Shedding Light on Chemoresistance: The Perspective of Photodynamic Therapy in Cancer Management.

The persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies. This review explores the principles of PDT and discusses the concept of photodynamic priming (PDP), which augments the effectiveness of treatments like chemotherapy. Furthermore, the integration of nanotechnology for precise drug delivery at the right time and location and PDT optimization are examined. Ultimately, this study highlights the potential and limitations of PDT and PDP in cancer treatment paradigms, offering insights into future clinical applications.

Impact of histamine-2 antagonist shortage on the incidence of hypersensitivity reactions to paclitaxel: a reconsideration of premedication protocols in France (PACLIREACT Study).

PURPOSE: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. METHODS: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. RESULTS: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). CONCLUSION: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A.

PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer.

BACKGROUND: Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need. METHODS: This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated. DISCUSSION: To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease. TRIAL REGISTRATION: This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204 .

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

BACKGROUND: The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS: Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS: A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS: Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation.

We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.

Major breakthroughs in lung cancer adjuvant treatment: Looking beyond the horizon.

We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.

An Open Question: Is Non-Ionizing Radiation a Tool for Controlling Apoptosis-Induced Proliferation?

Non-ionizing radiation is commonly used in the clinical setting, despite its known ability to trigger oxidative stress and apoptosis, which can lead to damage and cell death. Although induction of cell death is typically considered harmful, apoptosis can also be beneficial in the right context. For example, cell death can serve as the signal for new tissue growth, such as in apoptosis-induced proliferation. Recent data has shown that exposure to non-ionizing radiation (such as weak static magnetic fields, weak radiofrequency magnetic fields, and weak electromagnetic fields) is able to modulate proliferation, both in cell culture and in living organisms (for example during tissue regeneration). This occurs via in vivo changes in the levels of reactive oxygen species (ROS), which are canonical activators of apoptosis. This review will describe the literature that highlights the tantalizing possibility that non-ionizing radiation could be used to manipulate apoptosis-induced proliferation to either promote growth (for regenerative medicine) or inhibit it (for cancer therapies). However, as uncontrolled growth can lead to tumorigenesis, much more research into this exciting and developing area is needed in order to realize its promise.

A systematic review of phase II trials exploring anti-PD-1/PD-L1 combinations in patients with solid tumors.

BACKGROUND: A high number of combinations of PD-1/PD-L1 inhibitors with other anti-cancer therapies are in clinical development. The usefulness of phase II trials in evaluating their efficacy and safety is unclear. MATERIALS AND METHODS: We performed a systematic search on PubMed and Cochrane Library for phase II trials of PD-1/PD-L1 inhibitors in combination with other anti-cancer therapies (systemic therapy and/or radiotherapy) published between January 1st 2018 and December 31st 2020. Study design, primary endpoint and main outcomes were registered for each paper. RESULTS: 119 articles reporting on 65 regimens were included in our analysis. Backbone agents were more frequently PD-1 inhibitors (pembrolizumab = 47, nivolumab = 41, camrelizumab = 3) followed by anti-PD-L1 (durvalumab = 19, atezolizumab = 6, avelumab = 3). Therapeutic partners were other immunotherapeutic agents (n = 46), targeted therapies (n = 40), chemotherapy (n = 22) or radiotherapy (n = 11). The majority of articles reported on single-arm trials (n = 87, 73%) and response rate was the most frequent primary endpoint (n = 69, 58%). Objective responses, registered in 109 (92%) articles, ranged between 0% and 91%. The incidence of grade 3 or higher treatment-related adverse events, clearly reported in 97 (82%) articles, spanned from 0 to 100%. Five combinations received regulatory approval by Food and Drug Administration or European Medicine Agency for 9 different indications, based on the results of a phase II trial (n = 3) or on a confirmatory phase III trial (n = 6). CONCLUSIONS: The landscape of phase II trials evaluating PD-1/PD-L1 inhibitors with other anticancer therapies is heterogeneous. Combinations of two immunotherapeutic agents have been the most investigated. Only a minority of indications (8%) granted regulatory approval.

De-escalation of axillary irradiation for early breast cancer - Has the time come?

