Long-term efficacy and safety of aromatase inhibitor use for leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata is a rare disease characterized by pelvic smooth-muscle nodules of various sizes. It is sometimes misdiagnosed as ovarian or peritoneal carcinoma metastasis; therefore, surgical excision for pathological diagnosis is required. Treatment options include bilateral salpingo-oophorectomy (BSO), gonadotrophin-releasing hormone agonist therapy, and aromatase inhibitor therapy. All of these suppress estrogen levels, but a standard treatment has not been established. A 40-year-old woman had multiple pelvic tumors, suspicious for ovarian cancer. She underwent laparotomy, where frozen sections of the nodules revealed leiomyomatosis peritonealis disseminata. After she completed gonadotrophin-releasing hormone agonist therapy, we performed a total abdominal hysterectomy and BSO with residual-nodule resection, but the nodules recurred 6 months after surgery. We then started letrozole, and 3 years have now elapsed without nodule enlargement or development of new lesions. The long-term use of aromatase inhibitor therapy is thought to be effective and safe for patients with recurrence after BSO.

Novel MRI finding for diagnosis of invasive placenta praevia: evaluation of findings for 65 patients using clinical and histopathological correlations.

OBJECTIVE: To review established magnetic resonance (MR) criteria and describe a new MR finding for the diagnosis of invasive placenta praevia. METHODS: A retrospective review of prenatal MRI examinations of 65 patients (median age: 35 years) who underwent MR for the screening of invasive placenta praevia. All MRIs were performed on a 1.5-T unit, including axial, coronal and sagittal T2-weighted half-Fourier single-shot turbo spin echo imaging. Fifteen patients were diagnosed with invasive placenta praevia. Two experienced radiologists reviewed the MR images and evaluated a total of six MRI features of the placenta, including our novel finding of the placental protrusion into the internal os (placental protrusion sign). Inter-rater reliability was assessed by using kappa statistics. Features with a kappa statistic >0.40 were evaluated using Fisher's two-sided exact test for comparison of their capabilities for placental invasion assessment. RESULTS: Interobserver reliability was moderate or better for the intraplacental T2 dark band, intraplacental abnormal vascularity, uterine bulging, heterogeneous placenta and placental protrusion sign. Fisher's two-sided exact test results showed all these features were significantly associated with invasive placenta praevia. CONCLUSION: The novel MRI finding of a placental protrusion sign is a useful addition to the established MRI findings for the diagnosis of invasive placenta praevia. KEY POINTS: • Prenatal diagnosis for an invasive placenta is essential for perinatal planning. • Magnetic resonance imaging provides useful information for the diagnosis of invasive placenta. • The placental protrusion sign is a useful novel MRI finding for predicting invasive placenta.

Estimation of the vitamin D (VD) status of pregnant Japanese women based on food intake and VD synthesis by solar UV-B radiation using a questionnaire and UV-B observations.

Although vitamin D (VD; serum 25 hydroxyvitamin D) deficiency (< 20 ng/mL) is widespread among Japanese women, the VD status among pregnant women is unknown. This study aimed to determine the VD status of pregnant Japanese women during different meteorological seasons and to determine the factors controlling VD status. A total of 309 pregnant Japanese women were recruited at 28 weeks of gestation at the gynecology department of a university hospital in Tokyo between August 2018 and October 2019. Blood samples were collected to measure serum 25(OH)D levels. Two questionnaires were completed: a brief self-administered dietary history questionnaire (BDHQ) and an outdoor exposure history questionnaire to determine skin sunlight exposure and the use of sunscreen. Among the recruited subjects, 268 were included in the statistical analysis. The average VD intake from food was 9.0 µg/day, the average VD synthesis from UV-B was 15.2 µg/day, and the average sum of VD intake and nominal VD synthesis was 24.1 µg/day; this exceeded the recommended 2011 Dietary Reference Intake for the USA and Canada (15.0 µg/day). However, the average serum 25(OH)D level (11.4 ng/mL) was very low, indicating widespread VD deficiency. Serum 25(OH)D and VD synthesis by solar UV-B were significantly correlated only during the high UV-B season. The 25(OH)D level was weakly correlated with the VD intake from food in all seasons. We obtained a statistically significant correlation between serum 25(OH)D level and VD intake from food using the BDHQ. We also obtained a statistically significant correlation between the serum 25(OH)D level and VD synthesis from solar UV-B exposure, especially during the high UV-B season. Our logistic regression analysis model predicted VD deficiency in 88.0% of subjects. Our method might be possible to be used to predict the VD status of pregnant Japanese women, although another validation cohort is needed to verify the ability of the estimation equation.

