Comparison of the primary cesarean hysterotomy scars after single- and double-layer interrupted closure.

INTRODUCTION: It is unclear whether hysterotomy closure techniques can affect niche development. Therefore, this study aimed to analyze the effect of single-layer and double-layer interrupted closures of hysterotomy incisions during primary cesarean section on the formation of uterine niches. MATERIAL AND METHODS: A prospective cohort study of women undergoing primary cesarean section was performed between June 2011 and July 2014. Saline contrast sonohysterography was used to measure the niche depth and residual myometrium. The ratio of the niche depth to the sum of the niche depth and residual myometrium thickness (niche ratio) was calculated. RESULTS: Niches were identified in 14/58 (24.1%) women with single-layer sutures and 55/209 (26.3%) women with double-layer sutures (p = 0.74). Single-layer closure was associated with more than a five-fold increase in the odds of a niche ratio ≥0.4 (odds ratio 5.59; 95% CI 1.71-18.28). CONCLUSION: Single-layer closure may be associated with an increased risk of larger niches (niche ratio ≥0.4), although it may not increase the overall frequency of niche formation.

Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study.

BACKGROUND: Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. METHODS: We conducted a phase II study in which patients were administered paclitaxel 175 mg/m(2) over a 3-h period followed by carboplatin (area under the serum concentration-time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. RESULTS: Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48-77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2-7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. CONCLUSION: This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

Phase II clinical study of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 101 Group Study).

OBJECTIVE: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents. PATIENTS AND METHODS: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0). RESULTS: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%). CONCLUSIONS: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Histopathological prognostic factors predicting para-aortic lymph node metastasis in patients with endometrioid uterine cancer.

INTRODUCTION: The purpose of this study was to determine histopathological factors for para-aortic lymph node (PALN) metastasis in patients with endometrioid uterine cancer. METHODS: A total of 355 patients (Stage I, n=269; II, n=24; and III, n=62) (FIGO 2009) underwent primary radical surgery including complete systematic pelvic lymph node (PLN) and PALN dissection in Tohoku Gynecologic Cancer Unit (TGCU) between 1993 and 2004. Logistic regression analysis was used to determine the independent prognostic factors for PALN metastasis. RESULTS: Multivariate analysis revealed that PLN metastasis (p<0.0001) and ovarian metastasis (p=0.0080) related with PALN metastasis. Moreover, among the sites of PLN metastases, obturator lymph node (LN) [risk ratio (RR): 16.9, 95% confidence interval (CI): 4.3-66.4, p<0.0001] and common iliac LN (RR: 7.1, 95% CI: 1.1-44.5, p=0.0375) related with PALN metastases. In detection of PALN metastasis, combination of obturator LN and/or common iliac LN and/or ovarian metastasis (A) revealed 75.9% sensitivity (22/29) and 97.8% negative predictive value (NPV) (304/311). However, by combination of obturator LN metastasis and/or common iliac LN metastasis and/or grade 3 and/or deep myometrial invasion (B), the detection of PALN metastasis was 100.0% sensitivity (29/29) and 100.0% NPV (198/198). Also, 55.8% (198/355) of patients could have avoided PALN dissection by combination B. CONCLUSIONS: These results suggest that PALN dissection is necessary when combination B is positive by pre- and intra-operative assessments. Further prospective randomized controlled studies need to be conducted in a larger patient population to establish the strategy for detecting PALN metastasis utilizing pre-/intra-operative assessments.

Mayer-Rokitansky-Kustner Hauser syndrome complicated by either uterine leiomyoma or ovarian tumor.

A 50-year-old Japanese woman with Mayer-Rokitansky-Kustner-Hauser syndrome and two pelvic tumors underwent laparotomy. Laparotomy revealed that no torsion of the right ovarian tumor had occurred, with uterine leiomyoma originating from the right side of a rudimentary uterus. Histopathological examination demonstrated leiomyoma of the rudimentary uterus with positive staining for estrogen and progesterone receptors, and mucinous cyst adenoma of the right ovary. Uterine leiomyoma is rare in this syndrome and the present report represents the first published case complicated by ovarian tumor.

