Tenofovir-Induced Fanconi Syndrome Presenting with Life-Threatening Hypokalemia: Review of the Literature and Recommendations for Early Detection.

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor that has been widely used for the treatment of patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. However, in the HBV monoinfection scenario, only five cases of TDF-associated Fanconi syndrome have been reported thus far, two of them providing a confirmatory kidney biopsy. Here, we describe the case of a 68-year-old woman with chronic hepatitis B (CHB) who developed TDF-induced Fanconi syndrome that reverted after TDF withdrawal from tenofovir alafenamide. Though the overall risk of TDF-associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular functions should be monitored in patients exposed to TDF.

The Impact of Trophoblast Cell-Surface Antigen 2 Expression on the Survival of Patients with Gastrointestinal Tumors: A Systematic Review.

BACKGROUND: Trophoblast cell-surface antigen 2 (TROP-2) is a transmembrane glycoprotein expressed in epithelial cells that has been associated with malignant progression in most carcinomas. Accordingly, the genetic complexity of gastrointestinal tumors necessitates the investigation of new biomarkers with potential prognostic value. The aim of this systematic review is to assess the effect of TROP-2 on the overall survival of patients who underwent surgery for gastrointestinal malignancy. METHODS: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched the Pubmed, EMBASE and CENTRAL databases from their inception to September 2023. RESULTS: Ten studies that enrolled 2293 patients were included for qualitative analysis. Six studies evaluated patients with colorectal cancer, two studies included patients with gastric carcinoma, patients with pancreatic cancer were included in one study and one study included hepatobiliary cancer patients. TROP-2 was positive in 1005/2293 samples of the immunohistochemically evaluated biopsies and was associated with poor overall survival in all studies. High intensity was also associated with more aggressive histopathological characteristics, such us deep tissue invasion, lymph node metastasis and cell atypia. The prognostic value of TROP-2 was shown to be enhanced in patients with advanced disease and poor histological differentiation. CONCLUSION: TROP-2 was expressed at high levels in gastrointestinal tumors, which was associated with both tumor development and pathological aggressiveness. Therefore, TROP-2 could be used as a biomarker to determine clinical prognosis and as a potential therapeutic target in malignancies of the gastrointestinal tract, but further studies need to validate it.

Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis.

The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33-0.50) for hematological malignancies and 0.56 (95%CI: 0.47-0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57-0.67) for hematological malignancies and 0.88 (95%CI: 0.82-0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54-0.72) for hematological cancer and 0.88 (95%CI: 0.75-0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process.

Current status and novel insights into the role of metastasectomy in the era of immunotherapy.

INTRODUCTION: New perspectives on the role of metastasectomy have emerged along with the advances in cancer immunotherapy. Despite accumulating evidence that encourages the use of immunotherapy in the metastatic setting, current data regarding its combination with surgical resection of secondary lesions, as well as the best timeline and sequence of such a therapeutic approach is limited. AREAS COVERED: We review the currently available literature on the role of metastasectomy in the era of novel immunotherapeutic agents and provide comprehensive evidence from ongoing trials about the available treatment strategies. In metastatic melanoma, immune checkpoint inhibitors (ICIs) play a key role both in the neoadjuvant and adjuvant setting to achieve long-term disease control. In metastatic renal cell carcinoma, investigation is ongoing regarding the emerging role of ICIs before metastasectomy. ICIs have improved outcomes in patients with metastatic colorectal and head and neck cancer. EXPERT OPINION: In the neoadjuvant setting, the high response rates and the durability of responses to immunotherapy may enable the resectability of metastatic lesions. In the adjuvant setting post metastasectomy, immunotherapy constitutes a safe and efficacious approach to support immune tumor surveillance and delay or even prevent disease relapse. Patient participation in relevant clinical trials should be encouraged.

The impact of surgery delay on survival of resectable pancreatic cancer: A systematic review of observational studies.

BACKGROUND: Pancreatic cancer is considered a lethal disease and the only potentially curative option is R0 excision. The aim of this study was to investigate whether the waiting time interval from diagnosis to surgical treatment affects overall survival in patients who undergo curative-intent surgery for pancreatic cancer. METHODS: Search in Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases was conducted from inception until April 2022. RESULTS: Overall, 10 studies were included that enrolled 181,344 patients. The dominating cut-off time point was 4 weeks in studies which utilized a biphasic waiting time pattern. In addition, prolonged waiting time interval was associated with decreased overall survival in 3 studies, whereas it demonstrated a favorable effect on overall survival in 2 studies and no impact on survival in 5 studies. CONCLUSION: The great diversity that was observed regarding the impact of surgery delay on survival underlines the lack of knowledge about biologic pathways of pancreatic cancer. Novel imaging studies and molecular "fingerprints" in combination to time-to-treatment standardization in the design of future randomized trials could lead to the recognition of patients that could benefit from a timely resection.

Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis.

The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.

Perineural Invasion as a Predictive Biomarker of Groin Metastases and Survival Outcomes in Vulvar Cancer: A Meta-Analysis.

We searched international databases to identify evidence that refer to the impact of perineural invasion on survival outcomes of patients with squamous cell vulvar cancer. We identified six retrospective cohort studies that investigated 887 patients. Of those, 234 (26.4%) had perineural invasion in the pathology analysis. Women with perineural invasion were more likely to have inguinal lymph node metastases (HR 3.45, 95% CI 1.12, 10.67). The impact of perineural invasion on progression-free survival rates was significant (HR 1.61, 95% CI 1.21, 2.15) as well as its impact on overall survival rates (HR 2.73, 95% CI 1.94, 3.84).

Quality of life of ovarian cancer patients treated with combined platinum taxane chemotherapy: a systematic review of the literature.

PURPOSE: Chemotherapy is the cornerstone of adjuvant therapy in ovarian cancer. Its impact on the quality of life (QoL) has been addressed in several studies; however, several misperceptions concerning this affect patient counseling and physicians' ability to overcome patient fears. In the present systematic review, we sought to accumulate current evidence in the field in order to help establish robust information that will help physicians answer patients' questions. METHODS: The present systematic review is based on the PRISMA guidelines. Studies that evaluated patient QoL pre-, during, and post-chemotherapy with the use of the QLQC-30 were selected for inclusion. Their methodological quality was assessed with the before-after studies tool that is proposed by the National Institute of Health (NIH). RESULTS: Ten studies that involved 5181 patients were included in the present systematic review. The risk of bias and methodological quality of included studies was of good and fair overall quality. Retrieved data suggest there is substantial evidence that points toward improved global QoL among ovarian cancer patients treated with taxanes-platinum combination therapy. Individual outcomes evaluated with the QLQ-C30 also provide positive results, although underreporting was noted. CONCLUSION: Despite the significant heterogeneity in outcome reporting, the findings of this study reveal the significant benefit of combined platinum taxane chemotherapy on the QoL of ovarian cancer patients and can be used for patients counseling in order to reduce refusals that arise from fear of adverse effects that may negatively affect QoL. Graphical abstract.

Presentation and surgical management of xanthogranulomatous cholecystitis.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. DATA SOURCES: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases from inception until June 2020. RESULTS: The laparoscopic cholecystectomy rate (34%) was almost equal to the open cholecystectomy rate (47%) for XGC. An important conversion rate (35%) was observed as well. The XGC cases treated by surgery were associated with low mortality (0.3%), limited intraoperative blood loss (58-270 mL), low complication rates (2%-6%), along with extended operative time (82.6-120 minutes for laparoscopic and 59.6-240 minutes for open cholecystectomy) and hospital stay (3-9 days after laparoscopic and 8.3-18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. CONCLUSIONS: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.