Impact of thoracic shape on the surgical outcomes of laparoscopic-assisted living donor hepatectomy.

Background: Although laparoscopic-assisted donor hepatectomy (LADH) has become the definitive procedure for harvesting living donor livers, its surgical outcomes in association with donor body shape have not been elucidated. Methods: The impact of donor factors, including thoracic shape, on LADH outcomes was retrospectively investigated. Thoracic anthropometric data were examined in all LADHs with a left/right graft between 2013 and 2022. Results: The study included 210 LADHs, consisting of 106 left- and 104 right-lobe donors with similar blood loss and similar operation time. Males have greater thoracic depth and greater thoracic width compared with females, respectively. Thoracic depth was associated with graft weight (p < 0.001), blood loss (p < 0.001), and operation time (p < 0.001). On multivariate analyses, blood loss >500 mL and operation time >8 h were associated with graft weight in the left-lobe donors, and blood loss >500 mL was associated with thoracic depth in the right-lobe donors. Conclusion: The greater thoracic depth is associated with massive blood loss in right-lobe donors. Anthropometric parameters might be helpful for estimating LADH outcomes.

Current status of total pancreatectomy with islet autotransplantation for chronic and recurrent acute pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan.

Temporal Single Cell Analysis of Leukemia Microenvironment Identifies Taurine-Taurine Transporter Axis as a Key Regulator of Myeloid Leukemia.

Signals from the microenvironment are known to be critical for development, sustaining adult stem cells, and for oncogenic progression. While candidate niche-driven signals that can promote cancer progression have been identified 1-6 , concerted efforts to comprehensively map microenvironmental ligands for cancer stem cell specific surface receptors have been lacking. Here, we use temporal single cell RNA-sequencing to identify molecular cues from the bone marrow stromal niche that engage leukemia stem cells (LSC) during oncogenic progression. We integrate these data with our RNA-seq analysis of human LSCs from distinct aggressive myeloid cancer subtypes and our CRISPR based in vivo LSC dependency map 7 to develop a temporal receptor-ligand interactome essential for disease progression. These analyses identify the taurine transporter (TauT)-taurine axis as a critical dependency of myeloid malignancies. We show that taurine production is restricted to the osteolineage population during cancer initiation and expansion. Inhibiting taurine synthesis in osteolineage cells impairs LSC growth and survival. Our experiments with the TauT genetic loss of function murine model indicate that its loss significantly impairs the progression of aggressive myeloid leukemias in vivo by downregulating glycolysis. Further, TauT inhibition using a small molecule strongly impairs the growth and survival of patient derived myeloid leukemia cells. Finally, we show that TauT inhibition can synergize with the clinically approved oxidative phosphorylation inhibitor venetoclax 8, 9 to block the growth of primary human leukemia cells. Given that aggressive myeloid leukemias continue to be refractory to current therapies and have poor prognosis, our work indicates targeting the taurine transporter may be of therapeutic significance. Collectively, our data establishes a temporal landscape of stromal signals during cancer progression and identifies taurine-taurine transporter signaling as an important new regulator of myeloid malignancies.