Association between uterine repair at laparoscopic myomectomy and postoperative adhesions.

OBJECTIVE: To determine whether uterine repair at laparoscopic myomectomy influences postoperative adhesions. DESIGN: Retrospective study. SETTING: University-affiliated hospital. POPULATION: A total of 108 patients who underwent second-look laparoscopy after laparoscopic myomectomy without concomitant pelvic surgery between January 2006 and May 2010. METHODS: Absorbable cellulose adhesion barriers were used for uterine repair at initial surgery in all women. The presence of adhesions was evaluated by second-look laparoscopy. MAIN OUTCOME MEASURES: The influence of background factors (diameter of largest myoma, number of myomas, incision sites and number of suture layers) and the uterine status immediately after uterine repair at laparoscopic myomectomy (number, length and location of wounds, as well as wound appearance classified as virtually normal, swollen or protruding) on adhesion formation were analysed in 108 women with 296 uterine wounds. Data were analysed by logistic regression analysis. RESULTS: Forty-one (38.0%) women had adhesions to their uterus at follow up. We identified 48 (16.2%) adhesions among 296 wounds in all women. A protruding wound was significantly associated with postoperative wound adhesion (odds ratio, 2.53; p=0.02). The number of enucleated subserosal myomas (odds ratio, 3.29; p<0.001) and the diameter of the largest myoma (odds ratio, 1.05; p<0.001) were significantly associated with wound protrusion, which was a critical factor influencing adhesion. CONCLUSIONS: Postoperative wound adhesion formation seems to depend on uterine status immediately after laparoscopic myomectomy.

Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve.

AIM: The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38 years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls. MATERIAL AND METHODS: Sixty-one patients were found to have ovarian endometriomas and 42 patients non-endometriotic cysts. A small amount of normal ovarian tissue was obtained during ovarian cystectomy. The follicles in normal ovarian tissue and resected cyst walls were histologically evaluated. RESULTS: The density of follicles in ovarian tissues correlated with the age of the patients in both groups. In women aged <35 years, the relative density of follicles in healthy ovarian tissues was consistently lower in the endometriotic cyst group compared to the non-endometriotic cyst group, with the relative ratio at age 20, 30 and 35 years calculated to be 35.4%, 46.8% and 62.7%, respectively. There was no significant difference between the groups in patients over the age of 35. The resection rate of normal ovarian tissue in cystectomy specimen of the endometriosis group was significantly higher than in the non-endometriotic cyst group (P < 0.001). CONCLUSIONS: Our data suggest that ovarian endometriomas have a detrimental impact on follicle reserve in younger patients. Further, laparoscopic cystectomy for endometriomas may accelerate the rate of oocyte loss associated with aging.

Retrospective analysis of the efficacy of perioperative use of the cell salvage and autologous blood recovery system during laparoscopic myomectomy.

