Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Trends in the Use of Opioids vs Nonpharmacologic Treatments in Adults With Pain, 2011-2019.

Importance: Chronic pain prevalence among US adults increased between 2010 and 2019. Yet little is known about trends in the use of prescription opioids and nonpharmacologic alternatives in treating pain. Objectives: To compare annual trends in the use of prescription opioids, nonpharmacologic alternatives, both treatments, and neither treatment; compare estimates for the annual use of acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy; and estimate the association between calendar year and pain treatment based on the severity of pain interference. Design, Setting, and Participants: A serial cross-sectional analysis was conducted using the nationally representative Medical Expenditure Panel Survey to estimate the use of outpatient services by cancer-free adults with chronic or surgical pain between calendar years 2011 and 2019. Data analysis was performed from December 29, 2021, to August 5, 2022. Exposures: Calendar year (2011-2019) was the primary exposure. Main Outcomes and Measures: The association between calendar year and mutually exclusive pain treatments (opioid vs nonpharmacologic vs both vs neither treatment) was examined. A secondary outcome was the prevalence of nonpharmacologic treatments (acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy). All analyses were stratified by pain type. Results: Among the unweighted 46 420 respondents, 9643 (20.4% weighted) received surgery and 36 777 (79.6% weighted) did not. Weighted percentages indicated that 41.7% of the respondents were aged 45 to 64 years and 55.0% were women. There were significant trends in the use of pain treatments after adjusting for demographic factors, socioeconomic status, health conditions, and pain severity. For example, exclusive use of nonpharmacologic treatments increased in 2019 for both cohorts (chronic pain: adjusted odds ratio [aOR], 2.72; 95% CI, 2.30-3.21; surgical pain: aOR, 1.53; 95% CI, 1.13-2.08) compared with 2011. The use of neither treatment decreased in 2019 for both cohorts (chronic pain: aOR, 0.43; 95% CI, 0.37-0.49; surgical pain: aOR, 0.59; 95% CI, 0.46-0.75) compared with 2011. Among nonpharmacologic treatments, chiropractors and physical therapists were the most common licensed healthcare professionals. Conclusions and Relevance: Among cancer-free adults with pain, the annual prevalence of nonpharmacologic pain treatments increased and the prevalent use of neither opioids nor nonpharmacologic therapy decreased for both chronic and surgical pain cohorts. These findings suggest that, although access to outpatient nonpharmacologic treatments is increasing, more severe pain interference may inhibit this access.

GALNT14 genotype-guided chemoembolization plus sorafenib therapy in hepatocellular carcinoma: a randomized trial.

BACKGROUND: GALNT14-rs9679162 "TT" genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 "non-TT" unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy. METHODS: Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with "TT" genotype received only TACE, labeled as TT (TACE) group. Patients with "non-TT" genotype ("GG" or "GT") were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE. RESULTS: From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p < 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p < 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, < 0.001, respectively). CONCLUSION: Combination of sorafenib and TACE for "non-TT" patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT02504983.

Treatment strategy of adding transcatheter arterial chemoembolization to sorafenib for advanced stage hepatocellular carcinoma.

BACKGROUND: Therapeutic effect and immunosuppressor cell alteration in adding transcatheter arterial chemoembolization (TACE) to sorafenib for advanced stage hepatocellular carcinoma (HCC) remain unclear. AIMS: To examine the therapeutic effect and immunosuppressor cell alteration in adding TACE to sorafenib. METHODS: Forty-four advanced stage HCC patients were divided into group A (n = 17) treated by sorafenib (400-600 mg/day) alone and group B patients (n = 27) treated by sorafenib and TACE. The frequency of regulatory T-cells and myeloid-derived suppressor cells (MDSC), and patients' outcomes were examined. Advanced HCC patients' survival was improved by adding TACE to sorafenib if N/L was reduced from ≥2.5 to <2.5 by TACE. RESULTS: The median (interquartile) follow-up for all patients was 8.5 (3.5 to 15.5) with a range from 1 to 71 months. The median (interquartile) survival was 5.0 (2.3-11.3) months for group A and 11.0 (5.0-19.0) months for group B patients (P = .024). In group A, the patients (n = 8) with neutrophil-to-lymphocytes ratio (N/L) < 2.5 had better survival than the patients (n = 9) with N/L ≥ 2.5 (P = .006). In group B, 6 of 13 patients with N/L ≥ 2.5 had N/L reduction to <2.5 after combination therapy of sorafenib and TACE, and their 6-month, 1-year and 2-year survival were improved (P = .013). For immune cell examination, the frequency of CD4+ and CD8+ T-lymphocytes, regulatory T-cell and MDSC were not altered by sorafenib treatment. However, actual number of lymphocytes had a tendency to increase (from 978.5 ± 319.4/mm3 prior to treatment to 1378.0 ± 403.3/mm3 , P = .086) for the patients with N/L reduction. CONCLUSION: Immunosuppressor cells were not altered by sorafeinb. Patients' survival was improved if N/L ≥ 2.5 was reduced to <2.5 by TACE.

A novel thyroid function index associated with opposite therapeutic outcomes in advanced hepatocellular carcinoma patients receiving chemotherapy or sorafenib.

AIM: A sustained proportion of advanced hepatocellular carcinoma (HCC) patients worldwide received either chemotherapy or sorafenib. However, to date, effective and convenient biomarkers to predict their therapeutic outcomes remained elusive. Hypothyroidism was associated with favorable anticancer treatment outcomes in several advanced cancers. Here, we aimed to investigate the potential of using thyroid-stimulating hormone (TSH) and free T4 (FT4) levels as biomarkers to predict clinical outcomes in HCC patients receiving chemotherapy or sorafenib. METHODS: Total 123 advanced HCC patients at Barcelona Clinical Liver Cancer Stage C were included. They were separated into two cohorts, one treated by sorafenib (n = 62) and the other by chemotherapy (n = 61). Clinical data including TSH and FT4 were retrieved and correlated with treatment outcomes. RESULTS: Because of restriction in local insurance policy, the baseline liver function reserve was better in patients receiving sorafenib. Therefore, the two cohorts were analyzed separately. The results showed that a higher (> median) TSH × FT4 value was independently associated with favorable time-to-tumor progression (P = 0.006) and overall survival (P = 0.002) if chemotherapy was provided; whereas it was associated with unfavorable time-to-tumor progression (P = 0.017) and overall survival (P = 0.001) if sorafenib was administrated. These opposite associations remained valid when patients with Child-Pugh class A liver function from either cohort were included for analysis. CONCLUSION: A novel thyroid function index, TSH × FT4, significantly predicted opposite clinical outcomes in advanced HCC patients receiving sorafenib or chemotherapy treatment.

Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.

BACKGROUND: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. METHODS: All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis. RESULTS: Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage. CONCLUSION: Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.

Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment.

BACKGROUND AND PURPOSE: The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment. METHODS: We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined. RESULTS: Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p < 0.0001). CONCLUSION: The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.