Extracellular water to total body water ratio may mediate the association between phase angle and mortality in patients with cancer cachexia: A single-center, retrospective study.

BACKGROUND & AIMS: Recently, prognostic factors for cancer cachexia patients have been reported. We hypothesized that phase angle (PhA), which is measured by bioelectrical impedance analysis (BIA), might be a promising marker for assessing the nutritional status and prognosis of cancer patients. This study aimed to evaluate the predictive utility of PhA, which is mediated by several BIA factors and other anthropometric parameters, such as calf circumference, for the prognosis of cancer cachexia patients. METHODS: Consecutive patients (114, both outpatients and inpatients) with an unselected stage of cancer cachexia were recruited between July 2018 and December 2019 in Fujita Health University Hospital for this retrospective cohort study. Their mean age was 74.0 years (standard deviation, 8.5); among the total, 70 were men and 44 women. A time-dependent Cox proportional-hazards regression analysis (adjusted for age and sex) was performed to assess the following: 1) the association between potential mediators and mortality; 2) the association between five PhAs and statistically significant mediators from 1); and 3) the association between the five PhAs and mortality. Finally, Kaplan-Meier survival curves were constructed and compared between the two groups based on the patients' median baseline ratio of extracellular water (ECW) to total body water (TBW) using a log-rank test. RESULTS: The ECW/TBW ratio (hazard ratio [HR] per 1-interquartile range [IQR] increase: 2.87; 95% confidence interval [CI]: 1.46, 5.46; p < 0.001) and skeletal muscle mass index (HR per 1-IQR increase: 0.67; 95% CI: 0.51, 0.89; p = 0.001) were associated with mortality. All five PhAs were associated with the ECW/TBW ratio (p < 0.001). Before adjustment for the ECW/TBW ratio, all five PhAs were associated with mortality (p < 0.001); only the association of the PhAs of the left arm and the trunk retained the statistical significance after adjusting for confounders (p < 0.05). The median survival times in the low (370 days; 95% CI: 168, not calculated) and high ECW/TBW groups (101 days; 95% CI: 61, 219) differed significantly (p < 0.001). CONCLUSIONS: The association between PhA and mortality in cancer cachexia patients was largely mediated by the ECW/TBW ratio. We believe that adjusting PhA for the ECW/TBW ratio may improve the prognostication of cancer patients with cachexia, ultimately improving their palliative care.

Multicentric prospective study of effect of dietary intake on quality of life for patients with end-stage cancers.

OBJECTIVE: Impaired dietary intake (DI) contributes to deterioration of quality of life (QOL) in patients with end-stage diseases, including cancer, but the effects of DI on QOL specifically in terminal cancer has not been widely studied. Here, we evaluated the relationship between DI and QOL in patients with end-stage cancers. METHODS: We evaluated the energy amount of DI, performance status (PS) and QLQ-C15-PAL score of cancer patients with short prognoses in multicentre survey and analysed the parameters that influence QOL. RESULTS: We recruited 33 patients in this study. In univariate analysis, DI was significantly associated with PS (P=0.002, r=-0.531), physical functioning (P=0.003, r=-0.503), fatigue (P=0.038, r=-0.362), and appetite loss (P=0.004, r=-0.490). CONCLUSIONS: Improved DI could contribute to QOL of patients with end-stage cancers.

Preventing pancreatic fistula after distal pancreatectomy: An invagination method.

Following an increase in the use of the GIA stapler for treating a pancreatic stump, more techniques to prevent postoperative pancreatic juice leakage have been required. We describe one successful case using our new technique of invaginating the cut end of the pancreas into the stomach to prevent a pancreatic fistula (PF) from occurring. A 50-year-old woman with pancreatic cancer in the tail of the pancreas underwent distal pancreatectomy, causing a grade A PF. We resected the distal pancreas without additional reinforcement to invaginate the stump into the gastric posterior wall with single layer anastomosis using a 3-0 absorbable suture. The drain tubes were removed on the third postoperative day. Although a grade A PF was noted, the patient was discharged on foot on the eleventh postoperative day. Our technique may be a suitable method for patients with a pancreatic body and tail tumor.

