Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies.

INTRODUCTION: This pooled analysis of nine phase I and II trastuzumab deruxtecan (T-DXd) monotherapy studies described drug-related interstitial lung disease (ILD)/pneumonitis in patients treated with T-DXd. METHODS: Patients who received T-DXd across nine studies were included. Investigator-assessed ILD/pneumonitis events were retrospectively reviewed by an independent adjudication committee; events adjudicated as drug-related ILD/pneumonitis are summarized. RESULTS: The analysis included 1150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%; other cancer, 3.0%). Median treatment duration was 5.8 (range, 0.7-56.3) months, with a median of 4 (range, 1-27) prior lines of therapy. The overall incidence of adjudicated drug-related ILD/pneumonitis was 15.4% (grade 5, 2.2%). Most patients with ILD/pneumonitis experienced low-grade events (grade 1 or 2, 77.4%); 87.0% had their first event within 12 months [median, 5.4 (range, <0.1-46.8) months] of their first dose of T-DXd. Based on data review, adjudicated ILD/pneumonitis onset occurred earlier than identified by investigators for 53.2% of events [median difference in onset date, 43 (range, 1-499) days]. Stepwise Cox regression identified several baseline factors potentially associated with increased risk of adjudicated drug-related ILD/pneumonitis: age <65 years, enrollment in Japan, T-DXd dose >6.4 mg/kg, oxygen saturation <95%, moderate/severe renal impairment, presence of lung comorbidities, and time since initial diagnosis >4 years. CONCLUSIONS: In this pooled analysis of heavily treated patients, the incidence of ILD/pneumonitis was 15.4%, with most being low grade and occurring in the first 12 months of treatment. The benefit-risk of T-DXd treatment is positive; however, some patients may be at increased risk of developing ILD/pneumonitis, and further investigation is needed to confirm ILD/pneumonitis risk factors. Close monitoring and proactive management of ILD/pneumonitis are warranted for all.

Evaluation and comparison of the diagnostic performance of routine blood tests in predicting liver fibrosis in chronic hepatitis B infection.

Background & aims: Biopsy is the gold standard for staging liver fibrosis, but it may be accompanied by complications. As an alternative, non-invasive markers such as transient elastography (for liver fibrosis) and certain combinations of routine blood markers (liver function tests, full blood count) have been developed although their clinical significance remains controversial. Here, we compare the diagnostic values of non-invasive markers for liver fibrosis in patients with chronic hepatitis B infection. Methods: Transient elastography and routine laboratory tests were performed in 196 patients. Diagnostic performances were compared and were assessed based on the area under the curve (AUC) of a receiver operating characteristic (ROC) analysis. Results: Elevated GGT to platelet ratio (GPR), the fibrosis index FIB-4 [based on age, AST, platelets and ALT], platelet to lymphocyte ratio (PLR) and total bilirubin were independent predictors of liver stiffness defined by transient elastography (all P < 0.001). The AUCs of GPR in predicting both advanced fibrosis and cirrhosis were significantly larger than that of FIB-4 (P = 0.037 and P = 0.008, respectively) and AST-to-platelet ratio index (APRI) (P = 0.008 and P = 0.005). FIB-4, APRI and red cell volume distribution width-to-platelet ratio (RPR) had similar diagnostic values in discriminating different levels of liver fibrosis. Conclusions: GPR showed the best diagnostic value and RPR and PLR are easily available and inexpensive markers in evaluating fibrosis and cirrhosis. The diagnostic values of these laboratory markers are useful in diagnosing advanced fibrosis or cirrhosis, and in confirming the different levels of liver fibrosis.

Complement activation in patients with diabetic nephropathy.

AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters. METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available. Seven complement components (C1q, MBL, Bb, C4d, C3a, C5a, soluble C5b-9) were measured by enzyme-linked immunosorbent assay (Elisa), and any associations between their levels and clinicopathological parameters were then investigated. RESULTS: In DN patients, plasma levels of C1q, MBL, Bb, C4d, C3a, C5a and sC5b-9 were significantly higher than in diabetes patients without renal involvement, as were also urinary levels except for C1q, which showed no significant differences between the two groups. Also, urinary levels of C3a and C5a were significantly correlated with serum creatinine, urinary protein and estimated glomerular filtration rate, whereas urinary sC5b-9 was significantly correlated with the latter two (and not serum creatinine). In addition, urinary levels of MBL, Bb and C4d were significantly correlated with urinary protein, while C3a, C4d and Bb significantly correlated with the classification of glomerular lesions in DN. CONCLUSION: In DN patients, the complement system is activated and, of the three possible complement pathways, activation of the lectin and alternative pathways is associated with renal damage.

