A developed and validated centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method for rapid quantification of unbound lenvatinib in human plasma.

In clinical practice, the determination of unbound drug concentration is very important for dose adjustment and toxicity prediction because only the unbound fraction can achieve a pharmacological effect. A fast, sensitive and accurate analytical method of centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method was developed and applied to allow the quantification of unbound lenvatinib concentration. The application of linear regression analysis was used to examine the effects of centrifugal force, centrifugal time, and protein content on ultrafiltrate volume (Vu). The results indicated that the centrifugal force and centrifugal time have an influence on Vu that is significantly positive (P < 0.05). This developed method with good linearity (r2 = 0.9996), good accuracy (bias % ≤ 2.24 %), good precision (CV % ≤ 7.10 %), and good recovery (95.46 %-106.46 %) was suitable for routine clinical practice and studies. Particularly, the ultrafiltration membrane had no non-specific binding to lenvatinib. The unbound fractions can be separated in just 15 min. This method was applied to quantify clinical samples and to determine the plasma protein binding and unbound fraction of lenvatinib. This study provides a more effective and promising method for determination of unbound lenvatinib. It could be beneficial to measure the unbound concentration of lenvatinib in personalized medicine and therapeutic drug monitoring in routine clinical practice.

Elevated procalcitonin levels in the absence of infection in procalcitonin-secretin hepatocellular carcinoma: A case report.

BACKGROUND: Serum procalcitonin (PCT) is widely used to diagnose bacterial infection and sepsis. However, PCT may be elevated in some neoplasms. It is important to distinguish infection from no infection in such neoplasms. The relationship between hepatocellular carcinoma (HCC) and PCT is unknown. CASE SUMMARY: A 62-year-old male was admitted due to a hepatic lesion of unknown origin. The patient had an elevated PCT level. Infectious diseases were excluded after appropriate examination. He then underwent exploratory laparotomy and a left lateral hepatectomy was performed. The patient recovered with an uneventful postoperative course and PCT level decreased gradually and was normal on day 16. HCC was diagnosed by histopathology and no evidence of infection was observed. Furthermore, immunohistochemical analyses revealed that tumor cells were positive for PCT. CONCLUSION: HCC cells can secrete PCT in the absence of infection and PCT may be used as a marker to monitor the efficacy of tumor therapy.

Nomogram based on CT-derived extracellular volume for the prediction of post-hepatectomy liver failure in patients with resectable hepatocellular carcinoma.

OBJECTIVES: This study aimed to develop and validate a nomogram based on extracellular volume (ECV) derived from computed tomography (CT) for predicting post-hepatectomy liver failure (PHLF) in patients with resectable hepatocellular carcinoma (HCC). METHODS: A total of 202 patients with resectable HCC from two hospitals were enrolled and underwent multiphasic contrast-enhanced CT before surgery. One hundred twenty-one patients from our hospital and 81 patients from another hospital were assigned to the training cohort and the validation cohort, respectively. CT-derived ECV was measured using nonenhanced and equilibrium-phase-enhanced CT images. The nomogram was developed with independent predictors of PHLF. Predictive performance and calibration were assessed by receiver operator characteristic (ROC) analysis and Hosmer-Lemeshow test, respectively. The Delong test was used to compare the areas under the curve (AUCs). RESULTS: CT-derived ECV had a strong correlation with the postoperative pathological fibrosis stage of the background liver (p < 0.001, r = 0.591). The nomogram combining CT-derived ECV, serum albumin (Alb), and serum total bilirubin (Tbil) obtained higher AUCs than the albumin-bilirubin (ALBI) score for predicting PHLF in both the training cohort (0.828 vs. 0.708; p = 0.004) and the validation cohort (0.821 vs. 0.630; p < 0.001). The nomogram showed satisfactory goodness of fit for PHLF prediction in the training and validation cohorts (p = 0.621 and 0.697, respectively). CONCLUSIONS: The nomogram contributes to the preoperative prediction of PHLF in patients with resectable HCC. KEY POINTS: • CT-derived ECV had a strong correlation with the postoperative pathological fibrosis stage of the background liver. • CT-derived ECV was an independent predictor of PHLF in patients with resectable HCC. • The nomogram based on CT-derived ECV showed a superior prediction efficacy than that of clinical models (including Child-Pugh stage, MELD score, and ALBI score).