Scleroderma-like cutaneous lesions induced by paclitaxel and carboplatin for ovarian carcinoma, not a single course of carboplatin, but re-induced and worsened by previously administrated paclitaxel.

Scleroderma-like cutaneous lesion as an adverse event from paclitaxel and carboplatin has been reported. No report shows the occurrence of scleroderma-like cutaneous lesions from a single course of carboplatin. The patient is a 67-year-old female, administered paclitaxel and carboplatin as neoadjuvant chemotherapy. Following four courses, scleroderma-like cutaneous lesions were demonstrated. Skin biopsy corresponded to histopathological findings of scleroderma. Immunological investigation shows only antinuclear antibodies are positive. The characteristic Raynaud's phenomenon of scleroderma and hemorrhagic spots on the cuticles were not found. Postoperatively, a single course of carboplatin treatment was given. Scleroderma-like cutaneous lesions re-induced and worsened. This is the first report detailing scleroderma-like cutaneous lesions induced by previously administrated paclitaxel that worsened by carboplatin.

Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence.

OBJECTIVES: To determine the relationship between histopathological prognostic factors and sites of initial recurrence in endometrioid uterine cancer. METHODS: A total of 355 patients (Stage I, n=227; II, n=38; III, n=90) underwent primary radical surgery including complete systematic pelvic lymph node (PLN) and para-aortic lymph node (PALN) adenectomy followed by adjuvant chemotherapy who were at risk for recurrence. Relapse-free survival (RFS) and disease-related survival (DRS) were analyzed using the log-rank testing. Multivariate Cox regression analysis and logistic regression analysis were used to determine and estimate independent prognostic factors. RESULTS: Lymph-vascular space invasion (LVSI), architectural grade (AG), myometrial invasion, and PLN metastasis (PLNM) were identified as independent prognostic factors for RFS. AG (p=0.0043) related with local recurrence. Among patients who received adjuvant chemotherapy, patients with G3 tumor had higher ratio of recurrence (16/45) compared with G1/2 tumor (11/102) (p=0.0004). Meanwhile, PLNM related with distant recurrence (p=0.0008). There was a statistically significant difference in RFS according to the number of positive PLN sites (group 0: n=313, 1: n=16, > or =2: n=26), five-year RFS in each group was 91.9%, 81.3%, and 41.2%, respectively. CONCLUSIONS: Sites of initial recurrence were related with AG and PLNM in patients with endometrioid uterine cancer. Current chemotherapy alone may not be an effective adjuvant therapy to prevent recurrence in patients with G3 tumor and > or =2 positive PLN sites. Prospective clinical trial needs to be conducted to establish the strategy of adjuvant therapy with these patients.

Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B(12) in pretreated Japanese patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with an Eastern Cooperative Oncology Group performance status 0 to 2, stage III or IV, and who received previously one or two chemotherapy regimens were randomized to receive 500 mg/m(2) pemetrexed (P500) or 1,000 mg/m(2) pemetrexed (P1000) on day 1 every 3 weeks. The primary endpoint was response rate. RESULTS: Of the 216 patients evaluable for efficacy (108 in each arm), response rates were 18.5% (90% confidence interval, 12.6-25.8%) and 14.8% (90% confidence interval, 9.5-21.6%), median survival times were 16.0 and 12.6 months, 1-year survival rates were 59.2% and 53.7%, and median progression-free survival were 3.0 and 2.5 months for the P500 and P1000, respectively. Cox multiple regression analysis indicated that pemetrexed dose was not a significant prognostic factor. Drug-related toxicity was generally tolerable for both doses; however, the safety profile of P500 showed generally milder toxicity. Main adverse drug reactions of severity grade 3 or 4 were neutrophil count decreased (20.2%) and alanine aminotransferase (glutamine pyruvic transaminase) increased (15.8%) in P500 and neutrophil count decreased (24.3%), WBC count decreased (20.7%), and lymphocyte count decreased (18.0%) in P1000. One drug-related death from interstitial lung disease occurred in the P500. CONCLUSION: P500 and P1000 are similarly active with promising efficacy and acceptable safety outcomes in pretreated patients with NSCLC. These results support the use of P500 as a second- and third-line treatment of NSCLC.

