Advances in nanotechnology-enabled drug delivery for combining PARP inhibitors and immunotherapy in advanced ovarian cancer.

Advanced ovarian cancer is a malignancy that spreads beyond the ovaries to the pelvis, abdomen, lungs, or lymph nodes. Effective treatment options are available to improve survival rates in patients with advanced ovarian cancer. These include radiation, surgery, chemotherapy, immunotherapy, and targeted therapy. Drug resistance, however, remains a significant challenge in pharmacotherapeutic interventions, leading to reduced efficacy and unfavorable patient outcomes. Combination therapy, which involves using multiple drugs with different mechanisms of action at their optimal dose, is a promising approach to circumvent this challenge and it involves using multiple drugs with different mechanisms of action at their optimal dose. In recent years, nanotechnology has emerged as a valuable alternative for enhancing drug delivery precision and minimize toxicity. Nanoparticles can deliver drugs to specific cancer cells, resulting in higher drug concentrations at the tumor site, and reducing overall drug toxicity. Nanotechnology-based drug delivery systems have the potential to improve the therapeutic effects of anti-cancer drugs, reduce drug resistance, and improve outcomes for patients with advanced ovarian cancer. This literature review aims to examine the current understanding of combining poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy in treating advanced ovarian cancer and the potential impact of nanotechnology on drug delivery.

Fusion-negative rhabdomyosarcoma with diffuse bony metastases and remarkable chemosensitivity.

In this report, we describe the case of an adolescent male with an unusual case of fusion-negative, paratesticular alveolar rhabdomyosarcoma who presented with spontaneous tumour lysis syndrome and diffuse bony metastases throughout the axial and appendicular skeleton with additional significant bone marrow involvement. Both spontaneous tumour lysis syndrome and diffuse bony metastases are extremely unusual for rhabdomyosarcoma. On the backbone of standard vincristine, dactinomycin and cyclophosphamide (VAC) chemotherapy, the only local control was orchiectomy at 15 weeks, with no radiation administered due to the initially diffuse nature of the disease and rapid response to chemotherapy. Following 43 weeks of VAC, a year-long maintenance phase with pazopanib was given which was well tolerated. The patient remains in remission now 4 years after completion of therapy.

Successful treatment of a case of hormone receptor-positive metastatic extramammary Paget disease with tamoxifen.

Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma that usually is of epidermal origin and shows glandular differentiation and that is treated by wide local excision depending on the disease extent. For widely metastatic disease, however, a standard treatment remains to be established. Similar to breast cancer, EMPD has been found to overexpress human epidermal growth factor receptor 2 (HER2) or hormone receptors (HRs). Whereas HER2-directed therapy was recently shown to be effective for HER2-positive EMPD, the potential role of endocrine therapy for HR-positive EMPD has remained unknown. We here report a case of metastatic EMPD with HR positivity that was successfully treated with the selective estrogen receptor modulator tamoxifen. This first-line treatment of systemic metastasis resulted in durable tumor regression for > 20 months without any treatment-related toxicities. This is the first report to reveal the promise of tamoxifen as a safe and effective treatment for HR-positive metastatic EMPD.

Complete clearance of condyloma acuminata using injection Vitamin D3.

Anogenital warts (AGWs) are caused by human papilloma virus (HPV) and are transmitted by sexual route. The available options for the treatment of AGWs are cumbersome, require multiple sittings and are associated with recurrence. This is a case report of a male with condyloma acuminata who was treated successfully using injection vitamin D3. No recurrence was observed in a follow-up period of 6 months.

Curcumin: a phytochemical modulator of estrogens and androgens in tumors of the reproductive system.

Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.

A case of eribulin-induced regression of liposarcoma of the left funiculus in a heavily pretreated patient.