Complement deposition on renal histopathology of patients with diabetic nephropathy.

AIMS: As the potential role of the complement system in diabetic nephropathy (DN) is increasingly reported, this study aimed to investigate C1q and C3c deposition as seen on renal histopathology, as well as its association with clinical and pathological parameters, in DN patients. METHODS: Renal biopsy specimens from 161 DN patients were investigated using direct immunofluorescence, light, and electron microscopy. For direct immunofluorescence, staining for C1q and C3c on fresh-frozen renal tissue was performed immediately after biopsy. Complement deposition was defined as the presence of C1q or C3c of at least 1 + on a 0-4 + Scale. The association between complement deposition and clinicopathological data was also analyzed. RESULTS: On direct immunofluorescence microscopy, C1q and C3c were detected in specimens from 44/161 (27.3%) and 89/161 (55.3%) patients, respectively. Regarding clinical data, patients with C1q deposition had a significantly higher level of urinary protein (7.25 ± 4.20 g/24 h vs. 4.97 ± 3.76 g/24 h; P < 0.01) and significantly lower estimated glomerular filtration rate (eGFR; 34.16 ± 25.21 mL/min/1.73 m2 vs. 51.17 ± 31.56 mL/min/1.73 m2, respectively; P < 0.01), whereas patients with vs. without C3c deposition had a significantly lower eGFR (40.09 ± 27.97 mL/min/1.73 m2 vs. 54.48 ± 32.49 mL/min/1.73 m2, respectively; P < 0.01). On renal histopathology, patients with C1q deposition had significantly higher Scores for interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and vascular lesions (P < 0.01, P < 0.05 and P < 0.05, respectively), whereas patients with C3c deposition had significantly higher IFTA Scores and proportions of global sclerosis (P < 0.01 and P < 0.01, respectively). CONCLUSION: Complement deposition of C1q and C3c on renal histopathology is associated with more severe kidney damage in patients with DN.

Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model.

BACKGROUND: Since the recent establishment of a murine model of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), both the development of new drugs for treatment or prevention of eosinophilic CRSwNP and elucidation of their pathogenesis have been feasible. We investigated the therapeutic effects of resveratrol on CRSwNP and its mechanism of action using a murine model. METHODS: After induction of eosinophilic CRSwNP, the therapeutic effects of resveratrol were tested and compared with those of triamcinolone acetonide. Histopathologic changes were evaluated using hematoxylin and eosin for overall inflammation, Sirius red for eosinophils, and Masson's trichrome stain for collagen. The expression levels of the interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were assessed by quantitative real-time PCR. Cyclooxygense-2 and 5-lipoxygense levels were evaluated by immunohistochemical staining and Western blot analysis. RESULTS: The degree of eosinophilic infiltration and subepithelial fibrosis was significantly decreased by administration of high-dose resveratrol, the potency of which was similar to that of triamcinolone acetonide. The expression levels of the IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase genes were significantly decreased by administration of low- or high-dose resveratrol. The production of 5-lipoxygenase was strongly inhibited by high-dose resveratrol. CONCLUSIONS: Resveratrol may be useful for the prevention of eosinophilic CRSwNP. A key mechanism of its action is believed to be its anti-inflammatory effect, particularly on eosinophils, by inhibiting the lipoxygenase pathway.