PURPOSE: To evaluate the benefit of the intraoperative use of a cell salvage and autologous blood recovery system during laparoscopic myomectomy (LM). METHODS: We retrospectively reviewed the medical records of 538 patients who underwent LM between January 2008 and December 2009 at our hospital. Patients undergoing LM were divided into two groups depending on whether the cell salvage and autologous blood recovery system was used; the use of the system was at the discretion of the surgeon. The system for intraoperative hemorrhage was employed based on the surgeon's decision. RESULTS: Of the 583 patients, 23 patients (4.3%) underwent LM using the system. No patient required an allogeneic blood transfusion during or after the surgery. The median surgical time (183 vs. 100 m), total blood loss (520 vs. 100 mL), total weight of enucleated myomas (390 vs. 175 g), and postoperative calculated δ-Hemoglobin (δ-Hb) (2 vs. 1.6 g/dL) were significantly increased in the 23 patients in whom the system was used. The median autologous blood volume recovered by intraoperative use of the system and transferred to the 23 patients was 250 mL (range 125-800 mL). For patients in whom the system was not used, the total blood loss significantly correlated to δ-Hb (r = 0.29; P < 0.01). However, there was no such correlation in patients in whom the system was not used (r = 0.04; P = 0.86). CONCLUSIONS: The adoption of a cell salvage and autologous blood recovery system during LM was useful for patients with severe hemorrhage.

Learning curve of minimally invasive two-port laparoscopic myomectomy.

UNLABELLED: BACKGROUND AND OBJECTS: To examine the learning curve of minimally invasive 2-port total laparoscopic myomectomy (TTLM). METHODS: TTLM was performed by using only umbilicus and left inguinal ports, for 30 patients at our university affiliated hospital between May 2009 and February 2010. The times required for each of the 5 surgical phases of the early and late cases performed by the same surgeon were compared by using a DVD time counter. RESULTS: The mean surgical time was 82.5±5.2 minutes, blood loss was 42.1±7.5mL, and weight of specimen was 65.3±13.3g. The eighth case was the first in which the surgical time fell below the overall mean surgical time. Comparison of the mean time of each phase between the 7 early and the subsequent (late) cases revealed significant differences in the times required for suturing. CONCLUSIONS: Although this was a feasibility study, the results suggest that this technique can be mastered after 7 cases. Learning curve, Suturing.

Use of magnetic resonance analysis for clinical evaluation of the peripheral area of gestational sac in bleeding and non-bleeding ectopic pregnancy cases.

PURPOSE: To evaluate preoperative magnetic resonance (MR) imaging features of bleeding and non-bleeding ectopic pregnancy (EP) by comparison with surgical findings. METHODS: Eighteen suspected EP cases underwent preoperative MR imaging. We classified 8 cases as the bleeding group and 7 cases as the non-bleeding group with or without intra-abdominal bleeding and/or hematoma at the site of EP, and compared, retrospectively, gestational sac (GS)-like structure, particularly the peripheral area of the GS via MR analysis. Excluded were 3 cases that were insufficient for assessing extrauterine GS-like structure: ruptured tubal pregnancy and uterine horn pregnancy. RESULTS: GS-like structures were typically observed as low intensity on T1-weighted image (T1WI) and as high intensity on T2-weighted image (T2WI). In non-bleeding cases, most peripheral areas of the GS were of intermediate intensity on T1WI and high intensity on T2WI. Most bleeding cases were of high intensity on T1WI and low to high intensity on T2WI. Furthermore, the peripheral area of the GS was of higher intensity on T1WI with fat suppression than on T1WI. CONCLUSIONS: It is clear that MR imaging is effective for diagnosis of cases of suspected EP. EP conditions may be predicted by signal intensity of the peripheral area of the GS via MR analysis.

Successful pregnancy with stage IB2 uterine cervical cancer: A case report.