We report the case of a heavily pretreated male subject affected by left funiculus liposarcoma and successfully treated with eribulin mesylate. After three surgical interventions, radiotherapy on the lesion of the penile bulb for satellite nodules and an epirubicin + ifosfamide chemotherapy treatment for six cycles, eribulin was administered at the dose of 1.1 mg/m2 on days 1 and 8, every 3 weeks for a total of nine cycles. A significant reduction of the lesions was achieved after four cycles of therapy, with a good profile of tolerability.

Primary scrotal melanoma: it is time to destigmatize genital lesions.

Primary male genital melanomas are very rare; they are associated with high mortality and late detection. Scrotal melanoma is the least common presentation and only 23 cases have been reported. Herein, the authors present a 30-year-old patient with stage IIIC (T4b, N2a, M0) scrotal melanoma in order to report the characteristics, treatment, and outcome, as well as to emphasize the importance of examination of the genitals, education of patients about self-examination and destigmatizing genital lesions to increase the likelihood of earlier detection.

Primary scrotal melanoma: it is time to destigmatize genital lesions

Abstract Primary male genital melanomas are very rare; they are associated with high mortality and late detection. Scrotal melanoma is the least common presentation and only 23 cases have been reported. Herein, the authors present a 30-year-old patient with stage IIIC (T4b, N2a, M0) scrotal melanoma in order to report the characteristics, treatment, and outcome, as well as to emphasize the importance of examination of the genitals, education of patients about self-examination and destigmatizing genital lesions to increase the likelihood of earlier detection.

Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that clinicopathologically resembles breast cancer. The prognosis of metastatic EMPD is poor. Although several chemotherapies have been tried, the effects are temporary; better drugs and combinations are required.In the present study, we retrospectively analyze the efficacy and safety of combination of cisplatin, epirubicin, and paclitaxel in five metastatic EMPD cases. The efficacy was better than that for previously reported regimens: 80% partial responses, including two patients who were refractory to taxane- and/or platinum-based regimens. In terms of safety, four patients who were able to continue treatment exhibited acceptable tolerability.This is the first regimen to combine taxane and anthracycline. When treating breast cancer, anthracycline is regarded as the key cytotoxic agent, and anthracycline in combination with taxane constitutes a key chemotherapeutic regimen. Given our results, we speculate both drugs are critical chemotherapeutic agents for the treatment of metastatic EMPD.

Extramammary Paget's disease of the scrotum with complete response to imiquimod and photodynamic therapy.

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm with an extremely variable clinical course. The objective of this study was to determine if combination imiquimod and photodynamic therapy could induce remission of EMPD. A 69-year-old man with EMPD was treated with topical imiquimod 5% cream at night for 5 days per week for 1 month, followed by 2 months of 5% imiquimod for three nights a week. For the following 6 months, monthly 5-aminolevulinic acid photodynamic therapy was added. After 6 months, imiquimod was discontinued and the patient continued to be treated with quarterly photodynamic therapy. Treatment resulted in significant improvement in the appearance of the lesion, and pathology revealed no evidence of residual disease. The patient has had no clinical signs of disease for >5 years. We conclude that topical imiquimod 5% cream and photodynamic therapy may aid in the treatment of some patients with EMPD.

Therapeutic startegies for human papillomavirus infection and associated cancers.

Human papillomavirus (HPV) infection is linked to development of cancer of cervix, vagina, vulva, penis, ano-genital and non-genital oro-pharyngeal sites. HPV being a sexually transmitted virus infects both genders equally but with higher chances of pathological outcome in women. In the absence of organized screening programs, women report HPV-infected lesions at relatively advanced stages where they are subjected to standard treatments that are not HPV-specific. HPV infection-driven lesions usually take 10-20 years for malignant progression and are preceded by well-characterized pre-cancer stages. Despite availability of window for pharmacological intervention, therapeutic that could eradicate HPV from infected lesions is currently lacking. A variety of experimental approaches have been made to address this lacuna and there has been significant progress in a number of lead molecules which are in different stages of clinical and pre-clinical development. Present review provides a brief overview of the magnitude of the problem and current status of research on promising lead molecules, formulations and therapeutic strategies that showed potential to translate to clinically-viable HPV therapeutics to counteract this reproductive health challenge.