Distant metastasis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) relapses more frequently than hormone receptor-positive subtypes and is often associated with poor outcomes. This retrospective study reviewed the pattern of distant metastasis with regard to survival in patients with TNBC. A total of 205 TNBC patients were analyzed. TNBC patients with lung metastases had the longest median post-metastatic OS (with 95% confidence interval) of 16.6 (10.3-22.9) months, followed by the bone, 16.3 (11.7-20.8) months, the liver, 8.9 (3.5-14.4) months, the pleura, 7.5 (2.8-12.3) months, and the brain, 4.3 (0.6-8.0) months. Kaplan-Meier plots indicated that TNBC patients with metastatic spread to brain, liver, and pleural had poorer post-metastatic OS rate than patients with lung metastases (p = 0.001, 0.004, and 0.029, respectively). Moreover, brain and liver metastases correlated significantly with poorer post-metastatic OS as compared to bone metastasis (p = 0.004 and 0.011, respectively). Route of first metastasis correlated significantly with survival of TNBC patients with brain metastases being the poorest survival indicator, followed by metastases to liver, pleura, bone, and lung.

Changes in uterine blood flow following laparoscopic myomectomy with or without uterine artery ligation on two- and three-dimensional power Doppler ultrasound.

OBJECTIVE: To evaluate differences in uterine perfusion following laparoscopic myomectomy with or without uterine artery ligation (UAL). METHODS: From November 2005 to July 2007, we enrolled prospectively 105 women with symptomatic myomas who were scheduled to undergo laparoscopic myomectomy (57 with UAL (study group) and 48 without (control group)). Power Doppler ultrasound was used to evaluate uterine artery resistance (RI) and pulsatility (PI) indices and peak systolic velocity (PSV) and three-dimensional (3D) power Doppler ultrasound was used to obtain vascularization (VI), flow (FI) and vascularization flow (VFI) indices of the uterine tissue, which were calculated by VOCAL (Virtual Organ Computer-aided AnaLysis) software. RESULTS: Characteristics of the myomas, operative time and duration of hospital stay were comparable between the two groups, whereas the median (range) of estimated blood loss (50 (50-200) vs. 100 (50-900) mL, P = 0.001) and the frequency of excessive bleeding of > 500 mL (0% vs. 10%, P = 0.018) were significantly lower in the study group. The RI, PI and PSV were comparable between the two groups preoperatively, significantly lower in the study group 1 week after surgery (0.69 vs. 0.74, 1.31 vs. 1.76, and 34.08 vs. 47.49, respectively, P < 0.05), and comparable again 3 months later. The myometrial VI and VFI decreased after surgery and all three 3D power Doppler indices of the study group were similar to those of the control group throughout the study period. CONCLUSION: Concurrent UAL during laparoscopic myom- ectomy reduces the intraoperative blood loss and frequency of excessive bleeding without permanently compromising uterine perfusion.

Minimizing bladder injury in laparoscopically assisted vaginal hysterectomy among women with previous cesarean sections.

BACKGROUND: This study demonstrated a method to prevent bladder injury during laparoscopically assisted vaginal hysterectomy (LAVH) to patients with vesicocervical adhesion after previous cesarean deliveries. METHODS: Between July 2004 and July 2005, 50 women with vesicocervical adhesion who had given birth by cesarean delivery underwent LAVH. To minimize the chance of bladder injury, transvaginal lateral intervention was used to enter the anterior cul-de-sac during laparoscopic intrafascial hysterectomy. The lateral windows of the vesicocervical space were opened first. Usually, the potential spaces lateral to the adhesions could be developed easily by blunt finger dissection. Once adequate lateral spaces were created, an index finger was swept medially to define the margin of the midline adhesions secondary to the cesarean delivery scar. Under direct vision and finger guidance, the dense adhesions were dissected with more confidence and safety. Subsequently, the bladder was pushed gently aside to avert unexpected tearing or injury along the intrafascial hysterectomy. Because the vesico-uterine fold had been cut open previously under laparoscopy, the anterior cul-de-sac could be entered without much resistance. RESULTS: The average age of the patients was 45 +/- 7 years, and the extirpated uterine weight was 323 +/- 170.8 g (range, 85-730 g). Intraoperatively, the mean operation time was 124.6 +/- 28.5 min (range, 80-235 min), and the average blood loss was 79.1 +/- 47.8 ml (range, 20-250 ml). The mean intramuscular meperidine requirements were 1.2 +/- 0.8 ampules (range, 0-2 ampules) (1 ampule = 50 mg), and the average hospital stay was 3.2 +/- 0.9 days (range, 2-5 days). Of these 50 patients, 24 (48%) had one, 22 (44%) had two, and 4 (8%) had three previous cesarean deliveries. No bladder injury occurred among the patients, and there was no other complication. CONCLUSION: Transvaginal lateral intervention may help to minimize bladder injuries during LAVH for patients with previous cesarean deliveries.