Role of complete para-aortic lymphadenectomy in endometrial cancer.

PURPOSE OF REVIEW: Many reports suggest the significance of pelvic lymph-node (PLN) adenectomy in patients with endometrial cancer. However, among these, there is controversy regarding not only what type of patients should have lymphadenectomy performed, but also what extent lymphadenectomy should be performed. RECENT FINDINGS: It has been reported that PLN adenectomy has therapeutic significance in stage I grade 3 and more advanced endometrioid uterine cancer. However, the effects of para-aortic lymph-node adenectomy on its prognostic benefit have not been discussed. SUMMARY: Patients with low-risk disease might not benefit from PLN adenectomy. However, PLN adenectomy might still have merit in low-risk patients, as there are inaccuracies of preoperative and intraoperative assessments. A complete lymphadenectomy is safe with minimum complications. At this point, hysterectomy and bilateral salpingo-oophorectomy with complete PLN adenectomy as the standard surgical procedure for endometrial cancer is thought to be reasonable. At present, the addition of p-aortic lymph-node adenectomy is regarded as an investigated protocol for endometrial cancer. However, p-aortic lymph-node adenectomy may have a therapeutic role for stage IIIC patients. Prospective randomized controlled trial composed of intermediate/high-risk patients should be conducted to clearly demonstrate prognostic improvement by p-aortic lymph-node adenectomy itself.

[Drug interactions in medical oncology].

Cytotoxic anti-neoplastic drugs are some of the strongest acting drugs. They have a complex pharmacological profile, narrow therapeutic window, steep dose-toxicity curve, and many pharmacokinetic and pharmacodynamic differences both within and between patients. This makes it difficult to avoid adverse effects. These drugs are approved for usage based on their clinical benefit to risk ratio. The recommended dose is usually close to the maximally-tolerated dose in order to achieve maximum therapeutic effect. Therefore, there is more concern about drug interactions affecting the pharmacokinetics of anti-neoplastic drugs than drugs in general. Any physician taking care of oncology patients must understand not only the pharmacokinetic profile(absorption, protein binding, metabolism and excretion)of the anti-neoplastic drugs their using, but also the many factors that affect the pharmacokinetic profile such as hepatic and renal function, and co-administered drugs. Expertise to achieve a good balance between safety and efficacy in medical treatment with proper knowledge in supportive care as well as an understanding of pharmacokinetics, pharmacodynamics and pharmacogenomics is essential for medical oncologists. In this review, we have summarized the drug-drug interactions important for the management of cancer patients. The types of interactions covered are pharmaceutical interactions and interactions at the level of absorption, protein binding, metabolism and excretion.

Laparoscopic posterior pelvic exenteration for primary adenocarcinoma of the rectovaginal septum without associated endometriosis: A case report.

The present report describes a case of laparoscopic posterior pelvic exenteration of a primary adenocarcinoma of the rectovaginal septum (PARS) without associated endometriosis. A 49-year-old woman was admitted to hospital for rectal bleeding. Imaging studies showed a 7-cm solid tumor located in the rectovaginal septum, presenting with invasion to the posterior aspect of the uterine cervix and the anterior rectal wall. The patient received laparoscopic posterior exenteration and rectosigmoid anastomosis followed by chemotherapy. There were no intra- or post-operative complications. Histopathological examination of the neoplastic tissue revealed moderate to severe cytological atypia with bizarre multinucleated cells and prominent mitotic figures. Histopathologically, R0 resection was achieved. No endometriotic lesions were confirmed in the primary tumor or other removed tissues. Immunohistochemistry showed positive staining for cytokeratin (CK)7, cancer antigen 125, vimentin, estrogen receptor and p53, but negative staining for CK20, progesterone receptor, p40 and thyroid transcription factor 1. Based on these findings and on the location of the tumor, the neoplasm was diagnosed as PARS without associated endometriosis, which may have arisen from metaplasia of the embryological Müllerian-duct remnants.

