Title:
The epidemiology and risk factors for recurrence after inguinal hernia surgery.

Abstract:
Recurrence after inguinal hernia surgery is a considerable clinical problem, and several risk factors of recurrence such as surgical technique, re-recurrence, and family history have been identified. Non-technical patient related factors that influence the risk of recurrence after inguinal hernia surgery are sparsely studied. The purpose of the studies included in this PhD thesis, was to describe the epidemiologic characteristics of inguinal hernia occurrence and recurrence, as well as investigating the patient related risk factors leading to recurrence after inguinal hernia surgery. Four studies were included in this thesis.
Study 1: The study was a nationwide register-based study combining the Civil Registration System and the Danish National Hospital Register during a five-year period. We included a total of 46,717 persons operated for a groin hernia from the population of 5,639,885 people (2,799,105 males, 2,008,780 females). We found that 97% of all groin hernia repairs were inguinal hernias and 3% femoral hernias. Data showed that inguinal hernia surgery peaked during childhood and old age, whereas femoral hernia surgery increased throughout life. Study 2: Using data from the Danish Hernia Database (DHDB), we included all male patients operated for elective primary inguinal hernia during a 15-year period (n = 85,314). The overall inguinal hernia reoperation rate was 3.8%, and subdivided into indirect inguinal hernias and direct inguinal hernias, the reoperation rates were 2.7% and 5.2%, respectively (p <0.001, chi-square). In the multivariate Cox proportional hazards analysis of factors predicting reoperation, we found that a direct inguinal hernia at primary operation was a substantial risk factor for recurrence with a Hazard ratio of 1,90 (CI 95% 1.77-2.04) compared with an indirect inguinal hernia at primary operation (p < 0.001). We found that there was a significant relationship between the type of hernia at the primary operation and reoperation, when controlling for the effect of the operation method, r = 0.45 (p < 0.001). This corresponded to odds ratios (OR) of 7.1 (CI 95% 6.0-8.4) of being reoperated for a direct inguinal hernia if the hernia at the primary operation was a direct inguinal hernia, and an OR of 3.0 (CI 95% 2.7-3.3) of being reoperated for an indirect inguinal hernia if the primary operation was for an indirect inguinal hernia. As subsequent findings, we saw that the frequency of laparoscopic hernia repair increased during the study period and that the laparoscopic repair of indirect inguinal hernias recurred more often than indirect inguinal hernias operated by Lichtenstein's technique (p < 0.001). Study 3: Using data from the DHDB, we included all female patients operated for elective primary inguinal hernia during a 15-year period (n = 5,893). Of those, a total of 305 operations for recurrences were registered (61 % inguinal recurrences, 38 % femoral recurrences, 1 % no hernial), which corresponded to an overall crude reoperation rate of 5.2%. A noticeable difference was found in reoperation rates after primary operation for direct inguinal hernias (DIH), indirect inguinal hernias (IIH) and combined IIH+DIH of 11.0%, 3.0%, and 0.007% respectively (p < 0.001, chi-square). In the multivariate Cox proportional hazards analysis of factors predicting reoperation, we found that a direct inguinal hernia at primary operation was a substantial risk factor for recurrence with a Hazard ratio of 3.1 (CI 95% 2.4-3.9) compared with an indirect inguinal hernia at primary operation (p < 0.001). Laparoscopic operation was found to give a lower risk of recurrence with a Hazard ratio of 0.57 (CI 95% 0.43-0.75) compared with Lichtenstein's technique (p < 0.001). We found that all femoral recurrences (n = 116) occurred after Lichtenstein's procedure and none occurred after laparoscopic operation (p < 0.001, Log Rank test). Study 4: This study was a systematic review and meta-analysis of non-technical patient-related risk factors for recurrence after inguinal hernia surgery. From a total of 5,061 potentially relevant records we included 40 studies in the review covering 719,901 procedures in 714,167 patients and of those 14 studies covering 378,824 procedures in 375,620 patients were included into meta-analysis of eight risk factors (gender, age, hernia type, hernia size, re-recurrence, bilaterality, mode of admission and smoking). We found that female gender (RR 1.38, 95% CI 1.28-1.48, I2 = 0%), direct inguinal hernias at primary procedure (RR 1.91, 95% CI 1.62-2.26, I2 = 10%), operation for a recurrent inguinal hernia (RR 2.2, 95% CI 2.0-2.42, I2 = 6%), and smoking (OR 2.53, 95% CI 1.43-4.47, I2 = 0%) were risk factors for recurrence after inguinal hernia surgery. Furthermore, emergency admission; connective tissue composition and degradation; and positive family history were found to have an impact on the risk of recurrence, while post-operative convalescence and age had no impact on the risk of recurrence.
The studies included in the thesis have studies the natural history of groin hernias on a nationwide basis; have identified the epidemiologic distribution of groin hernias and the non-technical risk factors associated with recurrence. Data showed that non-technical patient-related risk factors have great impact on the risk of recurrence after inguinal hernia surgery. The reason to why inguinal hernias recur is most likely multifactorial and lies in the span of technical and non-technical patient-related risk factors and it is possible that the different groin hernia subtypes have different pathophysiology. This knowledge should be implemented into clinical practice in order to reduce the risk of recurrence and in future research design examining recurrence after inguinal hernia surgery as outcome.