Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Universal visualization of crystalline orientation for black phosphorus by angle-resolved polarized photoacoustic microscopy.

Anisotropic two-dimensional (2D) materials, such as black phosphorus (BP), normally possess unique directional in-plane electrical, optical, and thermal properties that are highly correlated with their crystalline orientations. Nondestructive visualization of their crystalline orientation is an indispensable premise for the 2D materials to harness their distinctive strengths in optoelectronic and thermoelectric applications. Here, by photoacoustically recording the anisotropic optical absorption variation under linearly polarized laser beams, an angle-resolved polarized photoacoustic microscopy (AnR-PPAM) is developed, capable of non-invasively determining and visualizing BP's crystalline orientation. We theoretically deduced the physical relationship between the crystalline orientation and polarized photoacoustic (PA) signals, and experimentally proved the ability of AnR-PPAM to universally visualize BP's crystalline orientation regardless of its thickness, substrate, and encapsulation layer. This method provides a new, to the best of our knowledge, strategy for crystalline orientation recognition of 2D materials with flexible measurement conditions, prefiguring important potential for the applications of anisotropic 2D materials.

Prognostic value of platelet distribution width to lymphocyte ratio in patients with hepatocellular carcinoma following hepatectomy.

BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.

Preoperative prediction model for microvascular invasion in HBV-related intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. METHODS: Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. RESULTS: Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765-0.894) and 0.729 (95%CI: 0.706-0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. CONCLUSION: Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

Background & Aims: To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Methods: Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Results: Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). Conclusion: A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Compressed single-shot 3D photoacoustic imaging with a single-element transducer.

Three-dimensional (3D) photoacoustic imaging (PAI) can provide rich information content and has gained increasingly more attention in various biomedical applications. However, current 3D PAI methods either involves pointwise scanning of the 3D volume using a single-element transducer, which can be time-consuming, or requires an array of transducers, which is known to be complex and expensive. By utilizing a 3D encoder and compressed sensing techniques, we develop a new imaging modality that is capable of single-shot 3D PAI using a single-element transducer. The proposed method is validated with phantom study, which demonstrates single-shot 3D imaging of different objects and 3D tracking of a moving object. After one-time calibration, while the system could perform single-shot 3D imaging for different objects, the calibration could remain effective over 7 days, which is highly beneficial for practical translation. Overall, the experimental results showcase the potential of this technique for both scientific research and clinical applications.

NIR-II femtosecond laser ignites MXene as photoacoustic bomb for continuous high-precision tumor blasting.

Recently, photoacoustic (PA) cavitation-mediated therapy has become the focus of research owing to its advantage of inhibiting drug or radiation resistance; however, its application is limited because it relies on nanodroplets with one-time action. Herein, we demonstrate a femtosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics using niobium carbide (Nb2C) coated with polyvinylpyrrolidone-40000 (PVP), producing sustainable PA cavitation with non-phase-change nanoprobes, which effectively gets rid of the dependence on nanodroplets, guaranteeing multiple treatments. Under femtosecond (fs) laser irradiation, given that the thermal confinement regime could be well satisfied, the Nb2C-PVP nanosheets (NSs) were quickly heated, forming localized overheated nanospots with the temperature exceeding the phase-transition threshold of the surroundings, leading to precise cavitation and explosion at the tumor sites. The experiments at the cellular level showed the significant anti-tumor effects of this method. Notably, the mouse model experiments showed a relative tumor volume inhibition rate of more than 90%, demonstrating the high precision and good efficacy of the proposed anti-tumor method. This method provides a sustainable and highly effective strategy for PA theranostics, indicating its great potential for clinical applications.

Quantitative 3D Temperature Rendering of Deep Tumors by a NIR-II Reversibly Responsive W-VO2@PEG Photoacoustic Nanothermometer to Promote Precise Cancer Photothermal Therapy.

Accurately monitoring the three-dimensional (3D) temperature distribution of the tumor area in situ is a critical task that remains challenging in precision cancer photothermal (PT) therapy. Here, by ingeniously constructing a polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO2@PEG) photoacoustic (PA) nanothermometer (NThem) that linearly and reversibly responds to the thermal field near the human-body-temperature range, the authors propose a method to realize quantitative 3D temperature rendering of deep tumors to promote precise cancer PT therapy. The prepared NThems exhibit a mild phase transition from the monoclinic phase to the rutile phase when their temperature grows from 35 to 45 °C, with the optical absorption sharply increased ∼2-fold at 1064 nm in an approximately linear manner in the near-infrared-II (NIR-II) region, enabling W-VO2@PEG to be used as NThems for quantitative temperature monitoring of deep tumors with basepoint calibration, as well as diagnostic agents for PT therapy. Experimental results showed that the temperature measurement accuracy of the proposed method can reach 0.3 °C, with imaging depths up to 2 and 0.65 cm in tissue-mimicking phantoms and mouse tumor tissue, respectively. In addition, it was verified through PT therapy experiments in mice that the proposed method can achieve extremely high PT therapy efficiency by monitoring the temperature of the target area during PT therapy. This work provides a potential demonstration promoting precise cancer PT therapy through quantitative 3D temperature rendering of deep tumors by PA NThems with higher security and higher efficacy.