BACKGROUND: Although cervical cancer is one of the most common malignancies in pregnancy, its management mainly follows the guidelines for nonpregnant disease state. Within the limited time, patients, and healthcare workers must make difficult decisions to either delay treatment until documented fetal maturity or start immediate treatment based on the disease stage. CASE: The patient was a 37-year-old woman: gravida 1, para 0. Her cervical cytology revealed a high-grade squamous intraepithelial lesion at 8 weeks' gestation. Moreover, invasive squamous cell carcinoma was suspected based on the findings of uterine cervix biopsy. Cervical conization was performed at 11 weeks' gestation, confirming a histopathological diagnosis of squamous cell carcinoma, pT1b2. Cervical cytology findings continued to be negative for intraepithelial lesion or malignancy from 2 weeks after conization until 2 weeks before a cesarean section. In addition, we performed abdominal pelvic lymphadenectomy at 16 weeks' gestation to determine whether the patient could continue her pregnancy. No lymph node metastasis or local recurrence was observed. Finally, a cesarean section and modified radical hysterectomy were performed at 35 weeks' gestation. There was no carcinoma invasion or metastasis. A baby girl weighing 2056 g was delivered with 1- and 5-min Apgar scores of 8 and 9, respectively. Five years postoperatively, there was no evidence of cancer recurrence. CONCLUSION: Management of cervical cancer during pregnancy by using a combination strategy of deep conization and pelvic lymphadenectomy could be an effective strategy for carefully and safely assessing risks of recurrence and metastasis.

Utility of an organ retraction sponge (endoractor) in gynecologic laparoscopic surgery.

Because it is minimally invasive, laparoscopic surgery is preferred over open surgery. However, it is often difficult to maintain an adequate surgical field during the procedure. As in open laparotomy, securing an adequate surgical field is important for adequate visualization. We evaluated the effectiveness and safety of the Endoractor, an organ retraction sponge that can be inserted through a 12-mm trocar to secure a surgical field in gynecologic laparoscopic surgery. The Endoractor, a 100% cellulose compressed sponge, can be expanded using physiologic saline solution, with the result that the swollen sponge displaces organs away from the surgical field. Between October 2009 and April 2010, we used the Endoractor in 24 patients, placed in a Trendelenberg position, during laparoscopic surgery. In no patients, even with return to a horizontal position, did the intestines fall into the pelvis, and surgery was easily performed. Mean (SD; 95% CI) operative time was 92.7 (44.5; 74.0-111.6) minutes, and blood loss was 54.1 (73.1; 22.9-82.1) mL. All patients were discharged on postoperative day 3. Even with the patient in a horizontal position without use of the Trendelenberg position, the Endoractor enables a good surgical field to be secured. It remains to be seen whether this device works as well in obese patients.

Alterations in endometrial vascular density via hysteroscopy evaluated by vascular analysis software during laparoscopic myomectomy on an infertile woman with submucous myoma.

Submucous myomas cause infertility and recurrent pregnancy loss. Several studies have reported successful reproductive outcomes after hysteroscopic myomectomy (HM), but the risk of postoperative intrauterine adhesion is present. We performed laparoscopic myomectomy (LM) for a submucous myoma and second look laparoscopy under observation using a hysteroscope to evaluate the alteration in endometrial vascular density during surgery using vascular analysis software. The patient was a 33-year-old nulliparous infertile woman. She had one submucous myoma of 4 cm in diameter and 50-60% penetration into the myometrium (class T:II; the European Society of Hysteroscopy classification). The surface vascular density of the submucous myoma was 68.6% before the start of surgery, decreased to 51.4% upon vasopressin injection and increased to 67.6% at the end of LM. Intraabdominal and intrauterine adhesions were not seen at second look laparoscopy. The vascular density was 70.8%, and the rate of endometrial blood flow was increased to 112.5% by comparison with the vascular density before the start of surgery. HM is a safe and effective procedure, but carries the risk of scarring the uterine cavity with uterine adhesions. We have to consider LM for women of reproductive age who have a submucous myoma with penetration >50% into the myometrium (class T:II).

A new instrument: a flexible hysteroscope with narrow band imaging system: optical quality comparison between a flexible and a rigid hysteroscope.