Incidental Finding of an Accessory Ovary at Laparoscopic Surgery.

An accessory ovary is one of the rare gynecologic abnormalities of the female genital tract. The etiology of accessory ovary has been reported to be acquired origin, such as postsurgical or postinflammatory implants, and true embryologic origin. However, as in the present case with unremarkable medical history and no urogenital abnormalities, there are accessory ovaries that cannot be explained by these etiologies. In such cases, the etiology of accessory ovary might possibly be torsion of functional ovarian cyst during the fetal period or asymptomatic torsion of the functional ovarian cyst at some time after birth.

[Influence of oral appliances for obstructive sleep apnea syndrome on stomatognathic system part 1. Occlusion].

PURPOSE: Little information is available on the mandibular protrusion with oral appliances (OA) for the treatment of obstructive sleep apnea syndrome (OSAS) to have no negative effect on the stomatognathic system. The purpose of the current study was to assess the influence of mandibular protrusion on occlusion to fabricate the appropriate OA. METHODS: Twelve healthy adults were selected. With the OA in position, the mandible was advanced 0, 45, 60, 75% of maximum protrusion capacity; bite raising distance between the first molars was 5mm (OA5-0, 45, 60 and 75). The occlusal force, occlusal contact area and occlusal load center following maximum voluntary clenching for 5 seconds were investigated as follows: after wearing the OA for 1, 3 and 6 hours (Stage A1, A3 and A6) and 1 hour after removal (Stage R1). These data were compared with before wearing (Stage B). RESULTS: Occlusal force has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, at Stages A3 and A6 after wearing OA5-60, and at Stage A6 after wearing OA5-0. Occlusal contact area has significant decrement at Stages A1, A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. Occlusal load center has significant forward displacement at Stages A3 and A6 after wearing OA5-75, and at Stage A6 after wearing OA5-60. CONCLUSION: To fabricate the appropriate OA in occlusal perspective, it is preferable to set the mandibular position at 45% advancement of maximum protrusion capacity of condyle head in terms of the mandibular positions used in this study.

Para-aortic lymphadenectomy may improve disease-related survival in patients with multipositive pelvic lymph node stage IIIc endometrial cancer.

OBJECTIVE: The purpose of this study was to determine whether para-aortic lymphadenectomy improves disease-related survival (DRS) in stage IIIc endometrial cancer. METHODS: A total of 63 patients with stage IIIc endometrial carcinoma underwent primary radical surgery in the Tohoku Gynecologic Cancer Unit from 1993 to 2004. All patients had modified radical hysterectomy, bilateral salpingo-oophorectomy, systemic pelvic lymph node (PLN) adenectomy, and with or without para-aortic lymph node (PAN) adenectomy, followed by adjuvant chemotherapy. DRS was analyzed using Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection. RESULTS: There were no statistical differences in age distribution and histopathological prognostic factors between PLN adenectomy group (n=25) and PLN+PAN adenectomy group (n=38). On univariate analysis, architectural grade (p=0.026), peritoneal cytology (p=0.033), and the number of PLN positive sites (/=2) (p=0.010) were related to poor DRS. On multivariate Cox regression analysis, the number of positive PLN sites was related to DRS (p=0.040). In positive PLN>/=2 sites group (n=33), PAN adenectomy significantly improved DRS compared to PLN adenectomy alone (p=0.011). The incidence of initial PAN recurrence was higher in the PLN adenectomy group (6/25) than in the PLN+PAN adenectomy group (1/38) (p=0.013, Odds Ratio=11.68). CONCLUSIONS: The number of positive PLN site is an independent prognostic factor in stage IIIc endometrial cancer. PAN adenectomy decreased the incidence of PAN recurrence and may improve DRS in patients with >/=2 positive PLN sites. A large prospective clinical trial needs to be conducted to establish the strategy of PAN adenectomy before or intra-operative treatment.