Effects of dietary seaweed on obesity-related metabolic status: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Seaweed is a promising source of anti-obesity agents, including polysaccharides, proteins, polyphenols, carotenoids, and n-3 long-chain polyunsaturated fatty acids. The anti-obesity effects of such compounds may be due to several mechanisms, including inhibition of lipid absorption and metabolism, effect on satiety, and inhibition of adipocyte differentiation. OBJECTIVE: The aim of this study was to assess the evidence from human randomized controlled trials for the effects of seaweed on body-weight status as well as lipid and nonlipid parameters in adults with overweight and obesity. DATA SOURCES: Four databases-Medline, Scopus, Web of Science, and Cochrane Library-were searched from December 2022 to June 2023 using the following key words: Seaweed OR fucoxanthin OR alginates OR fucoidans OR phlorotannin's OR macroalgae OR marine algae AND obesity OR overweight OR BMI OR body mass index. DATA EXTRACTION: Eleven interventional studies (10 parallel and 1 crossover) were extracted. DATA ANALYSIS: Meta-analysis showed a significant effect, favoring the intervention group for BMI (body mass index) (standardized mean difference [SMD]: -0.40; 95% CI: -0.65 to -0.16 kg/m2; P = 0.0013) and percentage of fat mass (SMD: -1.48; 95% CI: -2.66% to -0.30%, P = 0.0138). The results were seen when refined or extracted brown seaweed (BMI) or only refined brown seaweed (% fat mass) were administered to participants for at least 8 weeks. Moreover, a significant overall effect of seaweed supplementation on total cholesterol (SMD: -7.72; 95% CI: -12.49 to -2.95 mg/dL; P = 0.0015) and low-density-lipoprotein cholesterol (SMD: -7.33; 95% CI: -11.64 to -3.02 mg/dL; P < 0.001) was noted. Any significant effects of seaweed on glucose metabolism were not shown. CONCLUSION: Edible seaweed supplementation shows potential for managing obesity and disorders of the blood lipid profile when administered to participants for at least 8 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022378484 (www.crd.york.ac.uk/PROSPERO).

Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.

DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease.

Integrated analyses of the genetic and clinicopathological features of cholangiolocarcinoma: cholangiolocarcinoma may be characterized by mismatch-repair deficiency.

Cholangiolocarcinoma (CLC) is a primary liver carcinoma that resembles the canals of Hering and that has been reported to be associated with stem cell features. Due to its rarity, the nature of CLC remains unclear, and its pathological classification remains controversial. To clarify the positioning of CLC in primary liver cancers and identify characteristics that could distinguish CLC from other liver cancers, we performed integrated analyses using whole-exome sequencing (WES), immunohistochemistry, and a retrospective review of clinical information on eight CLC cases and two cases of recurrent CLC. WES demonstrated that CLC includes IDH1 and BAP1 mutations, which are characteristic of intrahepatic cholangiocarcinoma (iCCA). A mutational signature analysis showed a pattern similar to that of iCCA, which was different from that of hepatocellular carcinoma (HCC). CLC cells, including CK7, CK19, and EpCAM, were positive for cholangiocytic differentiation markers. However, the hepatocytic differentiation marker AFP and stem cell marker SALL4 were completely negative. The immunostaining patterns of CLC with CD56 and epithelial membrane antigen were similar to those of the noncancerous bile ductules. In contrast, mutational signature cluster analyses revealed that CLC formed a cluster associated with mismatch-repair deficiency (dMMR), which was separate from iCCA. Therefore, to evaluate MMR status, we performed immunostaining of four MMR proteins (PMS2, MSH6, MLH1, and MSH2) and detected dMMR in almost all CLCs. In conclusion, CLC had highly similar characteristics to iCCA but not to HCC. CLC can be categorized as a subtype of iCCA. In contrast, CLC has characteristics of dMMR tumors that are not found in iCCA, suggesting that it should be treated distinctly from iCCA. © 2024 The Pathological Society of Great Britain and Ireland.

Development of a non-destructive depth-selective quantification method for sub-percent carbon contents in steel using negative muon lifetime analysis.

The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20-1.03 wt% depth-selectively, without sample destruction.

Trends in long-term outcomes of patients with HCV-associated hepatocellular carcinoma after hepatectomy: A comparison before and after introduction of direct-acting antivirus therapy.