There are two different types of hysterocopes available: Flexible and rigid. Flexible scopes have the ability to observe the whole intrauterine cavity, but it is difficult to perform an operation on endometrial lesions. Rigid hysteroscopes provide superior optical qualities due to higher pixel count. We report the use of a new flexible hysteroscope with narrow band imaging (NBI) system (HYF-V EndoEYE Flexible Video Hysteroscope) and compared the optical qualities of this flexible to those of a rigid hysteroscope using the vascular analysis software "SolemioENDO ProStudy". Twenty-four images of endometrium in eight cases, and 12 images of submucous myoma in six cases were each photographed by two the hysteroscopes. The vascular densities of both endometrium and myoma under conventional light in the flexible scope were significantly higher than with the rigid scope. However the vascular densities under narrow-band light in the two scopes were not significantly different. The vascular densities of the images taken by flexible scope were higher than the images taken by rigid scopes under conventional light. With the rigid scope, microvascular structure may be crumpled by high water pressure. A flexible hysteroscope with NBI system has superior ability to observe the intrauterine cavity and measure vascular density compared to a rigid scope.

Linear salpingotomy with suturing by single incision laparoscopic surgery for tubal ectopic pregnancy.

We investigated the feasibility of linear salpingotomy with suturing for ampullary tubal pregnancy via single incision laparoscopic surgery (SILS). Three patients underwent SILS between April and May 2010 at our hospital due to ampullary tubal pregnancy. A multichannel port was inserted into the umbilicus via a 2.5-cm incision to accommodate a 5-mm flexible laparoscope and a disposable articulating forceps. The linearly incised Fallopian tube was intracorporeally sutured using an articulating suturing device dedicated to SILS. The mean surgical duration was 54 minutes. Tubal preservation by linear salpingotomy was accomplished for all patients without up-conversion to conventional laparoscopy. Serum ß-hCG values of all patients immediately decreased and further medical treatment was unnecessary.

Evaluation of factors contributing to uterine scar formation after laparoscopic myomectomy.

OBJECTIVE: To evaluate factors contributing to uterine scar formation after laparoscopic myomectomy (LM) and to estimate whether uterine scarring indicated risk of uterine rupture. DESIGN: Retrospective study. SETTING: University-affiliated hospital. POPULATION: A total of 692 patients who underwent second-look laparoscopy (SLL) after LM. METHOD: Video-tape recording during SLL to evaluate the conditions of uterine suture wound healing, with univariate and logistic regression analysis. MAIN OUTCOME MEASURES: Correlation between scar formation and operative findings at LM. Factors influencing scar formation in 305 patients with an enucleated solitary myoma. RESULTS: SLL revealed that 628 patients (90.8%) had a normal uterus and 64 patients (9.2%) had a scarred uterus. Deformation of the endometrium found by preoperative imaging and complete myometrial penetration during LM had a positive correlation and the number of enucleated myomas a negative correlation with scar formation. Significant factors associated with scar formation were complete myometrial penetration (odds ratio, 2.53; 95% confidence interval, 1.30-4.93; p = 0.006) and enucleation of a subserosal myoma (odds ratio, 0.23; 95% confidence interval, 0.08-0.70; p = 0.009). Of the 98 patients who delivered, none suffered a uterine rupture regardless of the presence of a uterine scar. CONCLUSIONS: Uterine scar formation after LM correlated with the degree of myometrial penetration. However, the presence of a uterine scar did not appear to influence the delivery outcome.

The impact of endometriosis, endometrioma and ovarian cystectomy on assisted reproductive technology.

PURPOSE: To assess outcomes in assisted reproductive technology (ART) in infertile women with endometriosis with respect to their concomitant endometrioma status and surgical history in our department. METHODS: This is a retrospective case control study which analyzes informational data obtained at a university hospital. The study drew from a patient pool of 332 cases (877 cIVF/ICSI cycles) that took place in our department from 2006 to 2008. Sixty-one cases (97 cycles) had major indications for cIVF/ICSI with endometriosis. We classified groups from these 61 cases as follows: an unoperated endometrioma group (A) with 31 cycles, a postoperative endometrioma group (B) with 51 cycles, and a no endometrioma group (C) with 15 cycles. We analyzed and compared these three groups and also included a non-endometriosis tubal infertility group (D) with 27 cycles. RESULTS: In the control group (D), serum FSH levels and the cancellation rates were significantly lower than those of other groups, and the number of developing follicles was higher. E2 levels before oocyte aspiration in the postoperative endometrioma group (B) was lower. Implantation, pregnancy, delivery and miscarriage rates were not significantly different among the four groups. CONCLUSION: The results suggest that endometriosis causes a decrease in endocrinologic ovarian function whether or not an endometrioma is also present. As for E2 level before oocyte aspiration, our results suggest that ovarian reserves might be reduced by endometrioma excision, but this is difficult to evaluate. In the endometriosis groups, cancellation rates were significantly higher, although when embryos were transferred the pregnancy rates were not significantly different when compared with the non-endometriosis group. As for infertile women with endometriomas, our results suggest that preexisting ovarian reserve is reduced by the presence of endometriosis, and ovarian reserve might also be reduced by excision of endometriomas.