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

In-vitro and in-vivo investigation of amygdalin, metformin, and combination of both against doxorubicin on hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is a potentially life-threatening cancer. In the current study, anti-HCC efficacy of amygdalin, or metformin alone or in combination in comparison to doxorubicin was studied. MAIN METHODS: Both in-vitro and in-vivo based models. HepG-2 and Huh-7 cell lines as established in-vitro model for HCC were treated with different concentrations of indicated drugs to evaluate the cytotoxicity and determine IC50 for 24, 48 and 72 h. Moreover, the effect of different treatments on apoptosis and cell cycle using flow cytometric analysis were studied. Hepatocellular carcinoma induced in rats by diethyl-nitrosamine and carbon tetrachloride was established, to further investigate the efficacy of indicated drugs. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were measured by spectrophotometer, alpha-fetoprotein, cytochrome-c, caspase-3 and malondialdehyde were measured by ELISA, and liver biopsies were also evaluated histopathologically. KEY FINDINGS: In-vitro results showed that the combination has a promising effect when compared to amygdalin or metformin alone as it is more cytotoxic and have higher ability for induction of apoptosis and arresting cell cycle. In-vivo doxorubicin has a good effect for treating HCC. Also, the combination showed a promising prognostic effect depending on the cytotoxic activity and tumor marker when compared to amygdalin or metformin alone. SIGNIFICANCE: Based on the current data, it was hypothesized that amygdalin and metformin especially when used in combination will be a promising approach with low side effects for enhancement of HCC.

Demographic Factors Associated With Non-Guideline-Based Treatment of Kidney Cancer in the United States.

Importance: Significant demographic disparities have been found to exist in the delivery of health care. Demographic factors associated with clinical decision-making in kidney cancer have not been thoroughly studied. Objective: To determine whether demographic factors, including sex and race/ethnicity, are associated with receipt of non-guideline-based treatment for kidney cancer. Design, Setting, and Participants: This retrospective cohort study was conducted using data from the National Cancer Database for the years 2010 through 2017. Included patients were individuals aged 30 to 70 years with localized (ie, cT1-2, N0, M0) kidney cancer and no major medical comorbidities (ie, Charlson-Deyo Comorbidity Index score of 0 or 1) treated at Commission on Cancer-accredited health care institutions in the United States. Data were analyzed from November 2020 through March 2021. Exposures: Demographic factors, including sex, race/ethnicity, and insurance status. Main Outcomes and Measures: Receipt of non-guideline-based treatment (undertreatment or overtreatment) for kidney cancer, as defined by accepted clinical guidelines, was determined. Results: Among 158 445 patients treated for localized kidney cancer, 99 563 (62.8%) were men, 120 001 individuals (75.7%) were White, and 91 218 individuals (57.6%) had private insurance. The median (interquartile range) age was 58 (50-64) years. Of the study population, 48 544 individuals (30.6%) received non-guideline-based treatment. Female sex was associated with lower adjusted odds of undertreatment (odds ratio [OR], 0.82; 95% CI, 0.77-0.88; P < .001) and higher adjusted odds of overtreatment (OR, 1.27; 95% CI, 1.24-1.30; P < .001) compared with male sex. Compared with White patients, Black and Hispanic patients had higher adjusted odds of undertreatment (Black patients: OR, 1.42; 95% CI, 1.29-1.55; P < .001; Hispanic patients: OR, 1.20; 95% CI, 1.06-1.36; P = .004) and overtreatment (Black patients: OR, 1.09; 95% CI, 1.05-1.13; P < .001; Hispanic patients: OR, 1.06; 95% CI, 1.01-1.11, P = .01). Individuals who were uninsured, compared with those who had insurance, had statistically significantly higher adjusted odds of undertreatment (OR, 2.63; 95% CI, 2.29-3.01; P < .001) and lower adjusted odds of overtreatment (OR, 0.72; 95% CI, 0.67-0.77; P < .001). Conclusions and Relevance: This study found that there were significant disparities in treatment decision-making for patients with kidney cancer, with increased rates of non-guideline-based treatment for women and Black and Hispanic patients. These findings suggest that further research into the mechanisms underlying these disparities is warranted and that clinical and policy decision-making should take these disparities into account.

Biology of primary breast cancer in older women beyond routine biomarkers.

