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.

Neutrophil-to-lymphocyte-ratio-based perioperative prognosis prediction model on early mortality after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to treat peritoneal surface malignancy (PSM) has gained a positive result compared with palliative chemotherapy alone in several cancer types. However, its postoperative care could be challenging. We aimed to develop a predicting model on early mortality. METHODS: We retrospectively reviewed 132 PSM patients who had received CRS-HIPEC. The optimal cut-off value of the neutrophil-to-lymphocyte ratio (NLR) was determined as 4.4 by using the receiver operating characteristic curve analysis with an area under the curve (AUC) of 0.75. The impact of NLR on survival was elucidated by comparing the pre-operative low (NLR≤ 4.4, n = 101) and high (NLR> 4.4, n = 31) groups using the Kaplan-Meier method. The significant variables selected in multivariate analysis on early mortality were used in prediction model development. RESULTS: Multivariate analysis showed that incomplete CRS, major postoperative complications, higher pre-operative NLR, and dynamic NLR changes were significant predictors of early mortality. Our perioperative prediction of prognosis (triple P) model contained four independent risks, and the AUC after classification was 0.860 (95% confidence interval [CI]: 0.773-0.947). External validation confirmed positive discrimination ability (AUC: 0.808, 95% CI: 0.666-0.950). CONCLUSION: In conclusion, our triple P model provides great determination in outcomes prediction and it is easily obtained, reliable, and applicable in routine practice.

Optimal Perioperative Nutrition Therapy for Patients Undergoing Pancreaticoduodenectomy: A Systematic Review with a Component Network Meta-Analysis.

Numerous strategies for perioperative nutrition therapy for patients undergoing pancreaticoduodenectomy (PD) have been proposed. This systematic review aimed to summarize the current relevant published randomized controlled trials (RCTs) evaluating different nutritional interventions via a traditional network meta-analysis (NMA) and component network meta-analysis (cNMA). EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched to identify the RCTs. The evaluated nutritional interventions comprised standard postoperative enteral nutrition by feeding tube (Postop-SEN), preoperative enteral feeding (Preop-EN), postoperative immunonutrients (Postop-IM), preoperative oral immunonutrient supplement (Preop-IM), and postoperative total parenteral nutrition (TPN). The primary outcomes were general, infectious, and noninfectious complications; postoperative pancreatic fistula (POPF); and delayed gastric emptying (DGE). The secondary outcomes were mortality and length of hospital stay (LOS). The NMA and cNMA were conducted with a frequentist approach. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Two primary outcomes, infectious complications and POPF, were positively influenced by nutritional interventions. Preop-EN plus Postop-SEN (OR 0.11; 95% CI 0.02~0.72), Preop-IM (OR 0.22; 95% CI 0.08~0.62), and Preop-IM plus Postop-IM (OR 0.11; 95% CI 0.03~0.37) were all demonstrated to be associated with a decrease in infectious complications. Postop-TPN (OR 0.37; 95% CI 0.19~0.71) and Preop-IM plus Postop-IM (OR 0.21; 95% CI 0.06~0.77) were clinically beneficial for the prevention of POPF. While enteral feeding and TPN may decrease infectious complications and POPF, respectively, Preop-IM plus Postop-IM may provide the best clinical benefit for patients undergoing PD, as this approach decreases the incidence of both the aforementioned adverse effects.

Metabolism of Proteins and Amino Acids in Critical Illness: From Physiological Alterations to Relevant Clinical Practice.

The clinical impact of nutrition therapy in critically ill patients has been known for years, and relevant guidelines regarding nutrition therapy have emphasized the importance of proteins. During critical illness, such as sepsis or the state following major surgery, major trauma, or major burn injury, patients suffer from a high degree of stress/inflammation, and during this time, metabolism deviates from homeostasis. The increased degradation of endogenous proteins in response to stress hormones is among the most important events in the acute phase of critical illness. Currently published evidence suggests that adequate protein supplementation might improve the clinical outcomes of critically ill patients. The role of sufficient protein supplementation may even surpass that of caloric supplementation. In this review, we focus on relevant physiological alterations in critical illness, the effects of critical illness on protein metabolism, nutrition therapy in clinical practice, and the function of specific amino acids.