Ultrafast photoacoustic cavitation pumped by picosecond laser for high-efficient and long-term shockwave theranostics.

Photoacoustic (PA) theranostics is a new emerging field that uniquely combines diagnosis and treatment in one modality. However, its current status is compromised by the indispensable dependence on nonreversible phase-change nanoprobes that provides one-time-only action. Here, we demonstrate a picosecond-laser-pumped ultrafast PA cavitation technique for highly efficient shockwave theranostics, guaranteeing sustained PA cavitation by using non-phase-change nanoprobes. Theoretical simulations validate that, when compressing the excitation laser pulse width to hundred-picosecond, the thermal confinement effects of a conventional nanoprobe will induce transient heating of the extremely thin surrounding liquid layer of the nanoprobes beyond its cavitation point in a localized area at nanoscale, resulting in intense cavitation and PA shockwaves by the environment rather than the nanoprobes. Both cellular and mouse model experiments have demonstrated the highly effective anti-tumor effects. This method provides a sustainable, reproducible, and highly effective strategy for PA theranostics, prefiguring great potential for the clinical applications.

Intragastric fish bones migrate into the liver: A case report.

BACKGROUND: A foreign body in the digestive tract is a common disease in the clinic. However, it is rare for a foreign body to migrate into the liver. Most patients are diagnosed before or after perforation of the digestive tract. Laparoscopic removal of intrahepatic foreign bodies is an effective treatment method. CASE SUMMARY: A 55-year-old male patient was admitted to the hospital due to fever for 3 d, in addition to pain and discomfort in the right side of his waist. After admission, abdominal computed tomography showed a foreign body in the liver, and gastroscopy did not indicate obvious erosion or ulcers. The patient then underwent laparoscopic surgery. During the operation, an abscess was seen near the gastric antrum and between the caudate lobes of the liver. It was approximately 30 mm × 31 mm × 23 mm in size. The abscess was cut open, and a fish bone was found inside. The fish bone had penetrated the liver and was successfully removed. It was confirmed that the fish bone migrated from the stomach to the liver. CONCLUSION: Although intrahepatic foreign bodies are rare, they should be diagnosed and treated as early as possible to avoid serious complications such as intrahepatic abscess, which may lead to liver resection and even life-threatening events.

Survival Benefits From Adjuvant Lenvatinib for Patients With Hepatocellular Carcinoma and Microvascular Invasion After Curative Hepatectomy.

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P < .05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P = .001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P = .016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival.

Acute pancreatitis as a rare complication of gastrointestinal endoscopy: A case report.

BACKGROUND: Acute pancreatitis is an uncommon complication of gastrointestinal endoscopy, especially if the patient has none of the common risk factors associated with pancreatitis; such as alcoholism, gallstones, hypertriglyceridemia, hypercalcemia or the use of certain drugs. CASE SUMMARY: A 56-year-old female patient developed abdominal pain immediately after the completion of an upper gastrointestinal endoscopy. The pain was predominantly in the upper and middle abdomen and was persistent and severe. The patient was diagnosed with acute pancreatitis. Treatment included complete fasting, octreotide injection prepared in a prefilled syringe to inhibit pancreatic enzymes secretion, ulinastatin injection to inhibit pancreatic enzymes activity, esomeprazole for gastric acid suppression, fluid replacement and nutritional support. Over the next 3 d, the patient's symptoms improved. The patient remained hemodynamically stable throughout hospitalization and was discharged home in a clinically stable state. CONCLUSION: Pancreatitis should be considered in the differential diagnosis of abdominal pain after upper and lower gastrointestinal endoscopy.

Gastric syphilis mimicking gastric cancer: A case report.

