Value of Second Pass in Loop Electrosurgical Excisional Procedure

The aim of this study was to compare the rate of incomplete resection and treatment outcome of the second-pass technique with those of single-pass technique in loop electrosurgical excisional procedure (LEEP). From 1997 to 2002, 683 women were diagnosed as squamous dysplasia via LEEP in our institution. Age, parity, LEEP technique, grade of lesion, glandular extension, margin status, residual tumor and recurrence were obtained by reviewing medical records. Positive margin was defined as mild dysplasia or higher grade lesions at resection margin of the LEEP specimen. In women who underwent hysterectomy, residual tumor was defined as mild dysplasia or higher grade lesions in hysterectomy specimen. In women who did not underwent hysterectomy, Pap smear more than atypical squamous cells of undetermined significance or biopsy result more than mild dysplasia within two years after LEEP were regarded as cytologic or histologic recurrences, respectively. Treatment failure of LEEP was defined as residual tumor or histologic recurrence. The second-pass technique significantly reduced the endocervical margin positivity (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.21-0.63). However, the second-pass technique did not reduce the treatment failure (OR, 0.62; 95% CI, 0.29-1.32). In conclusion, the second-pass technique markedly reduced the endocervical margin positivity, but did not reduce the treatment failure rate of LEEP

XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer

OBJECTIVE: The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of genes which are involved in DNA synthesis and repair with the response to platinum-based neoadjuvant chemotherapy (NAC) and disease-free survival (DFS) in patients with cervical cancer who were treated with NAC followed by radical hysterectomy. METHODS: A retrospective review was performed on 66 patients with cervical cancer who were treated with NAC followed by radical hysterectomy in our institute between January 1999 and February 2007. DNA was extracted from the paraffin-embedded, formalin-fixed tissue blocks of hysterectomy specimens. The genotypes of SNPs (MTHFR 677Cytosine/Thymine, XRCC1 Arginine194Tryptophan, GGH-401Cytosine/Thymine, and GSTP1 Isoleucine105Valine) were determined using a single base primer extension assay. The association of SNP genotypes with the response to NAC, which was measured by physical and colposcopic examinations, was evaluated. In addition, DFS based on SNP genotypes was examined. RESULTS: The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.023 for XRCC1 Arginine194Tryptophan; P=0.046 for GGH-401Cytosine/Thymine). However, the genotypes of MTHFR 677Cytosine/Thymine and GSTP1 Isoleucine105Valine were not associated with the response to NAC. In subgroup analysis with 39 patients who were treated with regimens containing 5-fluorouracil (5-FU), the genotypes of GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.039). In multifactor dimensionality reduction (MDR) analysis, the combination of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine genotypes was associated with the response to NAC (P<0.001). However, no SNP genotypes were associated with DFS, but the cisplatin dose intensity of NAC was associated with DFS. CONCLUSIONS: The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were associated with the response to NAC in patients with cervical cancer. However, no SNP genotypes were associated with DFS.This work was supported by grant 04-2006-040 from the Seoul National University Hospital Research Fund

Impact of Underweight after Treatment on Prognosis of Advanced-Stage Ovarian Cancer

This study aimed to investigate the impact of underweight status on the prognosis of advanced-stage ovarian cancer. A total of 360 patients with stage III-IV epithelial ovarian cancer were enrolled and divided into three groups by body mass indexes (BMIs): underweight (BMI < 18.5 kg/m2); normal weight to overweight (18.5 kg/m2 BMI < 27.5 kg/m2); obesity (BMI ≥ 27.5 kg/m2). Progression-free survival (PFS), overall survival (OS), CA-125, and neutrophil to lymphocyte ratio (NLR) as a marker reflecting host inflammation and immunity were compared among the three groups according to the three treatment times: at diagnosis; after surgery; and after treatment. Only underweight status after treatment was associated with poor OS in comparison with normal weight to overweight or obesity (mean value, 44.9 versus 78.8 or 67.4 months; P=0.05); it was also an unfavorable factor for OS (adjusted HR, 2.29; 95% CI, 1.08–4.85). Furthermore, NLR was higher in patients with underweight than in those with obesity after treatment (median value, 2.15 versus 1.47; P=0.03), in spite of no difference in CA-125 among the three groups at the three treatment times. In conclusion, underweight status after treatment may be a poor prognostic factor in patients with advanced-stage ovarian cancer, which accompanies increased host inflammation and decreased immunity