PURPOSE: There are numerous biomarkers which may have potential predictive and prognostic significance in breast cancer. This is extremely important in older adults, who may opt for less aggressive therapy. This work outlines the literature on biological assessment outside of standard biomarkers (defined as ER, PgR, HER2, Ki67) in women ≥ 65 years with primary operable invasive breast cancer, to determine which additional biomarkers are relevant to outcome in older women. METHODS: Medline and Embase databases were searched. Studies were eligible if included ≥ 50 patients aged ≥ 65 years; stratified results by age; measured a biomarker outside of standard assay and reported patient data. RESULTS: A total of 12 studies were appraised involving 5000 patients, measuring 28 biomarkers. The studies were extremely varied in methodology and outcome but three themes emerged: 1. Differences in biomarker expression between younger and older women, indicating that breast cancer in older women is generally less aggressive compared to younger women; 2. Relationship of biomarker expression with survival, suggesting biomarkers which may exclusively predict response to primary treatment in older women; 3. Association of biomarker with chemotherapy, suggesting that older patients should not be declined chemotherapy based on age alone. CONCLUSION: There is evidence to support further investigation of B-cell lymphoma (BCL2), liver kinase (LK)B1, epidermal growth factor receptor (EGFR), cytoplasmic cyclin-E, mucin (MUC)1 and cytokeratins (CKs) as potential predictive or prognostic markers in older women with breast cancer undergoing surgery. Studies exploring these biomarkers in larger cohorts and in women undergoing non-operative therapies are required.

Glycosaminoglycans: Carriers and Targets for Tailored Anti-Cancer Therapy.

The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics. This review will comprehensively discuss recent developments and the broad potential of GAG utilization for cancer therapy.

The Stanley Prostate-cancer Treatment Protocol for Erectile Dysfunction After Prostatectomy and/or Radiotherapy: A Case Report.

Even when a diagnosis of prostate cancer is anticipated, many patients are unprepared for the persistence and severity of sequelae such as erectile dysfunction, which frequently results from lifesaving treatment for that disease. Erectile dysfunction in particular can exert a powerful impact on quality of life as the patient's self-esteem diminishes, intimacy erodes, and a sustained level of stress and anxiety that impairs work performance and personal relationships becomes a part of his everyday experience. The Stanley Prostate-cancer Protocol for treating erectile dysfunction after prostatectomy and/or radiotherapy was developed to better assist the underserved patient population faced with that challenge. Feedback from patients and prescribers indicates that this program, even when initiated years after treatment for prostate cancer, is consistently effective in treating erectile dysfunction. The authors have also found that incorporating the Protocol into a range of pharmacy services can further the growth of a compounding practice. In this case report, the outcome of Stanley-Protocol therapy in a patient complaining of complete and persistent erectile dysfunction after prostate-cancer treatment is presented and formulations used in therapy for that disorder are provided.

The implementation of a national paediatric oncology protocol for neuroblastoma in South Africa.

PURPOSE: The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children's Cancer Study Group. METHODS: The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process. RESULTS: The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation. CONCLUSION: The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible.

Survival analysis and treatment strategies for limb liposarcoma patients with metastasis at presentation.

ABSTRACT: Limited data exist on patients with limb liposarcoma (LLS) with metastasis at presentation Moreover, the potential prognostic factors of this patient population are poorly documented because of its rarity. Therefore, we conducted this study to evaluate the clinicopathologic characteristics and prognostic factors for patients with metastatic LLS.All patients with LLS with metastasis at presentation from 1975 to 2016 were identified by using the Surveillance, Epidemiology, and End Results (SEER) database. The following clinical data were derived from this clinical database: age, sex, histologic grade, subtype, size of tumor, surgery, radiotherapy, chemotherapy, vital status, cause of death, and survival duration. The Kaplan-Meier method was performed to calculate median survival time and draw survivorship curves. Cox-proportional hazards regression model was used to reveal the statistical independence between various variables.The present study collected 184 cases from SEER database for survival analysis. Mean age was 57.8 years with 63.6% (n = 117) men. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates of this population were 27.8% and 30.1%, respectively. Univariate analysis revealed that age, tumor grade, and surgery were significantly correlated with survival. Sex and tumor size did not reach significant predictor status of survival. Multivariate analysis revealed that age at diagnosis <60, low tumor grade, and local surgery were significantly correlated with improved OS and CSS.Patients with LLS with metastasis at diagnosis experienced quite poor prognosis. Currently, surgery for the primary tumor significantly prolonged the survival of those patients, whereas chemotherapy and radiotherapy need to be further confirmed.

Treatment stage migration and treatment sequences in patients with hepatocellular carcinoma: drawbacks and opportunities.