Efficacy of transversus abdominis plane block and rectus sheath block in laparoscopic inguinal hernia surgery.

We aimed to assess the efficacy of transversus abdominis plane (TAP) block and rectus sheath (RS) block in patients undergoing laparoscopic inguinal hernia surgery. Few studies have addressed the efficacy and safety associated with TAP block and RS block for laparoscopic surgery. Thirty-two patients underwent laparoscopic inguinal hernia surgery, either with TAP and RS block (Block(+) group, n = 18) or without peripheral nerve block (Block(-) group, n = 14). Preoperatively, TAP and RS block were performed through ultrasound guidance. We evaluated postoperative pain control and patient outcomes. The mean postoperative hospital stays were 1.56 days (Block+ group) and 2.07 days (Block(-) group; range, 1-3 days in both groups; P = 0.0038). A total of 11 patients and 1 patient underwent day surgery in the Block(+) and Block(-) groups, respectively (P = 0.0012). Good postoperative pain control was more commonly observed in the Block(+) group than in the Block(-) group (P = 0.011). TAP and RS block was effective in reducing postoperative pain and was associated with a fast recovery in patients undergoing laparoscopic inguinal hernia surgery.

Hepatic organoid formation in collagen sponge of cells isolated from human liver tissues.

We examined whether small hepatocytes (SHs), which are hepatic progenitor cells, could be isolated from a normal human liver and whether human hepatic cells could form hepatic organoids in a collagen sponge. Normal liver tissues were obtained from resected specimens from nine patients who underwent hepatic resection. Isolated hepatic cells were plated on dishes and a collagen sponge. More than 1 month later, SH-like cells appeared and proliferated on the dishes, whereas cell aggregates were formed in the sponge and showed characteristic tissue architecture: columnar and/or cuboidal epithelial cells lined the surface of the sponge. Clusters of epithelial cells with a large cytoplasm and ductular structures were observed under the lining cells. The lining and ductular cells were positive for cytokeratins 7 and 19, which indicated they were biliary epithelial cells (BECs), and the epithelial cells forming clusters were positive for the anti-human hepatocyte antibody, identifying them as hepatocytes. Some lining cells were positive for both the hepatic marker and the BEC markers. The cells in the collagen sponge actively proliferated and the hepatocytes excreted albumin into the medium. Thus, hepatic organoids could be reconstructed in a collagen sponge by normal human liver cells.

Absence of PERV infection in baboons after transgenic porcine liver perfusion.

BACKGROUND: Xenotransplantation offers great promise to supplement the shortage of human organs available for transplant, but cross-species infection is a substantial concern. Porcine endogenous retrovirus (PERV), in particular, is thought to pose a risk as a potential pathogen to humans. We evaluated whether PERV is capable of infecting nonhuman primates in vivo after extracorporeal porcine liver perfusion (ECLP). METHODS: Livers were harvested from six human decay-accelerating factor (h-DAF) transgenic piglets and perfused with fresh baboon blood via the portal vein and the hepatic artery. Six healthy baboons underwent direct cross-circulation with the ECLP for 13 to 24 h without immunosuppression. Peripheral blood and bone marrow of baboons were sampled periodically until the baboons were euthanized for the examination of various organ tissue samples. Genomic DNA was extracted from those samples and tested for PERV and pig-specific centromeric DNA sequences by quantitative PCR. Validation showed that the assay could detect one copy of PERV in a background of 150,000 baboon cells, and it was quantitative over a range from 10 to 10(6) copies of PERV. RESULTS: PERV sequences were detected in a high number (4.4 x 10(3)-1.6 x 10(4)/1 microg) in peripheral leukocyte DNA during the initial phases of ECLP, but they disappeared within 1 week. Bone marrow DNA contained PERV sequences longer than peripheral blood, but PERV signals became negative within 1 month. No PERV DNA relapse was seen over the course of this study. Pig-specific centromeric sequences were also detected in the same manner. At 6 months or 1 year after ECLP, no PERV or pig-specific centromeric sequences were detected in the genomic DNA obtained from the following organs: skin, lymph nodes, spleen, liver, pancreas, kidney, heart, and lung. CONCLUSIONS: ECLP did not result in PERV infection or pig-cell microchimerism in baboons.