Inadvertent potential risk of neoadjuvant chemotherapy in cervical cancer

Randomized clinical trials comparing neoadjuvant chemotherapy (NAC) followed by surgery with initial surgery in cervical cancer reported conflicting results. We provided a hypothesis explaining the different outcomes between trials. NAC was reported to make a lymph node metastasis smaller. Smaller tumors are hard to detect and potentially undetected at pathologic examination. Undetected metastasis would lead to an erroneous exclusion of high-risk patients from adjuvant therapy. An erroneous exclusion would lead to a recurrence. This harmful concealing effect of NAC could negate the potentially beneficial effect of NAC and the conflicting results of trials could be the result of the balance between harmful and beneficial effect of NAC. Because the concealing effect of NAC can be reversed by adjuvant therapy, trials comparing NAC followed by surgery with initial surgery in which all patients in both arms received adjuvant therapy reported positive result. However, in a trial in which only patients with lymph node or parametrial involvements received adjuvant therapy, the concealing effect was not reversed by adjuvant therapy and reported negative result. Our empirical data showed that patients who underwent NAC followed by surgery and were classified as low-risk based on pathologic parameters had unexpectedly high recurrence rate. To evaluate our hypothesis, a trial comparing a conventional pathologic examination with a more sophisticated examination such as ultrastaging in patients with cervical cancer who received NAC followed by surgery would be necessary. If our hypothesis is proven, trials considering the concealing effect of NAC should be performed to accurately evaluate the role of NAC in cervical cancer. (C) 2009 Elsevier Ltd. All rights reserved.Taucher S, 2008, BREAST CANCER RES TR, V112, P309, DOI 10.1007/s10549-007-9844-9Chen HJ, 2008, GYNECOL ONCOL, V110, P308, DOI 10.1016/j.ygyno.2008.05.026Horn LC, 2007, GYNECOL ONCOL, V107, P310, DOI 10.1016/j.ygyno.2007.06.026Eddy GL, 2007, GYNECOL ONCOL, V106, P362, DOI 10.1016/j.ygyno.2007.04.007Bader AA, 2007, AM J SURG, V194, P135, DOI 10.1016/j.amjsurg.2006.05.017Bader AA, 2006, GYNECOL ONCOL, V103, P106, DOI 10.1016/j.ygyno.2006.01.051Cai HB, 2006, J OBSTET GYNAECOL RE, V32, P315, DOI 10.1111/j.1447-0756.2006.00404.xKinoshita T, 2006, AM J SURG, V191, P225, DOI 10.1016/j.amjsurg.2005.06.049Benedetti-Panici P, 2003, EUR J CANCER, V39, P2470, DOI 10.1016/S0959-8049(03)00425-8NAPOLITANO U, 2003, EUR J GYNAECOL ONCOL, V24, P51Baslaim MM, 2002, AM J SURG, V184, P299Sardi JE, 1998, INT J GYNECOL CANCER, V8, P441Sardi JE, 1997, GYNECOL ONCOL, V67, P61SEVIN BU, 1995, CANCER, V76, P1978

Matched-case comparison for the efficacy of neoadjuvant chemotherapy before surgery in FIGO stage IB1-IIA cervical cancer

