.