Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery. However, the preoperative regimen of ICG administration was still controversial. Factors associated with tumor fluorescence staining effect were unclear. AIM: To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment. METHODS: To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included. Blood laboratory tests were completed within 1 wk before surgery. All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging. ImageJ software was used to measure the fluorescence intensity values of regions of interest. Correlation analysis was used to identify risk factors. A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence. RESULTS: There were 110 patients who were enrolled in this study from January 2019 to January 2021. The mean values of fluorescence intensity of liver background (FI-LB), fluorescence intensity of gallbladder, and fluorescence intensity of target area were 18.87 ± 17.06, 54.84 ± 33.29, and 68.56 ± 36.11, respectively. The receiver operating characteristic (ROC) curve showed that FI-LB was a good indicator for liver clearance ability [area under the ROC curve (AUC) = 0.984]. Correlation analysis found pre-operative aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, adenosine deaminase, and lactate dehydrogenase were positively associated with FI-LB and red blood cell, cholinesterase, and were negatively associated with FI-LB. Total laboratory risk score (TLRS) was calculated according to ROC curve (AUC = 0.848, sensitivity = 0.773, specificity = 0.885). When TLRS was greater than 6.5, the liver clearance ability of ICG was considered as poor. CONCLUSION: Preoperative laboratory blood indicators can predict hepatic ICG clearance ability. Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis.

BACKGROUND: Information on older patients with hospital-acquired acute kidney injury (HA-AKI) and use of drugs is limited. AIM: This study aimed to assess the clinical characteristics, drug uses, and in-hospital outcomes of hospitalized older patients with HA-AKI. METHODS: Patients aged ≥65 years who were hospitalized in medical wards were retrospectively analyzed. The study patients were divided into the HA-AKI and non-AKI groups based on the changes in serum creatinine. Disease incidence, risk factors, drug uses, and in-hospital outcomes were compared between the groups. RESULTS: Of 26,710 older patients in medical wards, 4,491 (16.8%) developed HA-AKI. Older patients with HA-AKI had higher rates of multiple comorbidities and Charlson Comorbidity Index score than those without AKI (p < 0.001). In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05). The proportions of patients with critical illness, use of nephrotoxic drugs, and the requirements of intensive care unit treatment, cardiopulmonary resuscitation, and dialysis as well as in-hospital mortality and hospitalization duration and costs were higher in the HA-AKI than the non-AKI group; these increased with HA-AKI severity (all p for trend <0.001). With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (p < 0.001). Moreover, HA-AKI incidence (adjusted odds ratio [OR], 10.26; 95% confidence interval (CI), 8.27-12.74; p < 0.001), and nephrotoxic drugs exposure (adjusted OR, 1.76; 95% CI, 1.63-1.91; p < 0.001) had an association with an increased in-hospital mortality risk. CONCLUSION: AKI incidence was high among hospitalized older patients. Older patients with HA-AKI had worse in-hospital outcomes and higher resource utilization. Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk.

Comprehensive analysis of natural polysaccharides from TCMs: a generic approach based on UPLC-MS/MS.

Here, we report a new application using liquid chromatography-electrospray mass spectrometry (UHPLC-ESI-MS) using aldononitrile acetate derivatives for simultaneous baseline separation and detection of eight neutral saccharides, two uronic acids, one ketose, and eight alditols within 14 min. The separation was performed on a Cortecs C18 column using acetonitrile (A) and water (B) as the mobile phase with gradient elution. The target components were detected in selected ion monitoring (SIM) mode by mass spectrometry with an electrospray ionization (ESI) source operating in positive ionization mode. A comparison with traditional methods was used to determine the validity of the results. The UHPLC-ESI-MS method was used for quantitative analysis of free carbohydrates in water extracts of Crataegus pinnatifida as well as determination of Polygonatum cyrtonema and Glossy ganoderma monosaccharides in polysaccharides. The results demonstrate that this protocol is a comprehensive and effective technique for qualitative and quantitative analysis of plant polysaccharides from TCMs.

Functional anatomical hepatectomy guided by indocyanine green fluorescence imaging in patients with localized cholestasis: Report of four cases.