Sorafenib plus partial splenic embolism for treatment of hepatocellular carcinoma Barcelona stage C combined with hypersplenism: a case series.

BACKGROUND: Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. METHODS: Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. RESULT: Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. CONCLUSION: Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.

Successful laparoscopic treatment for sustained abdominal pain due to fish bone migrating into the neck of the pancreas: a case report and thinking about surgical approach through the literature review.

BACKGROUND: The majority of ingested foreign bodies pass through the gastrointestinal tract smoothly, with less than 1% requiring surgery. Fish bone could perforate through the wall of stomach or duodenum and then migrate to other surrounding organs, like the pancreas and liver. CASE PRESENTATION: We report herein the case of a 67-year-old male who presented with sustained mild epigastric pain. Abdominal computed tomography revealed a linear, hyperdense, foreign body along the stomach wall and pancreatic neck. We made a final diagnosis of localized inflammation caused by a fish bone penetrating the posterior wall of the gastric antrum and migrating into the neck of the pancreas. Upper gastrointestinal endoscopy was performed firstly, but no foreign body was found. Hence, a laparoscopic surgery was performed. The foreign body was removed safely in one piece and was identified as a 3.2-cm-long fish bone. The patient was discharged from the hospital on the fifth day after surgery without any postoperative complications. CONCLUSION: Laparoscopic surgery has proven to be a safe and effective way to remove an ingested fish bone embedded in the pancreas.

Bone Fragment Co-transplantation Alongside Bone Marrow Aspirate Infusion Protects Kidney Transplant Recipients.

Integration of non-vascularized bone grafting and bone marrow aspirate infusion in transplantation may provide clinical benefit. Here we have incorporated bone fragment co-transplantation and bone marrow aspirate infusion (BF-BM) into living kidney transplantation (LKT). Twenty LKT recipients receiving bone fragments and bone marrow aspirates donated from their corresponding donors were enrolled into a retrospective study. A contemporaneous control group was formed of 38 out of 128 conventional LKT recipients, selected using propensity score matching by a 1:2 Greedy algorithm. Ultrasonography, contrast-enhanced ultrasonography (US/CEUS) and SPECT/CT showed that the co-transplanted bone fragments remained viable for 6 months, subsequently shrank, and finally degenerated 10 months post-transplantation. BF-BM resulted in earlier kidney recovery and more robust long-term kidney function. Throughout 5 years of follow-up, BF-BM had regulatory effects on dendritic cells (DCs), T helper (Th1/Th2) cells and regulatory T cells (Tregs). Both alloantigen-specific lymphocyte proliferation and panel reactive antibody levels were negative in all recipients with or without BF-BM. In addition, the BF-BM group experienced few complications during the 5-year follow-up (as did the donors)-this was not different from the controls. In conclusion, BF-BM is safe and benefits recipients by protecting the kidney and regulating the immune response.

Intrahepatic cholangiocarcinoma is more complex than we thought: A case report.

BACKGROUND: Brain metastasis from intrahepatic cholangiocarcinoma is rare. To the best of our knowledge, only a few cases have been reported. The biological behavior was complex, and treatment requires further investigation. CASE SUMMARY: A 62-year-old woman complained of left limb weakness. Abdominal computed tomography showed a 5.0 cm × 5.6 cm lesion in the left lobe of the liver. Tumor markers were normal. Serological analysis indicated absence of hepatitis virus. Brain magnetic resonance imaging revealed a 1.0 cm × 1.3 cm mass in the right frontal lobe. Intrahepatic cholangiocarcinoma with brain metastasis was diagnosed by our liver cancer multidisciplinary team. After sufficient preparation, the patient underwent partial frontal lobotomy and left hemihepatectomy. Histopathological results confirmed that both the lesions were cholangiocarcinoma. Six cycles of gemcitabine combined with S1 were administered. During a 39 mo postoperative follow-up, no sign of local recurrence or distant metastasis was observed. CONCLUSION: This case expands our knowledge concerning the complex and heterogeneous nature of tumor metastasis.