Objective. To evaluate whether neoadjuvant chemotherapy before surgery (NCS) is more efficient than primary surgical treatment (PST) for improving clinical outcomes in FIGO stage IB1-IIA cervical cancer. Methods. We conducted a matched-case comparison where 61 patients treated with NCS were matched to 183 treated with PST. We compared intermediate- and high-risk factors, the need of adjuvant radiotherapy, disease recurrence and survivals between NCS and PST. Patients with >= 2 intermediate- or >= 1 high-risk factors received adjuvant concurrent chemoradiation using cisplatin-based chemotherapy. Results. NCS reduced more definitely intermediate- and high-risk factors than PST in stage IIA disease in spite of little difference of them in stage IB disease (large tumor size, 25% vs. 52.4%; deep stromal invasion, 57.1% vs. 82.1%; lymphovascular space invasion, 35.7% vs. 65.5%; parametrial invasion, 17.9% vs. 41.7%; p= 2 intermediate-risk factors were less common in NCS than PST despite no difference of the number of high-risk factors between the 2 treatments, which decreased the need of adjuvant radiotherapy in patients with stage IIA disease who received NCS (46.4% vs. 84.5%, p<0.01). Although there were no differences in progression-free survival and disease recurrence between the 2 treatments, NCS led to poorer overall survival than PST in stage IIA disease with no difference of it in stage IB disease. Conclusions. The efficacy between NCS and PST may be similar in FIGO stage IB cervical cancer. However, NCS can lead to poor prognosis despite the reduction of intermediate-risk factors and the need of adjuvant radiotherapy in FIGO stage IIA disease. (C) 2010 Elsevier Inc. All rights reserved.Rydzewska L, 2010, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD007406.pub2Kim K, 2009, MED HYPOTHESES, V73, P1005, DOI 10.1016/j.mehy.2009.05.026Kim K, 2009, J GYNECOL ONCOL, V20, P203, DOI 10.3802/jgo.2009.20.4.203Chen HJ, 2008, GYNECOL ONCOL, V110, P308, DOI 10.1016/j.ygyno.2008.05.026Eddy GL, 2007, GYNECOL ONCOL, V106, P362, DOI 10.1016/j.ygyno.2007.04.007Kang SB, 2006, CANCER LETT, V237, P305, DOI 10.1016/j.canlet.2005.06.027Cai HB, 2006, J OBSTET GYNAECOL RE, V32, P315, DOI 10.1111/j.1447-0756.2006.00404.x*WHO, 2006, WHO REP COMPR CERV CKATSUMATA N, 2006, P AM SOC CLIN ONCOLO, V24Buda A, 2005, J CLIN ONCOL, V23, P4137, DOI 10.1200/JCO.2005.04.1722003, EUR J CANC, V39, P2470Benedetti-Panici PL, 2003, EUR J GYNAECOL ONCOL, V24, P467Napolitano C, 2003, EUR J GYNAECOL ONCOL, V24, P51Ferrandina G, 2002, J CLIN ONCOL, V20, P973Peters WA, 2000, J CLIN ONCOL, V18, P1606Therasse P, 2000, J NATL CANCER I, V92, P205Keys HM, 1999, NEW ENGL J MED, V340, P1154Sardi JE, 1997, GYNECOL ONCOL, V67, P61Leborgne F, 1997, INT J RADIAT ONCOL, V37, P343NAMKOONG SE, 1995, GYNECOL ONCOL, V59, P136KIM DS, 1989, GYNECOL ONCOL, V33, P225SARDI JE, 1986, GYNECOL ONCOL, V25, P139

Generation of a Dystrophin Mutant in Dog by Nuclear Transfer Using CRISPR/Cas9-Mediated Somatic Cells: A Preliminary Study

© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Dystrophinopathy is caused by mutations in the dystrophin gene, which lead to progressive muscle degeneration, necrosis, and finally, death. Recently, golden retrievers have been suggested as a useful animal model for studying human dystrophinopathy, but the model has limitations due to difficulty in maintaining the genetic background using conventional breeding. In this study, we suc-cessfully generated a dystrophin mutant dog using the CRISPR/Cas9 system and somatic cell nuclear transfer. The dystrophin mutant dog displayed phenotypes such as elevated serum creatine kinase, dystrophin deficiency, skeletal muscle defects, an abnormal electrocardiogram, and avoidance of am-bulation. These results indicate that donor cells with CRISPR/Cas9 for a specific gene combined with the somatic cell nuclear transfer technique can efficiently produce a dystrophin mutant dog, which will help in the successful development of gene therapy drugs for dogs and humans.11Nsciescopu

Survival impact of extended cycles of second-line chemotherapy in platinum-sensitive relapsed ovarian cancer patients with residual tumor after six cycles

Background To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy. Methods In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups. Results The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84–1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72–2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery. Conclusions More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy