Advancements in nanomedicine: Precision delivery strategies for male pelvic malignancies - Spotlight on prostate and colorectal cancer.

BACKGROUND: Pelvic malignancies consistently pose significant global health challenges, adversely affecting the well-being of the male population. It is anticipated that clinicians will continue to confront these cancers in their practice. Nanomedicine offers promising strategies that revolutionize the treatment of male pelvic malignancies by providing precise delivery methods that aim to improve the efficacy of therapeutic outcomes while minimizing side effects. Nanoparticles are designed to encapsulate therapeutic agents and selectively target cancer cells. They can also be loaded with theragnostic agents, enabling multifunctional capabilities. OBJECTIVE: This review aims to summarize the latest nanomedicine research into clinical applications, focusing on nanotechnology-based treatment strategies for male pelvic malignancies, encompassing chemotherapy, radiotherapy, immunotherapy, and other cutting-edge therapies. The review is structured to assist physicians, particularly those with limited knowledge of biochemistry and bioengineering, in comprehending the functionalities and applications of nanomaterials. METHODS: Multiple databases, including PubMed, the National Library of Medicine, and Embase, were utilized to locate and review recently published articles on advancements in nano-drug delivery for prostate and colorectal cancers. CONCLUSION: Nanomedicine possesses considerable potential in improving therapeutic outcomes and reducing adverse effects for male pelvic malignancies. Through precision delivery methods, this emerging field presents innovative treatment modalities to address these challenging diseases. Nevertheless, the majority of current studies are in the preclinical phase, with a lack of sufficient evidence to fully understand the precise mechanisms of action, absence of comprehensive pharmacotoxicity profiles, and uncertainty surrounding long-term consequences.

Chemotherapy regimen for recurrent uterine leiomyosarcoma.

INTRODUCTION: Uterine leiomyosarcoma is a rare gynecological malignancy, the limited literature indicated that doxorubicin alone or gemcitabine/docetaxel combination is the preferred chemotherapy regimen. Given the rarity of the disease and the lack of high-level clinical evidence, there is no consensus on the best treatment. CASE REPORT: We report a case of a patient with uterine leiomyosarcoma who recurred after adjustment treatment with doxorubicin, gemcitabine, docetaxel, and anlotinib; and required a new chemotherapy regimen. MANAGEMENT AND OUTCOMES: The follow-up chemotherapy regimen was doxorubicin-liposome 40 mg/m2 on one day in combination with dacarbazine 250 mg/m2 on one to five days of intravenous infusion every 21 days. We monitored adverse effects during chemotherapy and the process was smooth. DISCUSSION: It is important to comprehensively consider the patient's condition, and fully consider the efficacy, dosage, and adverse reactions of the chemotherapy regimen to determine the appropriate plan, in order to achieve the best therapeutic benefits for patients.

A case of pelvic giant cell tumor of bone, complete remission with denosumab: long duration of response.

Although giant cell tumor of bone has been considered as a disease with benign course, it can lead to bone destruction and serious morbidity. A 19-year-old case was presented with hip pain. There was a recurrence after 9 months of curative surgical resection and zoledronic acid use, and as surgical morbidity would be high, antiosteoclastic receptor activator of nuclear factor kappa B ligand inhibitor denosumab treatment was administered. She had a complete remission after 18 months of denosumab treatment. The important point in the present case is that it has been followed up without recurrence after around 42 months of denosumab use and 11 months of follow-up after the cessation of drug. In recurrent cases in which nonmetastatic surgery is not suitable, the use of denosumab decreases tumor progression. The duration of use in unresectable and advanced cases still remains unclear.

The efficacy of the ganglion impar block in perineal and pelvic cancer pain.

BACKGROUND: Visceral pain conducted by sympathetic fibers with pelvic and perineal origin can be treated using ganglion impar (GIB) or Walters' block in a simple and effective manner. This article aims to evaluate the effectiveness, security, and performance difficulty of GIB in patients with pelvic and perineal oncological pain. METHODS: A retrospective study between January 2016 and August 2017. Patients with poorly controlled pelvic oncological pain and patients experimenting opioid side effects in which GIB was performed ambulatory were included. Prognostic GIB was performed, under echographic and fluoroscopic control, with local anesthetic and corticoid. The neurolytic block was performed under fluoroscopic guidance. The technique was performed by the same anesthetist with pain management competence. For statistical analysis, Microsoft Excel 2013® and IBM SPSS Statistics version 22.0 were used. RESULTS: Fifteen patients were included. One patient was excluded. A statistical significant basal pain score reduction was observed ((median of the verbal numerical scale (VNS) 7 (p25 = 7; p75 = 8)) compared with 72 h median VNS 4 ((p25 = 3; p75 = 5.3) p = 0.001, and 3 months (median VNS 4 (p25 = 3, p75 = 7)) p = 0.003 after the procedure. Regarding morphine consumption, a statistically significant reduction was observed 3 months after GIB performance (p = 0.012). DISCUSSION/CONCLUSION: GIB is a safe and easy-to-perform technique achieving satisfactory and statistically significant results, regarding pain control improvement and opioid consumption reduction in patients which meet selection criteria. Prospective, randomized studies with more patients are needed for further conclusions.

Efficacy of bevacizumab and temozolomide therapy in locally advanced, recurrent, and metastatic malignant solitary fibrous tumour: A population-based analysis.

BACKGROUND: Patients with locally advanced, recurrent or metastatic solitary fibrous tumour are often treated with bevacizumab and temozolomide based on the clinical efficacy reported in a case series of 14 patients. Given the rarity of solitary fibrous tumour, large trials are not feasible. We report the efficacy of this regimen based on a population-based analysis. METHODS: This was a population-based retrospective, multi-centre analysis using patient data from a provincial cancer registry and treatment database. Cases from June 2006 through October 2016 were identified for patients receiving bevacizumab and temozolomide for locally advanced, recurrent or metastatic solitary fibrous tumour or hemangiopericytoma, which is sometimes used to describe tumours arising from the meninges. The primary outcome was overall response rate. Secondary outcomes included time to response, progression free survival and overall survival estimated using the Kaplan-Meier method. RESULTS: Fourteen patients were identified: median age 59 (range 44-70), male 78.6%. Diagnoses were solitary fibrous tumour in 10 (71.4%) and hemangiopericytoma in four (28.6%), with metastatic disease in 10 (72.7%) patients. The most common primary sites were meninges in four (28.6%) and pelvis in three (21.4%) patients. The median follow-up was 15.5 months, with median treatment of four months. Overall response rate was 21.4% (no complete response, 3 partial response), with median time to response of four months. Median progression free survival, six-month progression free survival and overall survival were 17 months, 65.0%, and 45 months, respectively. CONCLUSIONS: Efficacy of bevacizumab and temozolomide in solitary fibrous tumour appeared to be similar to that previously reported. Our findings confirmed that bevacizumab and temozolomide is an effective and tolerated treatment for this patient population.

Huge abdominal and perineal aggressive angiomyxoma: A misdiagnosed case report and literature review.

Aggressive angiomyxoma (AA) is a distinctive soft tissue tumor with a high risk of local recurrence. Clinicians must be aware of this rare tumor pre-operatively. Excision is the preferred method of AA treatment. The case report presents a case of a 36-year-old woman who was difficulty in walking due to a non-painful tumor in the abdomen and perineum. She was misdiagnosed as abdomen neurofibroma for more than 10 years, and an operation was performed in 1997. However, the tumor was incompletely resected because its huge volume accompanies with extensive infiltration and bleeding. The tumors in her abdomen and perineum were growing gradually, and the latter became a large lump which impeded her daily life. In 2008, the perineal tumor was incompletely resected, which weighed 10725 g. The severe hemorrhage had been ceased by Gonadotropin-Releasing Hormone treatment. She is alive till now. Details of the history and operative procedures are presented. An AA diagnosis was made by microscopy immunohistochemically. Long-time misdiagnosis and improper treatment are the important reasons for making it impossible to be radically resected. Pathological and immunohistochemical examination are important for avoiding misdiagnosis. For this case, there is a remaining tumor in her abdomen. A special project including further follow-up and treatment will be taken out.

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

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

Does Locoregional Chemotherapy Still Matter in the Treatment of Advanced Pelvic Melanoma?

Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision. Among the 41 patients, 22 (53.7%) patients exhibited a wild-type BRAF genotype, 11 of which were not eligible for immunotherapy. The first treatment resulted in a 97.5% response-rate in the full cohort and a 100% response-rate in the 22 wild-type BRAF patients. MST was 18 months in the full sample, 20 months for the 22 wild-type BRAF patients and 21 months for the 11 wild-type BRAF patients not eligible for immunotherapy. Melphalan hypoxic perfusion is a potentially effective treatment for patients with pelvic melanoma loco regional metastases that requires confirmation in a larger multicenter study.

Diffusion-weighted MR imaging of metastatic abdominal and pelvic tumours is sensitive to early changes induced by a VEGF inhibitor using alternative diffusion attenuation models.

OBJECTIVES: To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor. MATERIALS AND METHODS: Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed. RESULTS: Diffusion coefficient repeatabilities from all models were < 6%; f and D* (bi-exponential) were 22% and 44%; α (stretched-exponential) was 4.2%. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed. CONCLUSION: DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes. KEY POINTS: • Non-mono-exponential diffusion models widen sensitivity to a broader class of tissue properties. • A stretched-exponential model robustly detects changes after 7 days of VEGF-inhibitor treatment. • There are very weak correlations between DWI-IVIM perfusion and similar DCE-MRI measures. • Diffusion-weighted MRI is a highly informative technique for assessing novel tumour therapies.

Neoadjuvant Intraarterial Chemotherapy for Treatment of Malignant Vaginal Tumors in Children: A Single-Center Experience.

Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.

Surgical treatment of recurrent urachal carcinoma with liver metastasis: a case report and literature review.

BACKGROUND: Urachal carcinoma is a rare malignancy with poor prognosis due to late presentation of the disease and its aggressiveness. Surgery remains the mainstay of therapy even in cases of disease recurrence. To the best of our knowledge, this is the first report of salvage surgery in the case of urachal carcinoma with liver metastasis. CASE PRESENTATION: The patient was a young woman who suffered from locally advanced urachal carcinoma treated with en-bloc cystectomy, hysterectomy with bilateral adnexectomy, partial resection of the sigmoid colon, and partial resection of the rectus abdominis muscle with the fascia, skin, and umbilicus. Adjuvant chemotherapy with paclitaxel and carboplatin was applied. Two years after the treatment, she was diagnosed with a single liver metastasis and a local pelvic recurrence. In a two-step operation, the patient underwent right hemihepatectomy as well as resection of pelvic recurrence site and adjuvant chemotherapy with gemcitabine. Due to the disease progression, a complete resection of the lesions was not achieved and the response to chemotherapy was poor. The patient died of the disease after a year. CONCLUSIONS: Surgery is the first line of treatment for urachal carcinoma and should be always considered as an option in cases of disease recurrence. Radical initial surgical management, close patient surveillance, and prompt treatment of disease relapse may all contribute to prolonging patient's survival.

Evaluation of chemotherapeutic sequelae and quality of life in survivors of malignant sacrococcygeal teratoma.

PURPOSE: The impact of chemotherapeutic sequelae on long-term quality of life (QoL) for survivors of malignant sacrococcygeal teratoma (SCT) is unknown. The incidence of chemotherapeutic toxicity in patients treated for malignant SCT and possible effects on the QoL were analyzed. METHODS: Retrospective chart review of patients ≥18 years treated for SCT in the Netherlands was performed. Present QoL was evaluated using the SF-36 questionnaire. The results of survivors of malignant SCT were compared to those of patients treated for benign SCT. RESULTS: Fifty-one of 76 traceable patients consented to participate. The results of 47 (92.2 %), 9 men and 38 women (median age 25.4 years, range 18.3-41.2), were analyzed. Eleven had been treated for malignancy; 63.6 % suffered from at least one chemotherapeutic sequel with hearing loss as the most common one. Results for both groups were similar on all but one SF-36 subcategory; those treated for malignant tumor scored significantly lower on the subcategory physical functioning (p = 0.02). CONCLUSION: Despite the high incidence of chemotherapeutic sequelae among survivors of malignant SCT, their QoL does not differ from that of those treated for benign SCT. Even though their physical functioning is restricted, daily activities and psychosocial functioning of survivors of malignant SCT are not restricted.

Isolated pelvic perfusion in treatment for malignant tumors.

Rationale and feasibility of isolated pelvic perfusion (IPP) as a high-tech treatment modality for patients with pelvic malignancies was studied and analyzed based on the systematic review of the literature. Indications, techniques and regimens of IPP are reviewed. There is a focus on anticancer agents for IPP and methods of complete vascular isolation of the perfusated region. Data on the short- and long-term outcome of patients after IPP are presented. To the best of authors' knowledge this is the first Russian article regarding application of IPP in oncology practice.

OLIGOPELVIS - GETUG P07: a multicentre phase II trial of combined salvage radiotherapy and hormone therapy in oligometastatic pelvic node relapses of prostate cancer.

BACKGROUND: Metastatic prostate cancer remains a common cause of death in Europe, and improvements in management of the disease are urgently needed. The advent of positron-emission tomography (PET) imaging enhanced with fluorocholine has led to the identification of a new sub-group of metastatic prostate cancer patients: those with so-called oligometastatic disease. Presenting with a low burden of metastatic disease (≤5 lesions), this new sub-group lies between true metastatic prostate cancer patients for whom androgen- deprivation therapy (ADT) is the mainstay of treatment, and patients with a rising PSA, but no visible lesion on conventional imaging, in whom intermittent ADT has been shown to be no less effective than continuous ADT. One might conclude that intermittent ADT would also be the standard of care for oligometastatic prostate cancer patients, but radical strategies such as extensive lymphadenectomy or high-dose radiotherapy have been suggested as another means to delay the need for ADT, and increase its effectiveness once initiated. This study will explore the role of salvage pelvic image-guided intensity-modulated radiation therapy (IMRT) combined with ADT administered for 6 months in pelvic oligometastatic patients in prolonging the failure-free interval between two consecutive ADT courses, or even to cure selected patients with limited metastatic burden. METHODS/DESIGN: We plan to assess the two year outcome in oligometastatic prostate cancer patients (1-5 pelvic oligometastases) treated concomitantly with high-dose IMRT (54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) and ADT for six months. DISCUSSION: This multicenter prospective phase II study will yield new data regarding the safety and efficacy of high-dose radiotherapy combined with ADT and will provide a basis for a larger phase III study to examine the role of radiotherapy in this population currently treated only with hormone therapy. TRIAL REGISTRATION: NCT02274779 , date of registration: 23/10/14.

Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit.

OBJECTIVES: To evaluate the use of post-discharge venous thromboembolism (VTE) prophylaxis in UK pelvic cancer centres consistent with national guidelines. METHODS: Data was collected from healthcare professionals from 64 UK pelvic cancer centres. RESULTS: After radical cystectomy (RC), all cancer centres routinely use low-molecular-weight heparin (LMWH) in the perioperative period. After RC 67% of cancer centres use post-discharge LMWH routinely. After radical prostatectomy (RP), 98% of units use perioperative LMWH VTE prophylaxis routinely. After RP, 61% of hospitals always use post-discharge LMWH. In all, 27% of all UK cancer centres reported deaths or serious VTE complications from urological pelvic cancer surgery in the last 2 years. CONCLUSIONS: The National Institute for Health and Care Excellence (NICE) issued explicit guidance of VTE prophylaxis after pelvic and abdominal cancer surgery. Conversion of national guidance into local policy is ≈60% for UK pelvic cancer centres. A lack of good quality evidence is cited as a reason for not adhering to NICE guidance.

Extraintestinal gastrointestinal stromal tumor of undetermined origin: Is the mass resection a wrong approach? A case report and review of the literature.

Gastrointestinal stromal tumor (GIST) was first defined by Mazur et al. in 1983. GIST is evaluated among tumoral lesions that can be acquired or congenital. Those not associated with gastrointestinal system are termed as extragastrointestinal stromal tumor (EGIST). EGISTs can develop on intraperitoneal spaces as omentum, mesenterium and gallbladder and they can occur on retroperitoneum, extraperitoneal (prostate) and intrapelvic organs. Herein, we present a case with EGIST in a 65-year-old male patient located in intrapelvic and retroprostatic area which had no connection with gastrointestinal system as assessed by radiological methods and we discuss its treatment. We reviewed the literature and observed that ours is the first case report on a patient in which the mass was only extirpated rather than performing radical surgery. He is still at the 2. year of his follow-up period without any disease recurrence.

[A CASE OF HEPATIC METASTASECTOMY FOR RENAL PELVIS CARCINOMA].

