Japanese Journal of Clinical Oncology 32:103-107 (2002)
© 2002 Foundation for Promotion of Cancer Research
Comparison of the Results of Radical Hysterectomy: Sequential Observations in Each Period
Gynecology, Reproductive and Developmental Medicine, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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Background: The efficacy of drains and of antibiotics for prophylaxis of postoperative retroperitoneal infections following radical hysterectomy with systematic lymphadenectomy has not yet been adequately investigated.
Methods: Patients who had just undergone radical hysterectomy were divided into three groups. We used a retroperitoneal drain transvaginally for Groups A (n = 54) and B (n = 55) and transabdominally for Group C (n = 103). Group A was administered a first- and Groups B and C a second- or third-generation cephem antibiotic as the prophylactic antibiotic. We compared the surgery time, blood loss, fever index and febrile morbidity in these three groups.
Results: The average surgery time was Group A 344.2 ± 13.7 min (mean ± SE), Group B 425.6 ± 11.0 min and Group C 528.2 ± 10.9 min. A significant difference was observed among the groups (p < 0.05). In terms of blood loss during surgery, a significant increase (p < 0.05) occurred in Groups B (2400 ± 196 g) and C (2373 ± 130 g) compared with Group A (1820 ± 122 g). For fever index, Group A showed a value of 36.1 ± 2.7 dh, Group B 19.9 ± 2.4 dh and Group C 8.8 ± 1.5 dh. A significant difference was observed among the groups (p < 0.01). In terms of febrile morbidity, significant differences (p < 0.01, p < 0.0001) were observed between Groups B (14.6%) and C (8.7%) in comparison with Group A (44.4%), respectively.
Conclusion: In radical hysterectomy with systematic lymphadenectomy, it may be preferable to choose transabdominal drains in the retroperitoneal space and second-generation cephem antibiotics for prophylaxis of postoperative retroperitoneal infections.
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INTRODUCTION |
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Radical hysterectomy [Class III; Piver–Rutledge classification (1)] with systematic lymphadenectomy is performed primarily as a treatment for cervical carcinoma of the uterus. Since this surgery includes extensive lymphadenectomy, it can result in stagnation of postoperative blood and lymphatic fluid and exudation in the retroperitoneal space, thus easily inducing postoperative retroperitoneal infection. For the prophylaxis of postoperative retroperitoneal infection, drains are placed in the retroperitoneal space to discharge quickly blood, lymphatic fluid and any exudations.
There are primarily two methods of placing the retroperitoneal drain. These involve transvaginal or transabdominal suction drainage. We used transvaginal suction drainage between 1978 and 1987 for the retroperitoneal drain (2); either transvaginal suction drainage or transabdominal drainage, depending on the case, between 1988 and 1992; and transabdominal drainage only between 1992 and 2000.
With the rapid development of antibiotics in recent years, those providing prophylaxis against postoperative infections are constantly changing. Since the discovery of cephaloridine and cephalothin in 1962, cephem antibiotics have replaced penicillin antibiotics as the first choice for prophylaxis of postoperative infections (3,4). We used the first-generation cephem antibiotic as the first choice for radical hysterectomy with systematic lymphadenectomy between 1978 and 1979. However, since 1985, we have been using second- or third-generation cephem antibiotics (2).
In this study, we evaluated retrospectively the efficacy of drains in the retroperitoneal space and that of antibiotics in prophylaxis of postoperative retroperitoneal infections.
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PATIENTS AND METHODS |
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Participants
From all patients undergoing radical hysterectomy with systematic lymphadenectomy at the Hokkaido University Hospital as a surgical treatment for cervical carcinoma of the uterus, we extracted 212 patients for the present study: Group A patients who underwent radical hysterectomy between 1978 and 1979 (n = 54; age range 32–64 years; median age 46 years), Group B patients between 1985 and 1987 (n = 55; 31–68 years; 50 years) and Group C patients between 1992 and 2000 (n = 103; 26–72 years; 48 years).