Immunochemotherapy benefits in gastric cancer patients stratified by programmed death-1 ligand-1.

BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1 (PD-L1) has not been investigated. Investigating this might help in triaging candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918 patients with stages II and III gastric cancer, undergoing curative gastrectomy, and receiving adjuvant chemotherapy were enrolled in a prospective database, and the patients were retrospectively reviewed. We classified those patients into four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1, PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition, another independent cohort of 20 patients undergoing radical gastrectomy was prospectively recruited to check their immunological cells of sera before and 2 mo after PSK administration. RESULTS: PSK treatment was an independent prognostic factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per se was not. Administration of PSK prolonged patient survival in stages IIIA and IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative expression of PD-L1, treated with PSK had longer survival than those not treated with PSK (P = 0.033). PSK did not affect the survival of patients with positive expression of PD-L1, (P = 0.421). The percentages of natural killer and natural killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-γ+/CD8+ T cells, were significantly increased in PD-L1 (-) patients treated with PSK. However, these findings were not evident in PD-L1 (+) patients. CONCLUSIONS: PSK treatment preferentially confers a survival gain for patients with stage IIIA/IIIB gastric cancer, especially in the PD-L1 (-) subpopulation.

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.

MART-10, the new brand of 1α,25(OH)2D3 analog, is a potent anti-angiogenic agent in vivo and in vitro.

BACKGROUND: Angiogenesis is the hall marker for cancer growth and metastasis. Thus, anti-angiogenesis emerges as a new way to treat cancer. 1α,25(OH)2D3 is recently getting popular due to the non-mineral functions, which have been applied fore cancer treatment. The newly-synthesized 1α,25(OH)2D3 analog, MART-10, has been proved to be much more potent than 1α,25(OH)2D3 regarding inhibiting cancer cells growth and metastasis without inducing hypercalcemia in vivo. In this study, we aimed to investigate the effect of MART-10 and 1α,25(OH)2D3 on angiogenesis in vitro and in vivo. METHODS AND RESULTS: MART-10 and 1α,25(OH)2D3 were able to repress VEGFA-induced human umbilical vein endothelial cells (HUVECs) migration, invasion and tube formation, but not proliferation, with MART-10 much more potent than 1α,25(OH)2D3. The Chick Chorioallantoic Membrane (CAM) assay and matrigeal angiogenesis assay further confirmed the in vivo more potent anti-angiogenesis effect of MART-10. MART-10 inhibited the VEGFA-induced HUVECs angiogenesis process through downregulation of Akt and Erk 1/2 phosphorylation. The VEGFA-VEGFR2 (VEGF receptor 2) axis is the main signal transducing pathway to stimulate angiogenesis. A positive autocrine manner was found for the first time in HUVECs as treated by VEGFA, which induced VEGFA expression and secretion, and VEGFR2 expression. MART-10 and 1α,25(OH)2D3 were demonstrated to be able to repress this positive autocrine manner, thus inhibiting angiogenesis. CONCLUSIONS: MART-10 and 1α,25(OH)2D3 both are effective anti-angiogenesis agents. Given MART-10 is much more potent than 1α,25(OH)2D3 and active in vivo without obvious side effect, MART-10 should be deemed as a promising anti-cancer agent.

MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D(3) in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells.

Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH)(2)D(3) analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D(3 )(MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH)(2)D(3) in inhibiting cell growth in a dose- and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G(0)/G(1) phase as compared to 1α,25(OH)(2)D(3), possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH)(2)D(3) in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted.

Combined resection and multi-agent adjuvant chemotherapy for desmoplastic small round cell tumor arising in the abdominal cavity: report of a case.

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.