A 68-year-old woman presented with asymptomatic gross hematuria. Computed tomography (CT) scan revealed noninvasive tumor in the right ureteropelvic junction. After diagnosis with right pelvis carcinoma by ureteroscopy, she underwent laparoscopic nephroureterectomy in Aug. 2008. Six months later, hepatic metastasis was detected. Three courses of combination chemotherapy consisting of gemcitabine and cisplatin (GC) were conducted, and then partial response (PR) was achieved. In Aug. 2009, radical metastasectomy for liver metastasis was performed. More than four years and five months after hepatectomy, the patient has achieved a high quality of life.

Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on pretreatment imaging.

BACKGROUND: The significance of lateral pelvic lymph node (LPLN) metastasis in advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) remains unclear. The objective of this study was to evaluate the outcomes of selective LPLN dissection (LPLD) based on the pretreatment imaging in patients with advanced low rectal cancer treated with preoperative CRT. METHODS: We reviewed 127 consecutive patients with clinical stage II-III low rectal cancer below the peritoneal reflection who underwent preoperative CRT and curative resection. LPLD was performed in patients with suspected LPLN metastasis based on MDCT or MRI before CRT (LPLD group, N = 38), and only total mesorectal excision (TME) was performed in patients without suspected LPLN metastasis (TME group, N = 89). Clinical characteristics and the oncological outcome were compared between groups. RESULTS: The median tumor-to-anal verge distance was 40 mm in both groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3 patients (3.4 %) in the TME group and in none (0 %) of the LPLD group. Multivariate analysis showed that only ypN was an independent prognostic factor for relapse-free survival (RFS), but LPLN metastasis was not associated with poor RFS. CONCLUSIONS: The incidence of LPLN metastasis is high even after preoperative CRT, and LPLD might improve local control and survival of patients with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.

Hormonal therapy for aggressive angiomyxoma: a case report and proposed management algorithm.

OBJECTIVE: This study aimed to report the results of hormonal therapy in the management of a patient with recurrent aggressive angiomyxoma (AAM) and to propose a management strategy for AAM based on (1) the estrogen receptor (ER) and progestin receptor contents of the tumor (2) the extent of disease based on magnetic resonance imaging findings and (3) the patient's menopausal status. MATERIALS AND METHODS: The chart of a patient with multiple pelvic recurrences of AAM managed surgically during a 16-year period followed by hormonal therapy was reviewed, and a literature search of pelvic, vaginal, and vulva AAM was performed. RESULTS: The patient presented in this report experienced 7 recurrences of AAM managed surgically during a 16-year period. She then was placed on leuprolide acetate for 3 monthly cycles, but the tumor recurred 6 months after the leuprolide acetate was discontinued. The patient was placed back on monthly leuprolide acetate for 5 years and has remained free of disease for more than 2 years after discontinuing the leuprolide acetate. A literature review suggest a role for hormonal therapy in the management of AAM based on the presence of ER/progestin receptor, the extent of the disease, and the menopausal status of the patient. Gonadotropin-releasing hormone analogs have been successfully used in premenopausal women as neoadjuvant therapy before surgery for previously untreated or recurrent disease, as adjuvant therapy after the initial surgical resection or after the resection of recurrent disease, and as the definitive treatment of AAM. Aromatase inhibitors may play a role in the treatment of ER-positive AAM occurring in postmenopausal women. CONCLUSIONS: Aggressive angiomyxoma can be an extremely hormonally sensitive tumor. Hormonal therapy may have a significant role in the treatment of patients with extensive or recurrent AAM that is ER positive. The selection of hormonal agents used for treating AAM can be based on the patient's menopausal status.

[Docetaxel for small cell carcinoma of the prostate with a metastatic pelvic tumor: a case report].

Small cell carcinoma of the prostate is known to have a poor prognosis. We report a case of a large pelvic tumor with small cell carcinoma, which responded well to docetaxel. A 72-year-old man who was receiving androgen-deprivation therapy for prostatic adenocarcinoma presented with constipation. Although the prostate specific antigen level had decreased, a large pelvic tumor was detected between the prostate and the rectum, which caused bowel obstruction. A biopsy of the pelvic tumor revealed small cell carcinoma of the prostate, and chemotherapy with docetaxel and prednisolone was administered. Five months after the administration of docetaxel, the pelvic tumor disappeared completely. At the time of the last follow up, the response was still maintained.