Erratum to: The impact of endometriosis, endometrioma and ovarian cystectomy on assisted reproductive technology.

[This corrects the article DOI: 10.1007/s12522-009-0021-1.].

Polycystic ovary syndrome with asynchronous bilateral adnexal torsion in a natural cycle.

Cases involving polycystic ovaries (PCOs) with adnexal torsion in a natural cycle without ovulation induction are rare, and no reports of such cases have described asynchronous bilateral adnexal torsion. Here, we report a case of PCO syndrome (PCOS) with asynchronous bilateral adnexal torsion in a natural cycle. The patient was a 37-year-old woman with a history of 2 gravidas 1 para. Her primary complaint was left lower abdominal pain. Ultrasonography and MRI identified multiple uterine myomas occupying the pelvis and the left ovary, with oedematous swelling that had moved ventrally to the uterus. She was diagnosed with adnexal torsion and underwent emergency laparoscopic adnexectomy. Nine months after surgery, she experienced right lower abdominal pain. Ultrasonography revealed suspected right adnexal torsion and she underwent emergency surgery. The right ovary was twisted 540° counterclockwise and swollen to 7 cm in size, with partial polycystic changes. She was histopathologically diagnosed with a PCO, and the final diagnosis, which also considered the endocrine test results, was PCOS. In PCOS, adnexal torsion may occur if the swollen ovary moves because of a hysteromyoma or other cause. Accordingly, torsion should be considered during the follow-up of patients with PCOS.

Systemic Treatment Patterns With Advanced or Recurrent Non-small Cell Lung Cancer in Japan: A Retrospective Hospital Administrative Database Study.

PURPOSE: Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. METHODS: This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed. Regimens were examined by histology, age, sex, and therapeutic line. Logistic regression analysis was performed to predict which clinical and demographic factors affected patients' probability of receiving first- or second-line therapy or completing first-line platinum-based chemotherapy. FINDINGS: Among 16,413 patients, 67.9%, 39.2%, and 22.3% received first-, second-, and third-line systemic treatment, respectively. Treatment was more common in patients aged <75 versus ≥75 years (76.0% vs 51.6%), in female versus male patients (71.6% vs 65.4%), and in patients with nonsquamous versus squamous disease (75.6% vs 61.9%). More than 30 systemic regimens were administered. The most common first-line therapy was platinum-based chemotherapy (nonsquamous, 53.6%; squamous, 73.7%). Non-platinum-based chemotherapy use increased in the second-line setting, but platinum-based chemotherapy use remained high (nonsquamous, 33.9%; squamous, 38.6%). Tyrosine kinase inhibitors were used in 32.0% and 29.4% of patients with nonsquamous NSCLC in the first- and second-line settings, respectively. Switches from first- to second-line platinum-based chemotherapy and from first- to second-line tyrosine kinase inhibitors occurred. Forty-two percent of the patients died during hospitalization. In the logistic regression analysis, factors associated with a decreased likelihood of receiving first-line therapy were male sex, squamous histology, age >75 years, treatment at a general (vs cancer-specific) hospital, worse scores on certain activities of daily living, presence of chronic pulmonary disease, worse Hugh-Jones classification, and positive smoking status. The likelihood of completing first-line platinum-based chemotherapy was increased with greater body mass index, better activities of daily living scores, absence of chronic pulmonary disease, and better Hugh-Jones classification. The likelihood of continuing with second-line therapy was decreased with older age and recurrence of NSCLC. IMPLICATIONS: Systemic treatment patterns for advanced or recurrent NSCLC in Japan were varied. Nearly 30% of all patients and approximately half of elderly patients did not receive systemic treatment. Treatment rates declined with subsequent therapeutic lines. Generally, guidelines were followed with first-line treatment administration, but not with second-line administration. These results underscore the need for better guideline adherence and more optimal treatment in and elderly patients and in those receiving later-line treatment in Japan.