Metastatic primary seminal vesicle adenocarcinoma: management of a rare tumour with multiagent chemotherapy and hormonal therapy.

Primary seminal vesicle adenocarcinoma is one of the rarest genitourinary cancers. The pathogenesis is unknown and clinical manifestations are protean. There is no defined treatment for this disease and various combinations of surgery, chemotherapy, radiation therapy and hormonal therapy have been used in the past. Here, we have reported a primary seminal vesicle adenocarcinoma with hepatic metastases, managed with multiagent chemotherapy (oxaliplatin and 5-fluorouracil based) and androgen ablation (with triptorelin). The key to management of such a case is early diagnosis and multimodal treatment. The reported survival rate continues to be poor even for a localised disease. A consolidated follow-up protocol ensures early diagnosis of recurrent or metastatic disease so that second-line therapy can be started.

Modified weekly regimen of cisplatin, epirubicin and paclitaxel induced a durable response in two cases of metastatic extramammary Paget's disease.

Metastatic extramammary Paget's disease (EMPD) is a rare cancer with no standardized treatment. We report two cases of metastatic EMPD treated with a modified weekly PET (cisplatin, epirubicin and paclitaxel) regimen given biweekly (i.e. 2 weeks on/2 weeks off) that had durable responses. Case 1 was a 74-year-old man with EMPD metastatic to lymph nodes, lung, and bone who presented with a hemorrhagic tumor on the scrotum. We tried the PET regimen weekly, but adjusted the interval to biweekly after two doses because of hematological side-effects. After five doses, he showed a partial response (PR) on imaging, including the bone lesions. The lesions have remained the same size for 1 year. Case 2 was a 65-year-old man with EMPD metastatic to a right inguinal lymph node who presented with an erosive tumor on the scrotum. He was started on weekly docetaxel. However, the lymph node grew and iliac lymph node metastasis developed. Therefore, we tried the PET regimen with a 2 weeks on/2 weeks off schedule. After five doses, he showed a PR. In both cases, all adverse effects were manageable and this modified regimen could be administrated on an outpatient basis. With no current validated chemotherapy regimen, clinicians may consider a modified weekly PET regimen in future treatment of metastatic EMPD.

Risk-Stratified Initial Salvage Therapy for Relapsed or Refractory Metastatic Germ Cell Tumors.

BACKGROUND: Salvage treatment with either conventional-dose chemotherapy (CDCT) or high-dose chemotherapy with autologous stem cell transplantation (HDCT) offers curative potential for patients with relapsed or refractory germ cell tumor (GCT). However, the optimal initial salvage strategy remains controversial, and the criteria for appropriate patient selection are not clear. METHODS: This was a retrospective analysis of the clinical outcomes for GCT patients receiving initial salvage therapy using a risk-stratified treatment approach. In general, patients with favorable-risk disease received CDCT with 4 cycles of paclitaxel, ifosfamide, and cisplatin, while patients with unfavorable-risk disease received HDCT per institutional protocol. The prognostic validity of the International Germ Cell Cancer Collaborative Group (IGCCCG) and the International Prognostic Factors Study Group (IPFSG) risk groups were evaluated in this context. RESULTS: Thirty-seven patients received initial salvage therapy. Twenty-four patients (65%) achieved a favorable response (including complete response to chemotherapy alone, complete response after post-chemotherapy surgical resection, or partial response with negative tumor markers). The favorable response rates for the CDCT and HDCT treatment groups were 69% and 62%, respectively. After a median follow-up of 31 months, the median survival for CDCT-treated patients has not been reached, and the median survival for the HDCT-treated group was 24 months. Both the International Germ Cell Cancer Collaborative Group and the International Prognostic Factors Study Group risk groups were significantly associated with progression-free survival (log-rank P = .009 and P = .039, respectively). CONCLUSIONS: Patients with favorable prognostic features may achieve durable remissions without requiring high-dose salvage chemotherapy. However, the criteria for optimal patient selection remain unclear, and these findings further support the need for a definitive randomized trial.