For patients in Groups A and B the retroperitoneal drain was used transvaginally and for those in Group C the drain was placed transabdominally. With regard to the first-choice prophylactic antibiotic, Group A was administered 1.0 g/day (range 1.0–2.0 g/day) of a first-generation (cefalotin sodium, cefazolin sodium and cefapirin sodium) cephem antibiotic for 5 days (5–7 days) and Groups B and C were administered 1.0 g/day (1.0–2.0 g/day) of a second- (cefotiam dihydrochloride, cefamandole sodium, cefmetazole sodium, cefoxitin sodium, cefminox sodium and cefbuperazone sodium) or third-generation (cefotaxime sodium, cefmenoxime hemihydrochloride, ceftriaxone sodium and ceftazidime) cephem antibiotic for 5 days (5–8 days).
There was no significant difference in patient age among Groups A, B and C. In terms of the clinical stage of cervical carcinoma [the FIGO staging system (5)], Group A was comprised of 23 patients at stage I (42.6%), 24 at stage II (44.4%) and seven at stage III (13.0%), Group B 18 patients at stage I (32.7%), 28 at stage II (50.9%) and nine at stage III (16.4%) and Group C 51 at stage I (49.5%), 44 at stage II (42.7%) and eight at stage III (7.8%). We observed no statistically significant difference in stages among the groups.
Surgical Procedure
There has been little change in the surgical procedures for radical hysterectomy itself. However, we have expanded the region of lymph node dissection in systematic lymphadenectomy over time. More specifically, in 1978 and 1979, we dissected the lymph nodes in the pelvis and the para-aortic lymph nodes in the lowest region. However, between 1985 and 1987, the top end of the region of dissection was expanded to include the para-aortic lymph nodes below the inferior mesenteric artery. Furthermore, since 1992, the top end of the lymphadenectomy has been widened to include the para-aortic lymph nodes below the renal veins.
After radical hysterectomy, postoperative management of the vagina is performed to prevent vaginal shortening (6). Hemostasis of the vaginal stump is achieved, followed by suturing of only the peritoneum, leaving the vaginal vault open to the retroperitoneal space. Thereafter, to prevent its early closure, the vaginal vault is kept open by mechanical means.
Surgery Time and Blood Loss During Surgery
To evaluate indirectly the degree of invasion, which is considered to affect the onset of postoperative infections, we compared Groups A, B and C with regard to surgery time and blood loss during surgery.
Bacteriological Examination
We used a Y-shaped closed-drain tube (2) for retroperitoneal transvaginal drainage and a suction closed-drain for bilateral transabdominal drainage, both of which were placed during surgery. When the amount of daily drainage fell below 50 ml (4.1 ± 0.2 postoperative days, mean ± SE), we removed the drains, exchanging them for French catheters. By culturing bacteria in the removed drain tips, we examined the frequency of positive bacterial cases. We also classified the detected bacteria by Gram’s stain and compared the incidence of Gram-positive coccus and Gram-negative bacillus. Moreover, we examined the breakdown of the Gram-positive coccus.
We used the Bacteriological Analytical Manual (BAM) methods (7) for culturing aerobes and the anaerobic chamber method (8) for culturing anaerobes. For bacterial classification, we followed Bergey’s Manual of Systematic Bacteriology (9).
Fever Index and Febrile Morbidity
To evaluate the clinical effects of drainage and antibiotics, we measured the patients’ body temperature four times daily (at 6 a.m., 10 a.m., 2 p.m. and 6 p.m.) for 7 days, excepting the 24 h postoperative absorption fever period. We then calculated the fever index (10) (degree hour; dh), which was the integral value of 37°C or higher on the fever chart. Moreover, we compared the generation-by-generation fever index of cephem antibiotics in the groups for which transvaginal retroperitoneal drainage had been conducted (Groups A and B).
We also studied the febrile morbidity (11), i.e. the frequency of having a temperature of 38°C or higher, of Groups A, B and C.