BACKGROUND: Liver cancer is a malignant tumor with a high incidence. At present, the most effective treatment is laparoscopic hepatectomy (LH). Indocyanine green fluorescence imaging (ICG-FI) has become an important tool in LH, and the most common fluorescent types of tumors are total fluorescence, partial fluorescence, and rim fluorescence. CASE SUMMARY: We presented four cases of LH guided by ICG-FI in which we also observed the fourth special fluorescent type. When the tumor or intrahepatic stone compresses the adjacent bile duct to cause local cholestasis, the liver segment or subsegment with obstructed bile drainage will show strong fluorescence. Complete removal of the lesion together with the fluorescent liver parenchyma may help reduce the risk of tumor or stone recurrence. CONCLUSION: This type of partial fluorescence can indicate local biliary compression, and the resection method is related to bile drainage, which may be called functional anatomical hepatectomy and ensures radical resection of the lesion.

Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management.

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.

Mining lycodine-type alkaloid biosynthetic genes and genetic markers from transcriptome of Lycopodiastrum casuarinoides.

Objective: Lycopodiastrum casuarinoides, a fern of the Lycopodiaceae family, is a traditional Chinese medicine, which has similar efficacy to that of Huperzia serrata in treating rheumatoid arthritis (RA). However, they are different in the contents and compositions of lycopodium alkaloids. In this study, the biosynthesis related genes of lycopodium alkaloids and genetic markers are discovered in L. casuarinoides transcriptome. Methods: The plant of L. casuarinoides was collected and was subjected to the RNA isolation, cDNA library construction, high throughput RNA sequencing and bioinformatics analysis. Results: Totally 124, 524 high-quality unigenes were assembled from RNA sequencing reads, with an average sequence length of 601 bp. Among the L. casuarinoides transcripts, 61,304 shared the significant similarity (E-value < 10-5) with existing protein sequences in the public databases. From 124,524 unigenes, 47,538 open reading frames (ORFs) were predicted. Based on the bioinformatics analysis, all possible enzyme genes involved in the lycodine-type alkaloids biosynthetic pathway of L. casuarinoides were identified, including lysine decarboxylase (LDC), primary amine oxidase (PAO), malonyl-CoA decarboxylase, etc. Sixty-four putative cytochrome p450 (CYP) and 827 putative transcription factors were selected from the transcriptome unigenes as the candidates of lycodine-type alkaloids biosynthesis modifiers. Furthermore, 13,352 simple sequence repeats (SSRs) were identified from 124,524 unigenes, of which dinucleotide motifs AG/CT were the most abundant (50.1%). Meanwhile, we confirmed the amplification effectiveness of 25 PCR primer pairs for randomly selected SSRs. Conclusion: We obtained the comprehensive transcriptomic information from the high throughput RNA sequencing and bioinformatics analysis, which provided a valuable resource of transcript sequences of L. casuarinoides in public databases.

Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer.

AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with (125)iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body and tail of 9 patients, was found to be unresectable during operation. Diagnosis of pancreatic cancer was made through intraoperative biopsy. Patients were treated with FRA combined with (125)iodine seed implantation. In brief, a RFA needle was placed, which was confirmed by intraoperative ultrasound to decrease the potential injury of surrounding vital structures, a (125)iodine seed was implanted near the blood vessels and around the tumor border followed by bypass palliative procedure (cholangio-jejunostomy and/or gastrojejunostomy) in 29 patients. RESULTS: The serum CA 19-9 level was decreased from 512 ± 86 U/mL before operation to 176 ± 64 U/mL, 108 ± 42 U/mL and 114 ± 48 U/mL, respectively, 1, 3 and 6 mo after operation (P < 0.05). The pain score on day 7 after operation, 1 and 3 mo after combined therapy was decreased from 5.86 ± 1.92 before operation to 2.65 ± 1.04, 1.65 ± 0.88 and 2.03 ± 1.16, respectively, after operation (P < 0.05). The rate of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) in 32 patients was 21.8% (7/32), 56.3% (18/32), 15.6% (5/32) and 6.3% (2/32), respectively, 6 mo after operation, with a median overall survival time of 17. 5 mo. The median survival time of patients at stage III was longer than that of those at stage IV (19 mo vs 10 mo, P = 0.0026). The median survival time of patients who received and did not receive chemotherapy after operation was 20 mo and 16 mo, respectively (P = 0.0176). Of the 32 patients, 3 (10.6%) experienced postoperative complications including transient biliary leaks in 2 patients and acute pancreatitis in 1 patient. All the patients recovered well after conservative support treatment. CONCLUSION: Intraoperative RFA combined with (125)iodine seed implantation is a feasible and safe procedure for unresectable pancreatic cancer with acceptable minor complications, and can prolong the survival time of patients, especially those at stage III.