Propranolol for Treatment of Genital Infantile Hemangioma.

PURPOSE: Genital infantile hemangiomas are vascular anomalies that often require complex management and interdisciplinary care. Propranolol was first used to treat patients with infantile hemangiomas in 2008 and has since gained acceptance as first-line therapy. MATERIALS AND METHODS: We review the presentation, course, management and outcomes of all cases of genital infantile hemangiomas managed by propranolol administration at a single institution from April 2010 to July 2014. RESULTS: During the study period 9 patients with genital infantile hemangiomas were referred to our hemangioma treatment clinic. Propranolol was initially administered under careful outpatient monitoring at a dose of 1 mg/kg daily in 8 patients. One patient, a 700 gm premature infant, was started on therapy in the inpatient setting at 0.5 mg/kg daily, given the history of prematurity. All patients underwent successful increase of dose to at least 2 mg/kg for the observation phase after tolerating the starting doses. One patient discontinued propranolol prematurely per parental request due to concern regarding peripheral vasoconstriction. Otherwise, no patient demonstrated significant hypotension, symptomatic bradycardia, hypoglycemia or other major side effect requiring treatment discontinuation. All patients who continued the treatment protocol had excellent response to therapy. CONCLUSIONS: Propranolol therapy for genital infantile hemangiomas was successfully initiated and the dosage increased in 9 young children without significant side effects and with marked improvement in all patients who continued on treatment. Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas.

Epitheloid hemangioma treated with naproxen sodium.

UNLABELLED: Epitheloid hemangioma (EH) is a vascular tumor characterized by an epithelioid endothelial cell. Predominantly affecting the head and neck, fewer than 30 cases involving the scrotum have been published. As this represents an extremely rare entity, a multitude of anecdotal treatment modalities have been utilized including systemic/intralesional steroid therapy, radiotherapy, and chemical therapy. However, surgical excision remains the most widely accepted treatment option.We present a case of EH of the scrotum in a 14-year-old male patient that regressed after treatment with naproxen sodium. To the best of our knowledge, this represents the first reported case of scrotal EH regression following treatment with naproxen sodium. LEVEL OF EVIDENCE: V.

Complete remission of two patients with recurrent and wide spread extramammary Paget disease obtained from 5-aminolevulinic acid-based photodynamic therapy and imiquimod combination treatment.

BACKGROUND: Extramammary Paget disease (EMPD) is an uncommon malignant neoplasm affecting apocrine gland-bearing skin which usually occurs in the anogenital area of patients older than 50 years. However, as EMPD in old men develops in penoscrotal area and sometimes asymptomatic, in situ or dermal invasion is usually widely spread before a confirmed diagnosis was made. Skin graft is needed after surgery. Both photodynamic therapy (PDT) and topical use of imiquimod reported effective for EMPD. METHODS: Two patients with recurrent and wide spread at penoscrotal and groin area were diagnosed EMPD by biopsy and histopathological and immunohistochemical examination. We use 6 cycles of 20% 5-aminolevulinic acid (ALA) photodynamic therapy guided by 5-ALA induced porphyrin fluorescence. After PDT, patients were treated by topical use of imiquimod to prevent the recurrence. RESULTS: After 6 cycles of PDT and imiquimod treatments, the patients' examination showed total remission. At the end of the 6 and 12 months, biopsy and pathology examination remain no signal of recurrence. No clinical recurrence after 24 and 36 months' follow up. CONCLUSION: The combination treatment with 20% PDT and imiquimod acquired complete remission in treatment for recurrent and wide spread extramammary Paget disease in two patients.