[Intrapulmonary bronchogenic cysts].

Bronchogenic cysts are commonly found in the mediastinum, but occasionally in lung parenchyma. We report 3 patients with intrapulmonary bronchogenic cysts. A female presented back pain and a large cystic lesion with an air-fluid level on chest X-ray and computed tomography (CT). Another female was asymptomatic. A well-defined round mass with soft tissue intensity on magnetic resonance imaging (MRI) was found. A girl with repeated pulmonary infection and treatment in hospital for several years presented pulmonary infiltrate, air-fluid level, and oval linear shadow on X-rays. All patients underwent lobectomy because of the size and the non-anatomical location of their lesions. Definite diagnosis on their lesions was determined by pathological study. Several small communications between the cyst and adjunctive parenchyma was found in the symptomatic girl, while the cyst was isolated from surrounding parenchyma in the asymptomatic female. We suggest symptoms and various presentations on imaging modalities in patients with intrapulmonary bronchogenic cysts might relate to the amount of original communication between their cysts and native lung.

START domain proteins and the intracellular trafficking of cholesterol in steroidogenic cells.

The intracellular trafficking of cholesterol in steroidogenic cells plays an important role in the regulation of hormone synthesis. Recent evidence indicates that a family of proteins related to the steroidogenic acute regulatory protein (StAR) perform critical functions in moving the sterol substrate to the mitochondrial inner membrane where the first committed step in steroid hormone synthesis occurs. StAR, the prototype of the family, is known to promote the translocation of cholesterol from the outer to the inner mitochondrial membrane. Mutations in StAR cause congenital lipoid adrenal hyperplasia, a cholesterol storage disorder in which synthesis of all gonadal and adrenocortical steroid hormones is severely impaired, and the cholesterol that is not efficiently moved into the mitochondria accumulates in cytoplasmic lipid droplets. The StAR-related lipid transfer (START) domain consists of an approximately 210 amino acid residue sequence that forms a compact alpha/beta structure, a helix-grip fold, with a hydrophobic tunnel that can accommodate a sterol molecule. START domains can bind sterol, facilitate the transfer of cholesterol from sterol-rich unilammelar liposomes to acceptor membranes, and stimulate steroidogenesis when expressed in cells co-expressing the cholesterol side-chain cleavage system or when added to isolated steroidogenic mitochondria. Sixteen human START domain proteins have been identified to date. Of these, StAR and MLN64 consist of one subfamily and newly described proteins named StarD4, StarD5, and StarD6 represent a closely related second subfamily. MLN64 is incorporated into the late endosomal compartment and is involved in the movement of cholesterol acquired from endocytosed LDL out of these vesicles. Expression of a dominant negative form of MLN64 causes accumulation of free cholesterol in lysosomes. The roles of StarD4, StarD5, and StarD6 in sterol movement remain to be determined. These genes have tissue-specific patterns of expression that may predict specialized roles.

Pathologic N1 non-small cell lung cancer: correlation between pattern of lymphatic spread and prognosis.

OBJECTIVES: Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. METHODS: From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%) had ipsilateral pulmonary lymph node metastases (N1). The hospital survivors (n = 535) were reviewed. Three levels of lymph node metastases (hilar, interlobar, and lobar) were identified according to the new Regional Lymph Node Classification for Lung Cancer Staging and differentiated from lymph node involvement on the basis of direct invasion. RESULTS: 1 The overall 5-year survival of patients with N1 disease was 40%. Survival was related in the univariate analysis to T classification, level-type of N1 involvement, number of involved nodes, multilevel involvement, Karnofsky Index, R status, and adjuvant therapy. In the multivariate analysis, only T classification and level-type of N1 involvement clearly showed statistical power (P =.000 and P =.001, respectively). The pattern of cancer relapse according to level-type of N1 involvement differed significantly: hilar N1 disease recurred at distant sites in 41% of patients and locoregionally in 12% of patients, whereas N1 disease by direct invasion occurred in 24% and 17% of patients, respectively (P =.030). CONCLUSIONS: Metastases to ipsilateral hilar, interlobar, or both, lymph nodes are associated with a poorer prognosis compared with metastases in intralobar lymph nodes or with lymph node involvement by means of direct invasion. Although surgical resection remains the mainstay of treatment, the high rate of tumor recurrence in both groups mandates further randomized studies with multimodality therapy approaches.