[Mechanism of laparoscopic adjustable gastric banding in the treatment of obesity with type 2 diabetes mellitus].

OBJECTIVE: To explore the mechanism of laparoscopic adjustable gastric banding (LAGB) in the treatment of obese patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 20 patients with obesity and T2DM were treated with LAGB. During the postoperative 1, 3, 6, 9, 12 months, the body weight changes were monitored and body mass indices (BMI) were calculated. The serum levels of leptin, GLP-1, and ghrelin were examined preoperatively and 1, 3, 6, 9, 12 months after LAGB using enzyme-linked-immunosorbent assay (ELISA). At the same time, the fasting serum insulin (FINS), C-peptide, glycated hemoglobin (HbA1c) levels were examined by electrochemiluminescence and the level of fasting blood glucose (FBG) was tested with oxidase test. RESULTS: At postoperatively 12 months, all the 20 patients lost weight. The mean body weight decreased from (108 + or - 18) kg to (71 + or - 16) kg (P<0.05) and BMI decreased from 38 + or - 5 to 29 + or - 6 (P<0.05). The HOMA-IR decreased from (12.8 + or - 7.4) to (3.4 + or - 2.0) (P<0.01). The serum ghrelin level increased from (7.8 + or - 1.9) microg/L to (11.6 + or - 2.6) microg/L (P<0.01). The serum leptin level declined from (24.9 + or - 13.7) microg/L to(12.9 + or - 5.1) microg/L (P<0.01). The serum GLP-1 level increased from (0.58 + or - 0.12) microg/L to(0.80 + or - 0.06) microg/L (P<0.01). After LAGB, there were positive correlations between serum leptin level and FBG, FINS, HbA1c,and C-peptide level. Serum ghrelin and GLP-1 were negatively correlated with FBG, FINS, HbA1c,C-peptide. CONCLUSIONS: LAGB is effective in treatment of obesity patients with T2DM. The mechanism may be associated with the increase of serum GLP-1 and ghrelin and the decrease of serum leptin and insulin resistance.

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection.

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-gamma by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naïve T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4(+)CD25(high)Foxp3(+) regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Primary carcinoid tumor of the gallbladder: a case report and brief review of the literature.

BACKGROUND: Primary carcinoid tumor of the gallbladder is rare and comprises less than 1% of all carcinoid tumors. Preoperative diagnosis of carcinoid tumor of the gallbladder is difficult. The imageology findings are similar to those in other gallbladder cancers. CASE PRESENTATION: A 46-year-old woman was hospitalized with a preoperative diagnosis of gallbladder carcinoma, The patient was referred for surgical opinion and laparotomy was subsequently performed. A 4 x 5 cm mass was found within the gallbladder, located on the free surface of the body and fundus of the gallbladder. Neither metastases nor direct invasion to the liver was found. The entire mass and gallbladder were excised and intact. Histologically, the tumor consisted of small oval cells with round-to-oval neclei and tumor cells formed small nodular, trabeculare and acinar structures. The tumor showed moderate pleomorphism with scattered mitotic figures, but no definite evidence of vascular permeation, perineural invasion or lymphatic permeation was seen. The tumor cells invaded the mucosa extensively, and some penetrated the muscular layer but not through the serosa of the gallbladder into the liver. Immunohistochemical studies revealed strong positive reaction for chromogranin A and NSE. This lesion was proved to be a primary carcinoid tumor of the gallbladder. A brief review of literature, clinical feature, pathology and treatment of this rare disease was discussed. CONCLUSION: Primary carcinoid tumor of the gallbladder is uncommon. The definite diagnosis is often made on histopathological results after surgery.

[Impact of novel negative immunoregulatory dendritic cells on regulatory T cells in cardiac allograft recipient rats].