Statistical Analysis
Statistical analyses were conducted using StatView J-5.0 PPC (SAS Institute, Cary, NC). To identify statistically significant differences among groups, we used the 
2 test, Student’s t-test and one-factor analysis of variance (ANOVA).
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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Surgery Time and Blood Loss During Surgery
Group A recorded an average surgery time of 344.2 ± 13.7 min (mean ± SE), Group B 425.6 ± 11.0 min and Group C 528.2 ± 10.9 min. A significant difference in surgery time was observed among the groups (p < 0.05) (Fig. 1). Blood loss was determined as 1820 ± 122 g (mean ± SE) in Group A), 2400 ± 196 g in Group B and 2373 ± 130 g in Group C. Compared with Group A, a significant increase (p < 0.05) occurred in Groups B and C.
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Bacteriological Examination
Thirty-five of 54 patients (64.8%) in Group A, 49 of 55 (76.4%) in Group B and only 14 of 103 (13.6%) in Group C were identified as positive for bacteria as determined by bacterial culture. Compared with Group C, Groups A and B had a significantly higher (p < 0.0001) positive bacterial rate (Table 1). Based on classification by Gram’s stain of the bacteria detected in bacterial culture, Groups B (81.6%) and C (85.7%), compared with Group A (28.6%), showed a significant increase (p < 0.001, p < 0.0005, respectively) in Gram-positive coccus. In contrast, Groups B (18.4%) and C (14.2%), compared with Group A (71.4%), showed a significant decrease (p < 0.0001) in Gram-negative bacillus (Table 2). When examining the breakdown of Gram-positive cocci, a notable proportion of Staphylococcus epidermidis or Enterococcus faecalis was detected in all groups, although in Group C a decrease in Enterococcus faecalis was observed (Fig. 2).
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Fever Index and Febrile Morbidity
In a comparison of the fever index among groups, a significant difference was observed (p < 0.01). Group A showed a value of 36.1 ± 2.7 dh (mean ± SE), Group B 19.9 ± 2.4 dh and Group C 8.8 ± 1.5 dh (Fig. 3).
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With regard to the fever index among patients in whom transvaginal retroperitoneal drainage was utilized and only the cephem antibiotic was administered postoperatively, the patient group administered the first-generation cephem antibiotic showed a value of 35.3 ± 2.7 dh, the second-generation group 17.0 ± 2.3 dh and the third-generation group 15.8 ± 5.3 dh. Compared with the first-generation cephem group, the second- and third-generation cephem groups showed a significant decrease (p < 0.01) in the fever index.
With regard to febrile morbidity, Group A accounted for 44.4% (24 out of 54 patients), Group B 14.6% (8/55) and Group C 8.7% (9/103) of those with febrile morbidity. A significant difference (p < 0.01, p < 0.0001) was observed between Groups B and C, respectively, and Group A.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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Since this investigation regarding surgery time and blood loss was a retrospective study covering 23 years, it is impossible to make comparisons without considering influential factors such as advances in surgical equipment and anesthesia and other surgical techniques. However, it should be noted that the decline in immune function of the host could have easily caused postoperative infections in our patients, at least in those in Groups B and C, if not in those in Group A. As the method of classifying group subjects, we used a chronological classification of surgery, not a classification based on the antibiotics used, in order to understand the effect of invasion in surgery.
In a comparison between Groups A and B, we examined the differences caused by using different antibiotics for prophylaxis of postoperative retroperitoneal infections when the same method of placing the retroperitoneal drains was used (2). The results showed no statistically significant difference in the positive bacterial rate among groups. However, in the examination of the fever index and febrile morbidity, we observed a significant decrease in these two parameters in Group B in comparison with Group A. These results suggest that for first-choice antibiotics for prophylaxis of postoperative retroperitoneal infections, second- or third-generation cephem is recommended rather than first-generation cephem.