Operation for lung cancer in patients with idiopathic pulmonary fibrosis: surgical contraindication?

BACKGROUND: Patients with idiopathic pulmonary fibrosis have an increased incidence of lung cancer. The purpose of this study was to determine the outcome of surgical treatment of lung cancer with idiopathic pulmonary fibrosis. METHODS: From January 1992 through December 2001, 64 patients who had simultaneous lung cancer and idiopathic pulmonary fibrosis were treated. Twenty-one (33%) of them underwent surgical resection of lung cancer, and their data were reviewed. RESULTS: There were 56 men and 8 women with an average age of 69 years (range, 43 to 85 years). In the surgical group, there were no early postoperative deaths, and nonfatal complications occurred in 2 patients (10%). Among the 14 patients with stage I cancer, a second primary lung cancer developed in 5 (36%). The causes of death in the surgical group were cancer related in 7 patients, exacerbation of idiopathic pulmonary fibrosis in 7, and other in 2. Five of the 7 patients who died of a cancer-related cause had development of a second primary lung cancer. The actuarial 2-year survival rate of the surgical group was 52% overall, 58% for patients with N0 or N1 disease and 25% for those with N2 disease (p = 0.05). CONCLUSIONS: The long-term results in one surgical group were poor partly because of the high incidence of a second primary lung cancer and partly because of the poor natural history of idiopathic pulmonary fibrosis. These patients require intensive surveillance even after curative resection of lung cancer.

Lipopolysaccharide induces interleukin-8 production by human cervical smooth muscle cells.

OBJECTIVE: We examined the effect of lipopolysaccharide (LPS), a component of the outer wall of gram-negative bacteria, on expression of the neutrophil chemoattractant interleukin-8 (IL-8) and the effects of IL-8 treatment on release of matrix metabolizing enzymes in human cervical smooth muscle cells (CSMCs). METHODS: Human CSMCs were exposed to Escherichia coli LPS, and the expression of IL-8 mRNA was analyzed by Northern blotting. The IL-8 promoter activity was examined by dual luciferase assay, and the IL-8 concentration was assessed by enzyme-linked immunosorbent assay. We also treated the CSMCs with human IL-8 and examined the expression of matrix-degrading enzymes. RESULTS: E coli LPS (100 ng/mL) increased the expression of IL-8 mRNA 12.8-fold after 3 hours. This up-regulation was maintained for up to 24 hours. Lipopolysaccharide treatment produced a fivefold increase in IL-8 promoter activity in CSMCs transfected with an IL-8 promoter-reporter construct. IL-8 concentrations in conditioned medium of CSMC cultures treated with E coli LPS increased approximately 18-fold compared with the control cultures. Northern blot analysis and zymography revealed that exogenous human IL-8 had no significant effect on the expression of matrix metalloproteinase (MMP)-1, -3, and tissue inhibitor of metalloproteinase (TIMP)-1 mRNAs, and on the secretion MMP-2 and -9 in CSMCs. CONCLUSION: We conclude that CSMCs respond to LPS with increased expression of IL-8 mRNA and secreted IL-8, and that expression of matrix metabolizing enzymes in CSMCs is not directly affected by IL-8. IL-8 produced by CSMCs in response to gram-negative infection may promote neutrophil invasion, and release of neutrophil matrix-degrading enzymes may participate in the matrix remodeling associated with parturition.