Cost-minimisation analysis of sivelestat for acute lung injury associated with systemic inflammatory response syndrome.

OBJECTIVES: To conduct a cost-minimisation analysis of sivelestat sodium hydrate treatment for patients in the intensive care unit (ICU) with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS) caused by infection. DESIGN: The analysis was performed based on data from a phase III randomised, multicentre, double-blind, controlled clinical study of up to 14 days treatment with sivelestat, in which the effect of intravenous sivelestat at a high dose (0.20 mg/kg/h; the sivelestat group) was compared with that at a low dose (0.004 mg/kg/h, effectively a placebo; the control group). PATIENTS: Patients with ALI associated with SIRS caused by infection, who began their treatment under mechanical ventilation management in the ICU. METHODS: A four-stage Markov model was constructed to represent the possible conditions of an ALI patient: ICU plus intubated mechanical ventilation; ICU plus weaned from a mechanical ventilator; admission to the general ward; and death. The base-case analysis used a mechanical ventilator weaning daily rate of 2.9% for the control group and 4.0% for the sivelestat group, and the same mortality (1.2%) for both groups at all stages of the Markov model. Medical costs were estimated from standard fees and Japanese National Health Insurance drug prices included fees for hospitalisation within the ICU and general wards, mechanical ventilation, examinations and drug expenditure. Costs were in 2001 values. Sensitivity analyses were performed by varying the weaning rate, mortality, time between weaning and discharge to the general ward, and drug costs. PERSPECTIVE: Payers of healthcare costs. MAIN OUTCOMES: The expected 30-day medical costs per patient in the control and sivelestat groups were Japanese yen (yen) 4,144,887 and 3,975,451 yen, respectively; a difference of 169,436 yen. Drug expenditure accounted for more than half of the medical costs for each group. The periods under mechanical ventilation management and in the ICU for the sivelestat group were shorter than those for the control group by 2 and 1.8 days, respectively. This was of significance in the reduction of the medical costs. A sensitivity analysis suggested that the expected costs for the sivelestat group exceeded those for the control group when the daily weaning rate for the sivelestat group was <3.5%, and also when mortality rates were set at 0.9% in the sivelestat group and 1.4% in the control group. CONCLUSIONS: This analysis suggests that from the Japanese healthcare payer perspective, treatment with sivelestat may reduce medical costs compared with standard care for patients with ALI associated with SIRS caused by infection.

The role of neutrophil elastase in acute lung injury.

Beside its physiological function as a powerful host defense, neutrophil elastase is also known as one of the most destructive enzymes in the body. Current notion holds that neutrophil elastase is able to escape from regulation by multiple protease inhibitors at inflammatory sites. Once unregulated, this enzyme disturbs the function of the lung permeability barrier and induces the release of pro-inflammatory cytokines. These actions then cause symptoms that are typical in the pathophysiology of acute lung injury. In this article, we review recent progress in the understanding of the physiological activity of neutrophil elastase and its role in acute lung injury. Evidence in this review that supports the involvement of neutrophil elastase in the pathophysiology of acute lung injury includes: (1) neutrophil elastase levels are increased in both clinical and animal models of acute lung injury; (2) topical or systemic administration of neutrophil elastase produces typical symptoms of acute lung injury both in vitro and in vivo; and (3) inhibition of increased neutrophil elastase activity reduces symptoms of acute lung injury in animal models. A greater understanding of the role of this enzyme in the pathophysiology of acute lung injury will lead to better treatments for this complicated disease.