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Gynecologic Oncology May 2023Uterine leiomyosarcomas (uLMS) are rare, highly aggressive tumors. Up to 30% of uLMS may harbor gain of function (GOF) in the MAP2K4 gene, important for tumor cell...
INTRODUCTION
Uterine leiomyosarcomas (uLMS) are rare, highly aggressive tumors. Up to 30% of uLMS may harbor gain of function (GOF) in the MAP2K4 gene, important for tumor cell proliferation, differentiation and metastasis. We investigated the in vivo activity of a novel MAP2K4 inhibitor, PLX8725, against uLMS harboring MAP2K4 gene-amplification.
METHODS
Two fully characterized uLMS (i.e., LEY-11 and LEY-16) were grafted into female CB-17/SCID mice. Treatments with control vehicle or PLX8725 (50 mg/kg) were given via oral gavage daily on weekdays for up to 60 days. Tumor volume differences were calculated with two-way ANOVA. Pharmacokinetic (PK) and mechanistic studies of PLX8725 in uLMS PDX models were also performed.
RESULTS
Both uLMS tumors evaluated demonstrated GOF in MAP2K4 (i.e., 3 CNV in both LEY-11 and LEY-16). Tumor growth inhibition was significantly greater in both PDX LEY-11 and PDX LEY-16 treated with PLX8725 when compared to controls (p < 0.001). Median overall survival was also significantly longer in both PDX LEY-11 (p = 0.0047) and PDX LEY-16 (p = 0.0058) treatment cohorts when compared to controls. PLX8725 oral treatment was well tolerated, and PK studies demonstrated that oral PLX8725 gives extended exposure in mice. Ex vivo tumor samples after PLX8725 exposure decreased phosphorylated-ATR, JNK and p38, and increased expression of apoptotic molecules on western blot.
CONCLUSION
PLX8725 demonstrates promising in vivo activity against PDX models of uLMS harboring GOF alterations in the MAP2K4 gene with tolerable toxicity. Phase I trials of PLX8725 in advanced, recurrent, chemotherapy-resistant uLMS patients are warranted.
Topics: Humans; Female; Animals; Mice; Leiomyosarcoma; Gene Amplification; Mice, SCID; Neoplasm Recurrence, Local; Uterine Neoplasms; Pelvic Neoplasms; MAP Kinase Kinase 4
PubMed: 36958197
DOI: 10.1016/j.ygyno.2023.03.009 -
Role of pelvic and para-aortic lymphadenectomy in abandoned radical hysterectomy in cervical cancer.World Journal of Surgical Oncology Jan 2017Cervical cancer (CC) occupies fourth place in cancer incidence and mortality worldwide in women, with 560,505 new cases and 284,923 deaths per year. Approximately, nine...
BACKGROUND
Cervical cancer (CC) occupies fourth place in cancer incidence and mortality worldwide in women, with 560,505 new cases and 284,923 deaths per year. Approximately, nine of every ten (87%) take place in developing countries. When a macroscopic nodal involvement is discovered during a radical hysterectomy (RH), there is controversy in the literature between resect macroscopic lymph node compromise or abandonment of the surgery and sending the patient for standard chemo-radiotherapy treatment. The objective of this study is to compare the prognosis of patients with CC whom RH was abandoned and bilateral pelvic lymphadenectomy and para-aortic lymphadenectomy was performed with that of patients who were only biopsied or with removal of a suspicious lymph node, treated with concomitant radiotherapy/chemotherapy in the standard manner.
METHODS
A descriptive and retrospective study was conducted in two institutions from Mexico and Colombia. Clinical records of patients with early-stage CC programmed for RH with an intraoperative finding of pelvic lymph, para-aortic nodes, or any extracervical involvement that contraindicates the continuation of surgery were obtained. Between January 2007 and December 2012, 42 clinical patients complied with study inclusion criteria and were selected for analysis.
RESULTS
In patients with CC whom RH was abandoned due to lymph node affectation, there is no difference in overall survival or in disease-free period between systematic lymphadenectomy and tumor removal or lymph node biopsy, in pelvic lymph nodes as well as in para-aortic lymph nodes, when these patients receive adjuvant treatment with concomitant radiotherapy/chemotherapy.
CONCLUSIONS
This is a hypothesis-generator study; thus, the recommendation is made to conduct randomized prospective studies to procure better knowledge on the impact of bilateral pelvic and para-aortic lymphadenectomy on this group of patients.
Topics: Adenocarcinoma; Adult; Aorta; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Hysterectomy; Immunoenzyme Techniques; Lymph Node Excision; Middle Aged; Neoplasm Grading; Neoplasm Staging; Pelvic Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Uterine Cervical Neoplasms
PubMed: 28088221
DOI: 10.1186/s12957-016-1067-2 -
The British Journal of Radiology May 2019To evaluate outcomes and toxicity profiles after re-irradiation in patients with pelvic recurrence of anorectal cancer.
OBJECTIVE
To evaluate outcomes and toxicity profiles after re-irradiation in patients with pelvic recurrence of anorectal cancer.
METHODS
25 anorectal cancer patients who received re-irradiation for pelvic recurrence between 2005 and 2015 were included. For initial treatment, all patients underwent surgical resection and preoperative or postoperative radiotherapy.
RESULTS
The median follow-up duration was 21.5 months (range, 2.9-84.4). After a median of 43.3 months (range, 11.7-218.5), patients received re-irradiation with a median dose of 45 Gy (range, 36-60). The equivalent dose in 2 Gy fractions (EQD2) of re-irradiation-calculated using α/β = 10 Gy-ranged from 34.5 to 84.0 Gy (median, 46.4). Surgical resection was performed for 11 patients, and 14 patients received concurrent chemotherapy with re-irradiation. The 3-year local progression-free survival was 29.7%. The 3-year overall survival was 49.7%. Concurrent chemotherapy with re-irradiation and re-irradiation doses >50 Gy EQD2 were significant prognostic factors for local progression free survival and overall survival according to multivariate analysis. 90% (9 of 10) of patients with symptoms had improvement after re-irradiation. Among 23 patients available for evaluation of late toxicity, 12 developed late toxicities. There were no Grade 4 late toxicities, and 6 patients had Grade 3 late toxicities (small bowel obstruction, bowel perforation and fistula).
CONCLUSION
Re-irradiation for pelvic recurrence of anorectal cancer improved symptoms of patients but the rate of late toxicity was high. Further investigation for patient selection is required.
ADVANCES IN KNOWLEDGE
Re-irradiation could be considered as a possible option for pelvic recurrence of anorectal cancer in selected patients.
Topics: Adenocarcinoma; Adult; Aged; Anus Neoplasms; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pelvic Neoplasms; Progression-Free Survival; Radiotherapy Dosage; Radiotherapy, Adjuvant; Re-Irradiation; Rectal Neoplasms; Survival Analysis
PubMed: 30864822
DOI: 10.1259/bjr.20180794 -
Scientific Reports Mar 2021While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG...
While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.
Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Multimodal Imaging; Pelvic Neoplasms; Penile Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Tumor Burden
PubMed: 33723317
DOI: 10.1038/s41598-021-85300-8 -
Archives of Gynecology and Obstetrics Mar 2023Uterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection...
PURPOSE
Uterine sarcoma (US) as a histologically heterogeneous group of tumors is rare and associated with poor prognosis. Prognostic factors based on systematic data collection need to be identified to optimize patients' treatment.
METHODS
This unicenter, retrospective cohort study includes 57 patients treated at the University Hospital Freiburg, Germany between 1999 and 2017. Progression-free survival (PFS) and overall survival (OS) were calculated and visualized in Kaplan-Meier curves. Prognostic factors were identified using log-rank test and Cox regression.