Bioartificial liver with whole blood perfusion.

In our series of studies, we have made an effort to develop a bioartificial liver (BAL) system through which whole blood can be perfused as in hemodialysis therapy. In this study, BAL cartridges containing porcine hepatocytes were prepared and perfused in an extracapillary space with human whole blood in vitro. Lidocaine loading tests were performed to evaluate the detoxification ability of the BAL. The clearance value of lidocaine decreased during the initial 6 hours to about 50% of the initial value. After that, it was almost stable until 48 hours. After 48 hours perfusion, thin sections of the hollow fibers containing hepatocytes were prepared and stained with hematoxylin-eosin and immunohistochemically stained for membrane attack complex (MAC). The porcine hepatocytes formed aggregates in the hollow fibers, nuclei in the cells were observed clearly, and MAC was not seen on the porcine hepatocyte aggregation. A hollow fiber that can reject 90% of molecules with molecular weight of 50 kDa effectively protects porcine hepatocytes from humoral immunity. The in vivo assessment of the BAL cartridge was performed using a canine model for 24 hours. No significant hemolysis or thrombus that affected the BAL system and the canine were observed. These results suggest that our BAL system is a promising liver assist device through which patients' whole blood can be perfused.

Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates.

BACKGROUND: We developed an extracorporeal liver perfusion (ECLP) system as a liver-assist device. In this study, we evaluated the safety of the ECLP using human decay accelerating factor (hDAF) transgenic porcine livers in healthy baboons. METHODS: Livers were isolated from five hDAF transgenic pigs and five nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and healthy baboons were performed without immunosuppressive agents. Cross-circulation was discontinued in any of the following circumstances: elevated hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24-hr well-conditioned cross-circulation. RESULTS: The cross-circulations with nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three cross-circulations with hDAF transgenic porcine livers were performed for 24 hr; the other two cross-circulations were discontinued at 13 and 17 hr because of massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1 hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver was less than that in the nontransgenic liver, although immunoglobulin-M deposition was comparable. The porcine livers showed no apparent interlobular bleeding or lobular necrosis. All porcine livers maintained bile production during the cross-circulation. No baboons showed any serious complications after the cross-circulation. CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.

Long-term culture of primary human hepatocytes with preservation of proliferative capacity and differentiated functions.

BACKGROUND: The aim of this study was to develop a suitable method for the prolonged culture and maintenance of human hepatocytes with preservation of both proliferative capacity and differentiated functions. MATERIALS AND METHODS: Primary human hepatocytes were isolated from small pieces of liver tissue obtained from 15 patients who underwent hepatic resection. Hepatocytes were cultured in keratinocyte-stimulating factor medium supplemented with 10% human serum, 10 mM nicotinamide, 10 ng/ml epidermal growth factor, 0.5 microg/ml insulin, 10(-7) M dexamethasone, and antibiotics. Hepatic differentiation and function were analyzed by immunocytochemistry, Western blot, ELISA, lidocaine metabolism, and urea synthesis. Ultrastructural analysis of cultured hepatocytes was performed by electron microscopy. RESULTS: Many primary hepatocytes were maintained for more than 56 days. Hepatocytes proliferated during the initial 14 days, and bromodeoxyuridine labeling indices were 15.2, 12.2, and 6.2% at days 5, 10, and 15, respectively. Electron micrographs of the hepatocytes at day 28 demonstrated numerous mitochondria, rough endoplasmic reticulum, large peroxisomes, and glycogen granules. Albumin secretion increased for the first 14 days and then gradually decreased thereafter but was maintained at levels greater than 2 microg/ml/h until day 56. alpha(1)-Antitrypsin, alpha(1)-antichymotrypsin, and ceruloplasmin production was also observed at day 56, while lidocaine metabolism and urea synthesis were maintained for a long time. CONCLUSION: This hepatocyte culture method facilitates the prolonged culture of primary human hepatocytes with preservation of hepatocyte differentiation, function, and proliferative capacity.