Expression of inhibitory natural killer receptors on tumor-infiltrating CD8+ T lymphocyte lineage in human endometrial carcinoma.

To investigate the expression of natural killer receptors (NKRs) within the human tumor milieu, we directly examined the in vivo expressions of various NKRs on tumor-infiltrating lymphocytes (TILs) derived from human endometrial carcinoma (EC). In total, 22 patients with stage IA-IIIA EC were enrolled. TILs were isolated from tissue specimens by means of a mechanical dispersal technique. The subpopulations of immunocytes were quantified, and expressions of NKRs on CD8+ T cells were analyzed by triple-color flow cytometry. CD8+ T cells express higher ratios of CD94 and NKG2A in TILs than in peripheral blood mononuclear cells (PBMCs) in human EC. Flow cytometry reveals that 15.90% of CD3+CD8+ TILs compared with 2.10% of CD3+CD8+ PBMCs express the NKG2A molecules (P < 0.001). The percentage expressions of CD94 are 8.40% in CD3+CD8+ TILs and 3.80% in CD3+CD8+ PBMCs (P= 0.013). The numbers of CD8+ T cells expressing CD158b and NKB1 are higher in CD3+CD8+ PBMCs in EC than in normal (CD158b: 10.70% vs 2.60%, P < 0.001; NKB1: 2.20% vs 0.40%, P= 0.018, respectively). Increased expression of CD94/NKG2A restricted to tumor-infiltrating CD8+ T cell subsets may shape the cytotoxic responses, which indicate a possible role of tumor escape from host immunity in human EC.

Repair of oxidative DNA damage: mechanisms and functions.

Cellular genomes suffer extensive damage from exogenous agents and reactive oxygen species formed during normal metabolism. The MutT homologs (MutT/MTH) remove oxidized nucleotide precursors so that they cannot be incorporated into DNA during replication. Among many repair pathways, the base excision repair (BER) pathway is the most important cellular protection mechanism responding to oxidative DNA damage. The 8-oxoG glycosylases (Fpg or MutM/OGG) and the MutY homologs (MutY/MYH) glycosylases along with MutT/MTH protect cells from the mutagenic effects of 8-oxoG, the most stable and deleterious product known caused by oxidative damage to DNA. The key enzymes in the BER process are DNA glycosylases, which remove different damaged bases by cleavage of the N-glycosylic bonds between the bases and the deoxyribose moieties of the nucleotide residues. Biochemical and structural studies have demonstrated the substrate recognition and reaction mechanism of BER enzymes. Cocrystal structures of several glycosylases show that the substrate base flips out of the sharply bent DNA helix and the minor groove is widened to be accessed by the glycosylases. To complete the repair after glycosylase action, the apurinic/apyrimidinic (AP) site is further processed by an incision step, DNA synthesis, an excision step, and DNA ligation through two alternative pathways. The short-patch BER (1-nucleotide patch size) and long-patch BER (2-6-nucleotide patch size) pathways need AP endonuclease to generate a 3' hydroxyl group but require different sets of enzymes for DNA synthesis and ligation. Protein-protein interactions have been reported among the enzymes involved in BER. It is possible that the successive players in the repair pathway are assembled in a complex to perform concerted actions. The BER pathways are proposed to protect cells and organisms from mutagenesis and carcinogenesis.

Prognostic factors of primary adenocarcinoma of the uterine cervix.