PURPOSE: This retrospective analysis focuses on treatment stage migration in patients with hepatocellular carcinoma (HCC) to identify successful treatment sequences in a large cohort of real-world patients. METHODS: 1369 HCC patients referred from January 1993 to January 2020 to the tertiary center of the Heidelberg University Hospital, Germany were analyzed for initial and subsequent treatment patterns, and overall survival. RESULTS: The most common initial treatment was transarterial chemoembolization (TACE, n = 455, 39.3%) followed by hepatic resection (n = 303, 26.1%) and systemic therapy (n = 200, 17.3%), whereas the most common 2nd treatment modality was liver transplantation (n = 215, 33.2%) followed by systemic therapy (n = 177, 27.3%) and TACE (n = 85, 13.1%). Kaplan-Meier analysis revealed by far the best prognosis for liver transplantation recipients (median overall survival not reached), followed by patients with hepatic resection (11.1 years). Patients receiving systemic therapy as their first treatment had the shortest median overall survival (1.7 years; P < 0.0001). When three or more treatment sequences preceded liver transplantation, patients had a significant shorter median overall survival (1st seq.: not reached; 2nd seq.: 12.4 years; 3rd seq.: 11.1 years; beyond 3 sequences: 5.5 years; P = 0.01). CONCLUSION: TACE was the most common initial intervention, whereas liver transplantation was the most frequent 2nd treatment. While liver transplantation and hepatic resection were associated with the best median overall survival, the timing of liver transplantation within the treatment sequence strongly affected median survival.

Primary diffuse large B-cell lymphoma of the fallopian tube treated with a combination of surgery and chemotherapy: Case report.

RATIONALE: Primary female genital tract lymphomas are sporadic neoplasms, accounting for 0.2% to 1.1% of all cases of extranodal lymphoma. The most common genital localizations are the cervix, the uterine corpus and the ovary, while primary lymphomas of the fallopian tube are quite unusual. According to literature searching in PubMed, this is the first reported case of primary diffuse large B-cell lymphoma of the fallopian tube. PATIENT CONCERNS: A 52-year-old woman presented with a more than 2 months history of intermittent lower abdominal pain. The gynecological examination showed that the uterus, as big as 3 months of pregnancy, had weak activity and no tenderness. The uterine rectum lacuna was like a hard nodule of about 3 × 2 cm, and an irregular solid mass was fixed and inactive in the right adnexa. DIAGNOSES: In accordance with Ann Arbor staging system, a stage IE primary diffuse large B-cell lymphoma of fallopian tube was diagnosed for this patient, based on the tumor pathology, the results of bone marrow biopsy and computed tomography (CT) scan. INTERVENTIONS: After gynecological/urinary ultrasound, blood test, pelvic contrast enhanced CT scan and CT angiography of iliac artery, exploratory laparoscopy and following hysterectomy with bilateral salpingo-oophorectomy were performed. After the surgery, the patient was treated with combined Rituximab and chemotherapy and got complete response (CR). OUTCOMES: After the operation and R-CHPOP, following up for more than 1 year so far, the patient has no tumor recurrence and is still in good condition. LESSONS: It is very difficult to diagnose the primary diffuse large B-cell lymphoma of fallopian tube, not only because of its rarity, but also because of its non-specific clinical manifestations. It easily be treated as late ovarian cancer by gynecologist. So the pathology diagnosis and surgeons' decision is very important. Because lymphoma is pretty sensitive to chemotherapy and easy to get complete response, so we no need to do an operation like ovarian cancer and should put chemotherapy as a primary method for lymphomas of the female genital tract.

Reversing Erectile Dysfunction and Urinary Incontinence After Prostatectomy or Radiotherapy: The Stanley Prostate-Cancer Treatment Protocol.

Although prostatectomy and radiotherapy yield excellent- long term survival rates for men with prostate cancer, adverse effects (erectile dysfunction and/or urinary incontinence with subsequent undesired lifestyle modifications, anxiety about the loss of intimacy, negative self-perception, and the effects of such stressors on work performance and family relationships) frequently afflict patients who have undergone these procedures. Surgeons who specialize in the treatment of prostate cancer are dedicated to ensuring the optimal clinical result but often do not provide information about the likelihood of experiencing those sequelae or the additional support and aftercare necessary to ensure posttreatment sexual and urologic function to their patients' satisfaction. In response to the needs of these underserved patients, the authors designed the Stanley Prostate-cancer Treatment Protocol for erectile dysfunction and urinary incontinence. The goal of the Stanley Protocol is to achieve an improved outcome after surgery or radiation therapy for prostate cancer via comprehensive therapy, patient monitoring, and detailed training. Each Protocol program is customized to address the individual patient's needs as he attains his desired level of sexual function and urinary control. Feedback consistently indicates that patients who participate in the Stanley Protocol achieve those goals, and the authors suggest that this program can be incorporated into any compounding practice to provide the same result. In this article, the most common questions that compounders ask about the Stanley Protocol are answered, an outline of that therapeutic guideline is presented, and formulations proven to optimize the outcome of prescribed treatment are provided.