Backgrounds: The success of direct-acting antiviral (DAA) therapy provides a cure for patients chronically infected with hepatitis C virus (HCV); however, outcomes after hepatectomy for HCV-associated hepatocellular carcinoma (HCC) before and after DAA introduction remain poorly studied. Methods: Patients who underwent R0/R1 hepatectomy for HCV-associated HCC were retrospectively analyzed. Two time periods were defined: Pre-DAA (2007-2011, December 2013 was defined as the end of follow-up) and Post-DAA groups (2014-2018, December 2020 was defined as the end of follow-up). Propensity score matching (PSM) analyses were performed to highlight the effect of DAA therapy. Results: A total of 155 patients with HCV-associated HCC were included in this study (Pre-DAA group, n = 103 and post-DAA group, n = 52). In the Post-DAA group, DAA therapy was performed in 26 patients (50.0%), and all of these patients achieved sustained virologic response (SVR) (preoperative SVR, n = 7; postoperative SVR, n = 19). There was no significant difference between the two groups regarding surgical settings and tumor pathology. There was no significant difference in the 5-year overall survival (OS) rate (61.1% and 64.8%, pre- and post-DAA group, respectively, p = 0.441); meanwhile, the 5-year recurrence-free survival (RFS) rate in the post-DAA group was better than the pre-DAA group (21.1% and 40.2%, p = 0.073) with a trend toward significance. After PSM except for the postoperative SVR status, there were no significant differences in OS (p = 0.586) and RFS (p = 0.888). Conclusions: This study showed that survival outcomes were not changed in hepatectomized cases of HCV-associated HCC before and after the introduction of DAA therapy.

Left-sided major hepatectomy with en bloc resection of the hepatoduodenal ligament utilizing a liver-transection first approach: A video vignette.

TECHNIQUE: Hepatoduodenal ligamentectomy (HL) is a challenging surgery for advanced perihilar cholangiocarcinoma extensively invading the hepatoduodenal ligament1-3. A liver-transection first approach in HL is a no-touch technique wherein liver transection is performed first, and the affected liver and hepatoduodenal ligament are removed en bloc. This approach allows for the early assessment of resectability and feasibility of vascular reconstruction4. RESULTS: This video shows a 57-year-old man with advanced intrahepatic cholangiocarcinoma in the left hepatic lobe, which had directly invaded the perihilar region and the hepatoduodenal ligament via lymph node metastasis. The lymph node was extensively invasive into both the proper hepatic artery and portal vein. The case was initially deemed unresectable, but after three months of chemotherapy, conversion surgery was considered feasible. The common hepatic artery and gastroduodenal artery and then the common bile duct and main trunk of portal vein were secured at the pancreatic superior border. Hepatic dissection was performed along the Cantlie line. The right Glissonean pedicle was secured, including the right hepatic duct, right hepatic artery and right portal vein, and the operation was deemed feasible. The portal vein was dissected and reconstructed using the right external iliac vein. The left and caudate lobe with the middle hepatic vein and hepatoduodenal ligament were resected en bloc. Subsequentially, the common hepatic artery and right hepatic artery were reconstructed using the jejunal artery. CONCLUSION: The liver-transection first approach allowed us to determine the resectability of en bloc resection of the hepatoduodenal ligament at an early stage of surgery.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

Feasible living donor liver transplantation for patients on chronic hemodialysis: a multicenter study in East Asian countries.

PURPOSES: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD. METHODS: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed. RESULTS: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%). CONCLUSION: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD.

Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein.

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.

Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular-cholangiocarcinoma.

AIM: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC-CCA remains to be elucidated. METHODS: Whole-exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC-CCAs. The whole-exome analyses and clinicopathological information were integrated. RESULTS: TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC-CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC-CCA tumors. Recurrent and co-occurrent HCC tumors in the same patients with cHCC-CCA had either common or different mutation patterns from the primary cHCC-CCA tumors in each case. CONCLUSIONS: The study suggested that there were two subtypes of cHCC-CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC-CCA was derived from an identical clone.

Is the anterior approach recommended for liver resection of hepatocellular carcinoma? A systematic review and meta-analysis.

BACKGROUND/PURPOSE: The anterior approach (AA) in liver resection has proven more effective with regard to short-term outcomes than the conventional approach (CA). However, its superiority over the CA concerning long-term outcomes remains unclear. This meta-analysis compared the short- and long-term outcomes of the AA and CA. METHODS: Databases, including MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials, were searched to identify studies comparing the AA and CA for hepatocellular carcinoma (HCC) liver resection. The primary outcomes were the in-hospital mortality, in-hospital morbidity, disease-free survival (DFS), and overall survival (OS). Secondary outcomes were operative time, blood loss, blood transfusion, R0 rate, and length of hospital stay. RESULTS: Ten studies involving 1369 patients were included (AA, n = 595; CA, n = 774). Despite no significant differences in the in-hospital mortality or morbidity, the AA demonstrated a superior DFS (hazard ratio [HR], 0.63; 95% confidence interval [CI]: 0.51-0.77) and OS (HR, 0.56; 95% CI: 0.48-0.65) and was associated with a longer operative time, less blood loss, and less transfusion than the CA. No marked differences in other outcomes were noted. CONCLUSIONS: The AA for HCC liver resection helped reduce blood loss and need for transfusion, improving the DFS and OS.