RESULTS
44 Leiomyosarcoma (LMS), 7 low-grade endometrial stromal sarcoma (LG-ESS), 4 high-grade ESS and 2 undifferentiated US patients were identified. The median age at time of diagnosis was 51.0 years (range 18-83). The median follow-up time was 35 months. PFS for the total cohort was 14.0 (95%-Confidence-Interval (CI) 9.7-18.3) and OS 36.0 months (95%-CI 22.1-49.9). Tumor pathology was prognostically significant for OS with LG-ESS being the most favorable (mean OS 150.3 months). In the multivariate analysis, patients over 52 years showed a four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-CI 1.5-12.9). Progesterone receptor negativity was associated with a two times higher risk for death (HR 2.8; 95%-CI 1.0-7.5). For LMS patients age ≥ 52 years (p = 0.04), clear surgical margins (p = 0.01), FIGO stage (p = 0.01) and no application of chemotherapy (p = 0.02) were statistically significant factors for OS.
CONCLUSION
Tumor histology, age at time of diagnosis and progesterone receptor status were prognostic factors for US. Unfavorable OS in LMS patients was associated with advanced FIGO stage, suboptimal cytoreduction and application of chemotherapy.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Prognosis; Retrospective Studies; Receptors, Progesterone; Neoplasm Recurrence, Local; Sarcoma; Uterine Neoplasms; Leiomyosarcoma; Endometrial Stromal Tumors; Pelvic Neoplasms; Sarcoma, Endometrial Stromal; Endometrial Neoplasms; Survival Rate
PubMed: 35780401
DOI: 10.1007/s00404-022-06515-2 -
The British Journal of Radiology 2016Our objective is to describe an approach for retrorectal/presacral mass evaluation on imaging with attention to imaging features, allowing for refinement of the... (Review)
Review
Our objective is to describe an approach for retrorectal/presacral mass evaluation on imaging with attention to imaging features, allowing for refinement of the differential diagnosis of these masses. Elaborate on clinically relevant features that may affect biopsy or surgical approach, of which the radiologist should be aware. A review of current literature regarding the diagnosis and treatment of retrorectal/presacral masses was performed with attention to specific findings, which may lend refinement to the differential diagnosis of these masses. Cases were obtained by searching through a radiology database at a single institution after Institutional Review Board approval. Recent advances in imaging and treatment methods have led to the increased role of radiology in both imaging and tissue diagnosis of retrorectal masses. Surgical philosophies surrounding the treatment of these masses have not significantly changed in recent years, but there are a few key factors of which the radiologist must be aware. The radiologist can offer refinement of the differential diagnosis of retrorectal masses and can elaborate on salient findings which could alter the need for neoadjuvant chemoradiation therapy, pre-surgical tissue diagnosis and surgical approach. This article presents an imaging approach to retrorectal/presacral masses with emphasis on findings which can dictate the ultimate need for neoadjuvant therapy and pre-surgical tissue diagnosis and alter the preferred surgical approach. This article consolidates key findings, so radiologists can become more clinically relevant in the evaluation of these masses.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Pelvic Neoplasms; Sacrococcygeal Region; Tomography, X-Ray Computed
PubMed: 26828969
DOI: 10.1259/bjr.20150698 -
International Journal of Gynecological... May 2021Triaging patients with presumptive ovarian cancer to the appropriate specialist may improve survival. Therefore, there is increasing interest in complementary diagnostic... (Observational Study)
Observational Study
OBJECTIVE
Triaging patients with presumptive ovarian cancer to the appropriate specialist may improve survival. Therefore, there is increasing interest in complementary diagnostic markers to the standard serum CA125. In patients with pelvic masses, we examined the ability of epidemiologic variables and preoperative differential blood counts to improve detection of ovarian cancer over CA125 alone.