OBJECTIVE: To determine which clinicopathological factors influence the prognosis of cervical adenocarcinoma. METHODS: Three hundred and two cases of primary adenocarcinoma of the uterine cervix, treated between 1977 and 1994, were studied retrospectively. Clinical data and pathological findings with respect to primary therapy were reviewed and evaluated. RESULTS: The 5-year survival rates for stages I, II, and III/IV were 75.9, 62.9, and 25.1%, respectively. International Federation of Gynecology and Obstetrics stage (P < 0. 0001), cell type (P = 0.0176), tumor grade (P = 0.023), lymph node status (P = 0.018), and bulky tumor (P = 0.007) were found to be independent factors using the stepwise Cox proportional hazards model. Old age (P = 0.0581), presence of hypertension (P = 0.46), diabetes mellitus (P = 0.18), obesity (P = 0.15), and oral contraceptive use (P = 0.42) were not found to adversely influence survival rates for cervical adenocarcinoma after adjusting for other covariates. Adenosquamous adenocarcinoma had a better prognosis than endocervical columnar cell adenocarcinoma in stages I and II (P = 0. 0235). Also, in cervical adenocarcinoma's early stages, multivariate modeling revealed that chances of survival were significantly better for patients treated by radical surgery than for patients treated by radiation therapy (P < 0.001). CONCLUSIONS: Survival rates for cervical adenocarcinoma were significantly influenced by stage, histologic subtype, tumor grade, the presence of a positive lymph node, and tumor size. Although a randomized prospective study is needed, our data imply that radical surgery may be considered a better primary modality of treatment than radiation therapy for the early stages of cervical adenocarcinoma. Further, the presence of hypertension, diabetes mellitus, or obesity may not adversely influence survival rates.

The potential of serum levels of soluble tumour necrosis factor receptor I as a biochemical marker in cervical cancer.

OBJECTIVES: To investigate the significance of serum levels of soluble tumour necrosis factor receptor I (sTNF-RI) as a potential biochemical marker in women with cervical cancer. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-one women with cervical cancer and 33 women with myoma were enrolled in this study. METHODS: Pre-operative serum levels of sTNF-RI were measured with a standard enzyme-linked immunosorbent assay utilising murine monoclonal antibody against sTNF-RI. MAIN OUTCOME MEASURES: All data in both groups were evaluated and correlated with the pre-operative serum levels of sTNF-RI. Data analysis was carried out using ANOVA with multiple comparison and linear regression. RESULTS: The mean serum level of sTNF-RI in the cervical cancer group was significantly lower than that in the myoma group (P < 0.001). The sTNF-RI levels decreased sequentially with disease progression from Stage Ia to IIb in women with cervical cancer. The mean serum level of sTNF-RI was also significantly lower in women with positive lymph node (P < 0.05) or recurrent cancer (P < 0.001). A negative correlation was observed between serum levels of sTNF-RI and tumour size (r = -0.622, P < 0.0001). CONCLUSIONS: Decreased pre-operative serum levels of sTNF-RI are observed in women with cervical cancer. The results do not support that the use of sTNF-RI as a biochemical marker for cervical cancer.

A highly conserved nucleotide in the Alu domain of SRP RNA mediates translation arrest through high affinity binding to SRP9/14.

Binding of the signal recognition particle (SRP) to signal sequences during translation leads to an inhibition of polypeptide elongation known as translation arrest. The arrest activity is mediated by a discrete domain comprised of the Alu portion of SRP RNA and a 9 and 14 kDa polypeptide heterodimer (SRP9/14). Although very few nucleotides in SRP RNA are conserved throughout evolution, the remarkable conservation of G24, which resides in the region of SRP9/14 interaction, suggests that it is essential for translation arrest. To understand the functional significance of the G24 residue, we made single base substitutions in SRP RNA at this position and analyzed the ability of the mutants to bind SRP9/14 and to reconstitute functional SRPs. Mutation of G24 to C reduced binding to SRP9/14 by at least 50-fold, whereas mutation to A and U reduced binding approximately 2- and 5-fold respectively. The mutant RNAs could nevertheless assemble into SRPs at high subunit concentrations. SRPs reconstituted with mutant RNAs were not significantly defective in translation arrest assays, indicating that the conserved guanosine does not interact directly with the translational machinery. Taken together, these results demonstrate that G24 plays an important role in the translation arrest function of SRP by mediating high affinity binding of SRP9/14.

Adenomyosis in the broad ligament and tamoxifen: report of a case.