AIM: To investigate the effect of recipient dendritic cells (DC) loaded with PUVA-treated donor splenic lymphocytes (PUVA-SP) on CD4(+) CD25(+) regulatory T cells (Treg) and the survival time of cardiac allograft in rats. METHODS: Cardiac allografts from DA donor rats were transplanted into LEW recipient rats. Donor splenic lymphocytes were treated with 8-methoxypsoralen plus UVA irradiation (PUVA). Recipient bone marrow-derived DCs were co-cultured with PUVA-treated donor splenic lymphocytes (PUVA-SP) and the phenotype of the treated DCs was analyzed with flow cytometry. Seven days before transplantation, recipients were given infusion of recipient DCs loaded with PUVA-treated donor splenic lymphocytes (PUVA-SP DC) through the peripheral vein. The cardiac allograft survival time was evaluated by palpation every day. The frequency of CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells and their Foxp3 expression were analyzed using flow cytometry. Fourteen days after transplantation, T lymphocytes of the recipient rats receiving PUVA-SP DC were transferred to the normal LEW rats. The delayed type hypersensitivity (DTH) of the transferred LEW rats to the donor DA rats antigen then was measured. RESULTS: After co-cultured with PUVA-SP, recipient DCs still maintained an immature phenotype with low levels of MHC II, CD80 and CD86. The injection of PUVA-SP DCs significantly increased the frequencies of CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells and the expression of Foxp3 in the peripheral blood, and prolonged the allograft survival time. The donor antigen specific hyporesponsiveness could be transferred to normal LEW rats through adoptive transfusion. CONCLUSION: PUVA-SP DCs effectively up-regulate CD4(+) CD25(+) Foxp3(+) Treg and induce donor antigen specific hyporesponsiveness, thus prolonging the allograft survival time.

[Immune regulation effect of rat dendritic cells phagocytosing photochemotherapy-treated allogeneic cells on syngeneic T cells].

The aim of this study was to investigate the immune regulatory effect of dendritic cells phagocytosing photochemotherapy-treated allogeneic spleen lymphocytes on syngeneic T cells. DA rat spleen lymphocytes were treated with 8-methoxypsoralen plus UVA irradiation (PUVA). LEW rat bone marrow-derived DCs were co-cultured with PUVA-treated DA spleen lymphocytes (PUVA-SP), and the surface markers (MHC-II, CD86 and CD40) of treated DC were detected by flow cytometry. CFSE-labeled PUVA SP were incubated with LEW DCs and the phagocytosis of DCs on PUVA-SP was observed by using fluorescent microscope. The ability of DC phagocytosing allogeneic PUVA-SP (PUVA-SP DC) to stimulate the proliferation of LEW T cells was analyzed by mixed leukocyte reactions (MLR). The production of IL-4, IL-10, IL-2, IFN-gamma in MLR culture supernatant was determined by luminex method. The results indicated that the PUVA treatment effectively induced early apoptosis of DA rat spleen lymphocytes. After co-culture, DC efficiently phagocytosed allogeneic PUVA-SP and still maintained an immature phenotype with low levels of MHC II, CD40 and CD86. PUVA-SP DC induced LEW T cell hyporesponsiveness to DA rat antigen, and led to skewing of T cell cytokine expression toward Th2 (IL-10 and IL-4). It is concluded that the PUVA-SP DC effectively down-regulate T cell response to alloantigen and induce Th2 immune deviation in vitro.

Gallstone recurrence after successful percutaneous cholecystolithotomy: a 10-year follow-up of 439 cases.

BACKGROUND: Stone recurrence is a major problem in the medication of gallstones with gallbladder preservation. The aim of this study was to determine the long-term recurrence rate of gallstones and the clinical outcome after successful percutaneous cholecystolithotomy (PCCL) treatment, and to investigate the possible risk factors for gallstone recurrence. METHODS: After successful PCCL for gallstones, 439 patients were followed up during a 10-year period. The long-term gallstone recurrence rate and clinical outcome were evaluated. Risk factors associated with stone recurrence were identified. RESULTS: Gallstone recurrence was detected in 182 of 439 PCCL patients, giving an overall recurrence rate of 41.46%. The cumulative gallstone recurrence rate for each of the 10 post-operative years was 9.57%, 18.91%, 27.33%, 34.14%, 37.59%, 39.86%, 41.90%, 42.73%, 42.85%, and 43.21%, respectively. Among these recurrent patients, 94 were asymptomatic, 80 suffered from nonspecific upper gastrointestinal symptoms and 8 suffered from abdominal pain or biliary colic. Thirty-eight of the 182 patients were retreated with cholecystectomy. The risk factors for stone recurrence included a family history of gallstones, preference for fatty food, accompanying liver disease, multiple stones and poor gallbladder function pre-PCCL. CONCLUSIONS: In this study, the overall recurrence rate of gallstone was 41.46% during a 10-year period. The highest frequency of gallstone recurrence was during the 5th to 6th postoperative years and then continued to slowly increase. Risk factors for stone recurrence varied. We suggest that the use of PCCL in patients with gallstones should be considered carefully because of stone recurrence.