METHODS
From pathology reports, patients were classified as having: epithelial ovarian cancer (n=743), including fallopian tube and primary peritoneal cancer, non-epithelial ovarian cancers (n=46), non-ovarian cancers (n=122), or benign disease (1,129). From women with epithelial ovarian cancer, we excluded those who received prior neoadjuvant chemotherapy (n=19). Women were also excluded if they did not have a serum CA125 or complete blood count measured within 180 days prior to surgery (n=1099) or did not have both tests within 90 days of each other (n=13). Categorizing patients by menopausal status, we calculated Pearson correlations between differential counts or ratios and CA125, and used t tests to identity univariate predictors of malignancy and stepwise logistic regression and likelihood ratio tests to create models best distinguishing epithelial ovarian cancer from benign disease.
RESULTS
337 women with epithelial ovarian cancer and 365 with benign disease were included in the analysis. Compared with cancers, women with benign disease had lower average: age, 52.5 versus 58.4 years (p<0.0001); serum CA125, 20 versus 239 U/mL (p<0.0001), neutrophil-to-lymphocyte ratio, 2.4 versus 3.5 (p<0.0001); and platelet-to-lymphocyte ratio, 158 versus 222 (p<0.0001); but greater average body mass index, 28.5 versus 26.8 kg/m (p=0.004), and lymphocyte-to-monocyte ratio, 5.6 versus 3.9 (p<0.0001). Correlations between counts and ratios and serum CA125 were seen in both epithelial ovarian cancer and benign disease groups and differed by menopausal status. In premenopausal women, a multivariate model including serum CA125, smoking, family history, lymphocytes, and monocytes performed similarly to the model with lymphocyte-to-monocyte ratio replacing counts. In postmenopausal women, a model including body mass index, parity, monocytes, and basophils performed similarly to the model replacing counts with platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio. Models including epidemiologic variables and either counts or ratios were better at fitting data than models with serum CA125 and menopausal status alone. A single model applying to all women overstated performance for premenopausal women and understated performance for postmenopausal women.
CONCLUSIONS
Epidemiologic variables and differential counts or ratios better distinguished between benign and malignant disease when compared with serum CA125 alone using separate models for pre- and postmenopausal women.
Topics: Aged; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Diagnosis, Differential; Female; Humans; Membrane Proteins; Middle Aged; Ovarian Neoplasms; Pelvic Neoplasms; Prospective Studies
PubMed: 32487682
DOI: 10.1136/ijgc-2019-001103 -
Asian Journal of Surgery Sep 2017In locally advanced pelvic malignancies, there is often involvement of urological organs, necessitating resection and reconstruction, which can be associated with...
BACKGROUND
In locally advanced pelvic malignancies, there is often involvement of urological organs, necessitating resection and reconstruction, which can be associated with significant complications.
METHODS
We retrospectively reviewed 20 patients undergoing urological reconstructions during pelvic oncological surgeries from January 2004 to December 2013. All patients had imaging-proven involvement of at least one urological organ preoperatively. Primary outcome was urological complication rate. Secondary outcomes were nonurological complication, recurrence rate, and overall survival.
RESULTS
Median age of presentation was 51 years. Six and 14 patients underwent resections for primary and secondary tumors, respectively. Colorectal tumors were the most common, followed by gynecological cancers. The ureter was the most common urological organ involved, followed by the bladder, prostate, and seminal vesicles. Reconstructive procedures included ileal and sigmoid conduits, ureteroneocystostomies, Boari flap, transureteroureterostomies (TUUs) and direct ureteroureterostomies. Six patients developed major urological complications, requiring endoscopic and surgical reinterventions. The follow-up time was 34 months. Thirteen patients developed recurrence, associated with higher tumor grade and lymphovascular invasion, and occurred at a median time of 10 months. These patients had an overall survival of 20 months, compared to 45 months in patients without recurrence.
CONCLUSION
Careful patient selection in pelvic oncological surgeries can significantly prolong survival. Recurrent tumors and greater intraoperative blood loss are associated with higher urological complications. A limited pelvic exenteration and lower radiation doses can reduce complication rates. If higher doses are necessary, conformal techniques and hyperfractionated radiotherapy should be explored. Urological reconstruction should be individualized, according to the extensiveness of urological involvement and exposure of radiation.
Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pelvic Exenteration; Pelvic Neoplasms; Postoperative Complications; Plastic Surgery Procedures; Retrospective Studies; Survival Rate; Urologic Neoplasms; Urologic Surgical Procedures
PubMed: 27317102
DOI: 10.1016/j.asjsur.2016.02.002 -
The British Journal of Radiology Jul 2020To evaluate the imaging characteristics of aggressive angiomyxoma (AA) and identify features which would help to differentiate it from similar appearing lesions. (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate the imaging characteristics of aggressive angiomyxoma (AA) and identify features which would help to differentiate it from similar appearing lesions.
METHODS
A retrospective review of departmental records was done and cases where AA was suspected on CT or MRI were included. With histopathology as gold-standard, the cases were grouped into AA or mimics and differentiating features were identified on USG, CT and MRI. Fischer's exact test was applied for the statistical significance of the differentiating features.
RESULTS
18 patients were identified of which 2 were excluded for lack of histopathology records. 10 were AA and 6 mimics which included 2 fibromatoses, 2 neurogenic tumors, and 1 each of germ cell tumor and inflammatory myofibroblastic tumor. On MRI, all AA showed T2 hyperintensity and intense contrast enhancement with characteristic laminated pattern in 7/9 cases. Diffusion restriction was seen in 2/3 cases, cystic component in 4/10 and hemorrhage in 1/10 cases. Pelvic fibromatosis was the closest imaging differential showing laminated pattern in one of the cases.
CONCLUSION
Large pelvic mass with abdominal/perineal extension in reproductive age female patient should lead to suspicion of AA. Laminated pattern on weighted images and intense homogeneous contrast enhancement further add to the diagnostic confidence.
ADVANCES IN KNOWLEDGE
This study for the first time describes radiological mimics of AA. Large cystic component, diffusion restriction, hemorrhage and organ infiltration have not been previously described in AA.
Topics: Abdominal Neoplasms; Adolescent; Adult; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Multidetector Computed Tomography; Myxoma; Pelvic Neoplasms; Perineum; Retrospective Studies; Young Adult
PubMed: 32401545
DOI: 10.1259/bjr.20200255 -
Ghana Medical Journal Dec 2022To review the Computed Tomography( CT )features of pediatric oncological patients with abdominal and pelvic tumours and correlate these findings with their...
OBJECTIVES
To review the Computed Tomography( CT )features of pediatric oncological patients with abdominal and pelvic tumours and correlate these findings with their histopathological diagnosis.
DESIGN
This was a retrospective cross-sectional facility-based study.
SETTING
This study was conducted in the Pediatric Oncology Unit and Radiology Department of the Korle Bu Teaching Hospital.
PARTICIPANTS
Fifty-six pediatric oncology patients with contrast-enhanced abdominal and pelvic CT scans.
DATA COLLECTION
The abdominal and pelvic CT scans findings, patient biodata, and histopathology reports of oncology patients over four years were reviewed.
STATISTICAL ANALYSIS
Simple descriptive statistics using frequency distribution, percentages, means, and standard deviation were used to describe the various variables and presented tables.
RESULTS
The four commonest tumours were nephroblastoma, neuroblastoma, lymphoma, and hepatoblastoma. The mean age at diagnosis was 4.8 years, with a slightly higher male predominance. The majority of the tumours were extremely large at presentation. Overall, the CT - histopathology concordance was 79.2%.
CONCLUSION
Abdominal and pelvic CT scans play an important role in the diagnostic workup of pediatric malignancies by ensuring early and accurate diagnosis of these tumours.
FUNDING
None declared.
Topics: Child; Humans; Male; Child, Preschool; Female; Ghana; Pelvic Neoplasms; Retrospective Studies; Cross-Sectional Studies; Hospitals, Teaching; Tomography, X-Ray Computed; Tomography
PubMed: 37575625
DOI: 10.4314/gmj.v56i4.8