Adenomyosis confined to the broad ligament is extremely rare. Herein we present a case of adenomyosis in the broad ligament with unusual gross features. This 41-year-old woman had been on tamoxifen therapy for 3 years due to breast cancer. Ten months after discontinuing tamoxifen, she underwent exploratory laparotomy for a right adnexal mass suspected as ovarian malignancy. At laparotomy, the mass was located in the right broad ligament with a fibrous stalk connecting to the uterus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathologic examination revealed adenomyosis with cyst formation and an unusual thick capsule. The possible effects of tamoxifen upon the uterus are discussed in this article, in view of reports of tamoxifen associated with endometrial carcinoma and endometriosis.

Prevalence of single and multiple infection with human papillomaviruses in various grades of cervical neoplasia.

Evaluation of human papillomavirus (HPV) diversity in various grades of cervical lesions is helpful for understanding the characteristics of HPV infection in the pathogenesis of cervical neoplasia. A total of 227 women with normal cervices (n = 72), low- and high-grade cervical squamous intraepithelial lesions (SILs) (n = 55 and 53, respectively) and cervical carcinomas (n = 47) were screened for human papillomavirus (HPV) types 6, 11, 16 and 18 infection by the polymerase chain reaction. The prevalence of multiple HPV infections in patients with normal cervices, low-grade SILs, high-grade SILs and cervical carcinomas was 22.2%, 61.8%, 41.5% and 21.3%, respectively, while the prevalence of a single-type infection was 36.1%, 21.8%, 30.2% and 61.7%, respectively. HPV 16/11 and 16/18 were the most common combinations observed in multiple infections. Multiple HPV infections were seen most frequently in patients with low-grade SILs, and the prevalence decreased with increasing severity of cervical neoplasia. In contrast, infection with a single HPV type was most commonly observed in patients with cervical carcinoma, and the prevalence decreased with decreasing severity of cervical neoplasia. HPV 16 was the predominant single-type infection in patients with cervical carcinoma and this prevalence decreased steadily with decreasing severity of cervical neoplasia. Conversely, HPV 11 was the predominant single-type infection in patients with normal cervices. This prevalence decreased with increasing severity of cervical neoplasia. Patients with low-grade SILs had a higher prevalence of HPVs, regardless of single or multiple infection status, and larger copy numbers of virus genome were seen more frequently in patients with more severe lesions.

Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells.

Nearly 1 000 000 copies of Alu interspersed elements comprise approximately 5% of human DNA. Alu elements cause gene disruptions by a process known as retrotransposition, in which dimeric Alu RNA is a presumed intermediate. Dimeric Alu transcripts are labile, giving rise to stable left monomeric scAlu RNAs whose levels are tightly regulated. Induction of Alu RNA by viral infection or cell stress leads to a dramatic increase in dimeric Alu transcripts, while scAlu RNA increases modestly. Each monomer of the dimeric Alu element shares sequence homology with the 7SL RNA component of the signal recognition particle (SRP). The SRP protein known as SRP9/14 is also found in a discrete complex with scAlu RNA, although whether dimeric Alu RNA is associated with SRP9/14 had been unknown. Here we show that antiserum to human SRP9 immunoprecipitates both scAlu RNA and dimeric Alu RNAs and that these RNPs accumulate after adenovirus infection, while levels of SRP9, SRP14, SRP54 and 7SL SRP RNA are unaffected. Dimeric Alu RNAs are also associated with the La protein, indicating that these are indeed nascent RNA polymerase III transcripts. This report documents that induced Alu transcripts are assembled into SRP9/14-containing RNPs in vivo while SRP levels are unchanged. Implications for Alu RNA metabolism and evolution are discussed.

Prediction of residual neoplasia based on histopathology and margin status of conization specimens.