In the comparison between Groups B and C, assuming that the first-choice postoperative antibiotic was similar, we examined differences that may have been caused by the different methods of placing the retroperitoneal drains. The results suggested that the drains placed transabdominally had a higher Gram-positive rate based on bacterial culture. Overall, the transabdominally placed drains showed lower values for the fever index and the febrile morbidity of postoperative infections. Since both Groups B and C were given the second- and third-generation cephem as first-choice antibiotic, 80% or more of the detected bacteria were Gram-positive coccus and 20% or less were Gram-negative bacillus. This result does not contradict the results expected from the antibiotics used (12,13). Examination of the breakdown of the increasing amount of Gram-positive coccus showed it to be primarily Staphylococcus epidermidis and Enterococcus faecalis, which are known to be normal bacterial flora of the skin and vagina (14). S. epidermidis was often observed on the abdominal wall and E. faecalis in the vagina.
Necrotic tissues without blood flow or the presence of foreign objects prevent the arrival of phagocytes, making bacterial growth easy. The local hypoxic state due to ischemia can provide a good environment for the growth of anaerobes (15). We discharged blood and lymphatic fluid from the retroperitoneal space and, to prevent local infections, placed drains there until the amount of postoperative draining had decreased. However, long-term drain placement can be interpreted as a failure of the physical functions of local protection (16). The skin and mucous membranes or the mucus produced from mucous membranes prevent bacteria from causing tissue infection. However, surgical procedures sometimes cause a prophylactic mechanism in the host’s skin, causing mucous membranes to fail, allowing enteric or vaginal bacteria in normal bacterial flora, which have a symbiotic relationship with the host, into the tissue.
In the procedure to prevent vaginal shortening (6), the vaginal vault is kept open to prevent early closure. Therefore, when a transperitoneal drain is placed transvaginally, it is possible that indigenous bacteria in the vagina can invade the retroperitoneal space. This phenomenon may explain why the positive bacteria rates of Groups A and B were high compared with that of Group C. At present, it is not well understood what first-choice antibiotic should be used and how long it should be administered. The prophylactic use of antibiotics should be minimal if retroperitoneal drains are placed transabdominally and those drains should be removed as soon as possible, but this management may not be available with the procedure to prevent vaginal shortening.
The major difference between the second- and third-generation cephem antibiotics is the latter’s enhancement of the antibiotic effect against Gram-negative bacillus and the expanded area of antibiotic protection against anaerobes (12,13). However, it is well known that owing to the frequent use of third-generation cephem antibiotics, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) has increased. In general, an anaerobic bacterial infection occurs as follows: aerobes are infected, the oxidation–reduction potential at the infected local site drops and the amount of the existing anaerobe increases, thus generating an anaerobic infection (15). This sequence implies that it may be possible to prevent anaerobic infections if aerobic infections after surgery are successfully and quickly eliminated. The increase in MRSA and no significant difference in the fever index between the groups receiving the second- and the third-generation cephem antibiotics in the present study suggest that it is preferable to choose a second-generation cephem antibiotic with an antibiotic spectrum against bacteria in normal bacterial flora of the vagina, such as Staphylococcus aureus, Escherichia coli and Enterobacter, in semi-aseptic surgery such as radical hysterectomy with systematic lymphadenectomy.
The prophylaxis of infections after malignant tumor surgery leads not only to early discharge from the hospital but also to speedy postoperative treatments, specifically chemotherapy or radiotherapy, thereby improving patient prognosis. Lastly, considering the increasing number of antibiotic-resistant bacteria such as MRSA, a discussion of the first-choice postoperative antibiotic is extremely important to clinicians who, like the authors, deal with gynecological malignant tumors on a daily basis.
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Acknowledgment |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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The authors thank the late Dr Chinami Saito, who would have been a contributing author of this paper, for providing samples and investigating clinical records and for helpful comments pertinent to the present study.
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FOOTNOTES |
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+ For reprints and all correspondence: Ritsu Yamamoto, Gynecology, Reproductive and Developmental Medicine, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-8638, Japan. E-mail: rityam@med.hokudai.ac.jp
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Received November 2, 2001; accepted December 28, 2001.
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