BACKGROUND: The nonspecific clinical, radiological and pathological characteristics of gastric syphilis can establish it as an imitator of other gastric diseases. The absence of primary or secondary lubricating lesions should not prevent consideration of gastric syphilis. CASE SUMMARY: A 63-year-old female patient presented to the hospital with dull pain in the middle and upper abdomen without apparent cause for one week, which was aggravated for two days. The patient had been sexually active with the same male partner for the past years, but her partner was promiscuous. Abdominal contrast-enhanced computed tomography (CT) and positron emission tomography/CT suggested gastric cancer. The gastroscopy revealed an antral gastric ulcer with gastric retention, and also suggested gastric cancer. But no cancer cells were found in the biopsies taken during the two gastroscopies. Treponema pallidum (T. pallidum) antibodies: ELISA positive, rapid plasma reagin titer 1:16. Hematoxylin and eosin (HE) stain showed macrophage infiltration in the lamina propria. Numerous spirochetes were observed by immunohistochemical staining using a monoclonal antibody against T. pallidum. The patient was finally diagnosed with gastric syphilis. CONCLUSION: Only a few cases of gastric syphilis have been misdiagnosed as gastric cancer. Penicillin can relieve symptoms of gastric syphilis.

Gastroesophageal varices in a patient presenting with essential thrombocythemia: A case report.

BACKGROUND: Gastroesophageal varices are a rare complication of essential thrombocythemia (ET). ET is a chronic myeloproliferative neoplasm (MPN) characterized by an increased number of blood platelets. CASE SUMMARY: A 46-year-old woman, who denied a history of liver disease, was admitted to our hospital on presentation of hematemesis. Laboratory examination revealed a hemoglobin level of 83 g/L, and a platelet count of 397 × 109/L. The appearance of gastric and esophageal varices with red colored signs as displayed by an urgent endoscopy was followed by endoscopic variceal ligation and endoscopic tissue adhesive. Abdominal computed tomography revealed cirrhosis, marked splenomegaly, portal vein thrombosis and portal hypertension. In addition, bone marrow biopsy and evidence of mutated Janus kinase 2, substantiated the onset of ET. The patient was asymptomatic with regular routine blood testing during the 6-mo follow-up period. Therefore, in this case, gastroesophageal varices were induced by ET. CONCLUSION: MPN should be given considerable attention when performing differential diagnoses in patients with gastroesophageal varices. An integrated approach such as laboratory tests, radiological examination, and pathological biopsy, should be included to allow optimal decisions and management.

Inhibition of endothelin-1 and hypoxia-induced pulmonary pressor responses in the rat by a novel selective endothelin-A receptor antagonist, di-n-butylaminocarbamyl-L-leucyl-D-tryptophanyl-D-4-chloro-Phe.

Pulmonary hypertension is a kind of disease associated with a very high rate of mortality, and there are not many effective drugs for the treatment. Today, endothelin (ET)-1 receptor antagonists were proved to be effective in the treatment of pulmonary hypertension. Aiming at developing new endothelin-A receptor (ETA) antagonist for treatment of pulmonary hypertension, di-n-butylaminocarbamyl-L-leucyl-D-tryptophanyl-D-4-chloro-Phe, named GF063, was synthesized at base of selective ETA receptor antagonist BQ485 and selected for the further pharmacological characterization. The preliminary pharmacodynamics of GF063 was evaluated by radioligand receptor binding assay and test of antivasoconstriction effects in vitro and in vivo. The integrative pharmacodynamics was evaluated in hypoxia-induced rat pulmonary hypertension. In vitro, GF063 bound to ETA receptor with 100,000-fold higher affinity than to ETB receptor. GF063 concentration dependently inhibited contraction of isolated rat aortic ring induced by ET-1 and shifted the cumulative concentration-contraction response curve to right with no change in the maximal response. In vivo, GF063 inhibited the increase of mean systemic arterial pressure induced by ET-1 in anesthetized rat. In hypoxia-induced rat pulmonary hypertension model, pretreatment with GF063 (40 mg/kg, s.c.) significantly decreased pulmonary artery pressure and right ventricular hypertrophy, also significantly inhibited the increase of ET-1 level in lung, improved hemodynamics, and alleviated the wall thickness of pulmonary vessels. This study indicated that GF063, as a selective ETA receptor antagonist, could inhibit vasoconstriction effects in vivo and in vitro, could prevent pulmonary hypertension induced by hypoxia, and may have great potential to be developed as a new drug of antipulmonary hypertension.

[Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema].

OBJECTIVE: To identify the disease-causing gene in a four-generation Chinese family with 9 members affected with primary congenital lymphoedema (PCL, also known as Milroy disease). METHODS: Linkage analysis was performed with a few microsatellite markers flanking the candidate genetic loci for PCL, including 3 known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3 gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of the VEGFR3 gene was performed in all family members. RESULTS: The disease gene in the family was mapped to chromosome 5q35.3 with a maximum Lod score of 2.07. Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at nucleotide 3341, resulting in p.Pro1114Leu mutation. The p.Pro1114Leu mutation co-segregated with all affected individuals in the family. CONCLUSION: This study identified a C3341T (p.Pro1114Leu) mutation in the VEGFR3 gene in a Chinese family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.