OBJECTIVE: To evaluate the status of cone margins and the severity of cervical neoplasia as predictors of residual lesions in the remaining cervices. METHODS: We performed a 7-year retrospective study and reviewed 172 patients who had undergone cervical conization followed by subsequent hysterectomy. Pathological findings of the cone margins and residual lesions in the postcone hysterectomy specimens were recorded for analysis. RESULTS: The prevalence rates of positive cone margins were 0, 18.6, 23.8, and 25%, respectively, in patients with low-grade squamous intraepithelial lesion (SIL) (n = 6), high-grade SIL (n = 129), stage IA1 cervical cancer (CC-IA1) (n = 21), and CC-IA2 (n = 16). The prevalence rates of positive residual lesions in postcone hysterectomy specimens were 0, 23.3, 23.8, and 43.8%, respectively, in those with low-grade SIL, high-grade SIL, CC-IA1, and CC-IA2. Residual lesions were significantly more frequently found in patients with positive cone margins (84.8%) than in those with negative margins (10.1%) (X2 = 76.81, P < 0.0001). All six patients with low-grade SIL had free cone margins. Positive predictive values of margin status for the presence of residual lesions were 83.3, 80, and 100%, respectively, in patients with high-grade SIL, CC-IA1, and CC-IA2. Only two (6.1%) of 33 patients with positive cone margins had more advanced residual lesions. Negative predictive values of margin status for the absence of residual lesions were 100, 90.5, 93.8, and 75%, respectively, in patients with low-grade SIL, high-grade SIL, CC-IA1, and CC-IA2. None of the 139 patients with negative margins had invasive residual lesion. CONCLUSIONS: (1) The prevalence of positive cone margin and residual lesion increased with higher severity of cervical neoplasia. (2) Patients with positive cone margins had significantly higher chances of having residual lesion than those with negative margins. (3) Free cone margin does not ensure the absence of residual lesion in the remaining cervix. However, the possibility of residual invasive cancer in the remaining cervix is remote. (4) Positive cone margin does not invariably indicate the presence and persistence of more severe residual lesion. Subsequent hysterectomy may be reserved for the patient with invasive cone pathology, the patient with concomitant morbid uterine condition, or the patient who is not reliable for continuous follow-up.

Mature cystic teratoma of the ovary: a clinicopathologic study of 283 cases.

BACKGROUND: Although in the English literature, much has been published about ovarian teratoma, no large series has been reported in Taiwan. Therefore a retrospective study of 283 consecutive cases of mature cystic teratomas of the ovary, operated at National Taiwan University Hospital between 1988 and 1993, was undertaken. METHODS: This series was based on a retrospective chart study at the Department of Obstetrics and Gynecology of the National Taiwan University Hospital from 1988 to 1993. All cases included in this study were proven by pathology review. The clinical data, pathology and complications are summarized. RESULTS: The incidence of mature cystic teratoma was 32.6% of primary ovarian neoplasm. As for the age distribution, the youngest patient was 12 years old and the oldest, 76. The largest number of cases was found in patients between the ages of 20 and 30 years; the mean age was 35.4 years. Pain, the most common complaint, was noted in 48.1% of the cases in whom it varied from a dull ache to the sharp, stabbing pain of torsion. Of greater interest was an unexpectedly high incidence (16.6%) of asymptomatic cysts found on routine physical examination. The right ovary was involved in 51.2%, the left ovary in 40.6% and bilateral ovaries were involved in 8.2%. The incidence of torsion was 9.2%, and was the highest in all complications. Ten concurrent pregnancies were noted, an incidence of 3.5%. The incidence of malignant transformation was 0.7%, with a pathology of squamous cell carcinoma. CONCLUSIONS: Mature cystic teratom is the most common germ cell tumor and accounts for about 33% of all ovarian neoplasm They occur primarily during the reproductive years, but may occur in the postmenopausal period or in childhood. A cystic teratoma can undergo malignant transformation; it occurs most frequently in postmenopausal women, and the prognosis is poor. However, it is a rare complicaiton, with an incidence less than 1%.

The suitable treatment for adenocarcinoma in situ of uterine cervix: a report of four cases.

Adenocarcinoma in situ (AIS) of the uterine cervix is a rare disease. Some authors suggested that conization is a suitable treatment for AIS as for squamous cell carcinoma in situ. However, others did not agree. Four cases of AIS, from 1984 to 1994, have been diagnosed in the Hospital of National Taiwan University. If the diagnosis of the conization specimen showed AIS, abdominal total hysterectomy was performed days thereafter. The remaining uterine cervix was checked by histopathology to determine whether it was free of cancer lesions. AIS lesions remained in the uterine cervix, as shown by conization in two cases. AIS is not like lesion as squamous cell carcinoma in situ lesion which is easy to be removed by conization. It is suggested that conization is not an adequate treatment for AIS, rather, a total hysterectomy should be performed.