Dual Lumen Microcatheter in Percutaneous Biliary Drainage for Postoperative Bile Leakage: A Case Report.

Percutaneous biliary intervention is widely accepted as an effective and safe treatment for various types of bile duct diseases. We present the case of a 44-year-old woman who developed bile leakage after a living-donor liver transplantation for locally advanced cholangiocarcinoma. A percutaneous drainage tube was placed in the segment 8 bile duct via the blind end of the jejunum. However, the bile leakage was unchanged. Bile leakage from the right posterior hepatic duct was suspected. Using a dual lumen microcatheter, a percutaneous drainage tube was placed in the segment 7 bile duct via the blind end of the jejunum, which reduced the bile leakage. These results suggest that a dual lumen microcatheter is a valuable tool for navigating the biliary tree during difficult percutaneous biliary interventions.

Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans.

Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.

Edible Red Seaweed Hypnea asiatica Ameliorates High-Fat Diet-Induced Metabolic Diseases in Mice.

Metabolic diseases, including obesity, diabetes, and fatty liver disease, are dramatically increasing around the world. Seaweed is low in calories and rich in many active ingredients that are necessary for maintaining good health, and is expected to be effective for preventing metabolic diseases. The purpose of this study was to examine the effects of a traditional Japanese edible seaweed Hypnea asiatica (H. asiatica) on obesity, using a mouse model. H. asiatica was dried and powdered, mixed with a high-fat diet, and fed to male C57BL/6J mice for 13 weeks. On the last day of the experiment, blood samples were collected under anesthesia and biochemical parameters such as lipids and adipokines were measured. Liver and adipose tissue were excised, weighed, and oxidant/antioxidant parameters were measured. Some mice were perfused with a fixative solution containing formalin, and tissue specimens were prepared. A glucose tolerance test was used to assess insulin resistance. The inhibition of lipase activity was evaluated in vitro. Thirteen-week supplementation with H. asiatica suppressed body weight gain, body fat accumulation, and blood glucose levels. H. asiatica also improved fatty liver and hypercholesterolemia, and reduced the oxidant and inflammatory parameters of serum and liver. H. asiatica increased fecal triglyceride excretion and polyphenol-rich ethanol extract of H. asiatica inhibited lipase activity in vitro. These results suggest that polysaccharides and polyphenols in H. asiatica may ameliorate obesity and diabetes by inhibiting intestinal fat absorption and reducing oxidative stress and inflammation. H. asiatica may be useful in preventing metabolic diseases such as obesity, diabetes, and fatty liver.

Anaphylactic shock due to intra-articular injection of diclofenac etalhyaluronate sodium: A case report.

Background: Anaphylactic shock of diclofenac etalhyaluronate agent can be prolonged and recurrent. However, its reports are rare, and consequently, its method of management remains to be established. Case Presentation: A 65-year-old woman received an intra-articular injection of diclofenac and hyaluronate. After 20 min, systemic urticaria and severe hypotension developed after walking. After an intramuscular adrenaline injection, she was transferred to our hospital. Despite administration of continuous noradrenaline and adrenaline, hypotension persisted. Seven hours after the joint injection, 25 mL of knee joint fluid was aspirated under ultrasound guidance. Mobilization was performed 24 h after joint injection. However, urticaria rapidly spread after standing. At 45 and 46 h after joint injection, we confirmed that no symptoms, including urticaria, recurred after walking. Conclusion: Anaphylactic shock due to intra-articular injection of diclofenac etalhyaluronate is prolonged and requires extended observation. Aspiration of joint fluid may be one of the treatment options.