Correction to: A novel organ preservation solution with efficient clearance of red blood cells improves kidney transplantation in a canine model.

[This corrects the article DOI: 10.1186/s13578-018-0226-2.].

Hepatic splenosis: Rare yet important - A case report and literature review.

Hepatic splenosis is an uncommon condition that occurs following traumatic splenic rupture or splenectomy. The case of a 41-year-old male patient with multiple isolated liver masses indistinguishable from primary and metastatic liver tumours is reported. Following laparotomy, the liver lesions were resected and histopathology confirmed a diagnosis of hepatic splenosis. At an 18-month follow-up examination, no abnormalities in routine blood test, liver function, and liver computed tomography (CT) scanning were observed. After review of the literature, the following diagnostic criteria for hepatic splenosis are proposed: (1) a history of splenic trauma or splenectomy; (2) lesion(s) with a surrounding rim, particularly near the liver capsule identified by CT scanning; (3) findings on superparamagnetic iron oxide-enhanced magnetic resonance imaging or technetium-99m heat-damaged red cell scanning; and (4) histopathological findings (needle biopsy or surgical pathology). The following diagnostic process is also proposed: suspect diagnosis when criteria 1 and 2 are met; make diagnosis when criterion 3 is met; confirm diagnosis when criterion 4 is met. Laparotomy is recommended for either diagnosis or treatment when invasive procedures are necessary.

A novel organ preservation solution with efficient clearance of red blood cells improves kidney transplantation in a canine model.

Organ preservation solutions are designed to minimize organ damage during transplantation. A novel preservation solution, WMO-II, was developed to have a low viscosity and to improve microvasculature perfusion for kidneys. In an autologous canine transplantation model, kidney function and recovery were evaluated after organs were flushed and cold-stored with WMO-II or HTK solution, a perfusate currently approved for clinical use. The average number of red blood cells remaining in a single glomerulus after flushing with WMO-II was significantly reduced when compared with HTK solution. Additionally, WMO-II reduced the number of apoptotic bodies in stored kidneys compared to HTK treated tissue after 48 h of cold storage by reducing expression of Caspase-9, BiP, Chop, and Caspase-12. WMO-II solution reduced serum creatinine levels and serum potassium in kidneys stored for 48 h when compared to HTK perfusion. WMO-II preserves kidney function as evidenced by the reduction in serum creatinine and potassium during graft transplantation.

Epstein-Barr virus negative primary hepatic leiomyoma: case report and literature review.

Primary hepatic leiomyoma is a neoplasm of mesenchymal origin and occurs only rarely. Secondary to benign smooth muscle proliferation, it is usually found in adult women and is associated with Epstein-Barr virus (EBV) infection. Here, we report the 29(th) case of primary hepatic leiomyoma with its unique features related to diagnosis, treatment and developmental biology. A 48-year-old man, with an immunocompromised status, complained of pain in the upper quadrant of the abdomen. Serological analysis indicated no presence of hepatitis virus, no human immunodeficiency virus, and no EBV infection. The levels of α-fetoprotein and carcinoembryonic antigen were normal. A mass was detected in segment III of the hepatic lobe by ultrasonography and an abdominal computed tomography scan. Endoscopy had negative findings. Exploratory laparotomy found no existing extrahepatic tumor and left lateral lobectomy was performed. Pathological examination showed the mass to be a typical leiomyoma. The cells were positive for α-smooth muscle actin and desmin, and negative for the makers of gastrointestinal stromal tumor (GIST), including CD117, CD34 and DOG1 (discovered on GIST1). In situ hybridization revealed negative status for EBV-encoded small RNA. After left lateral lobectomy, the patient was not given chemotherapy or radiotherapy. During a 2-year follow-up, no sign of local recurrence or distant metastasis was observed. In conclusion, we report a rare case of primary hepatic leiomyoma in a male patient without EBV infection. Hepatic resection was curative. This case presents data to expand our knowledge concerning the complex and heterogeneous nature of primary liver leiomyoma, indicating that EBV infection is important but neither necessary nor sufficient for the development of primary liver leiomyoma.