Surgical rationalization of living donor liver transplantation by abolition of hepatic artery reconstruction under a fixed microscope

The small diameter of the hepatic artery is one of the complexities of living donor liver transplantation (LDLT). We analyzed whether the direct suture technique using surgical loupes can simplify the operative process for LDLT compared with fixed microscopic reconstruction. We applied the direct technique to rationalize the operative process and abolished routine microsurgery from 2004. Two hundred and nine LDLT with a postoperative period over 34 months were carried out from 1996 to 2008. The patients were divided into two groups: the micro group (children: 20, adults: 72) and the non‐micro group (children: 12, adults: 97). Running anastomosis was undertaken in the non‐micro group. The anastomotic size of the children was significantly smaller than that of the adults, but larger than 2 mm (2.38 ± 0.4 vs. 2.7 ± 0.47 mm, p = 0.0005). By appropriate choice of the proximal artery, direct anastomosis is possible even in children. Early complications occurred in seven cases in the micro group, but none occurred in the non‐micro group (p < 0.05). Significant reductions were observed in operation time (p < 0.0001), blood loss (p < 0.05), and hospital stay (p < 0.01) in the non‐micro group. Non‐microscopic anastomosis is useful for the rationalization of LDLT.     

SNPs in the promoter region of the osteopontin gene as a possible host factor for sex difference in hepatocellular carcinoma development in patients with HCV

Aims

Four single nucleotide polymorphisms (SNPs) exist in the promoter region of the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and -1748 showing linkage disequilibrium to each other, and an independent SNP at nt -443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC) development was examined in patients with hepatitis C virus (HCV).

Methods

The SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC. The promoter activity was measured in HepG2 cells by the dual-luciferase reporter assay. The electrophoretic mobility shift assay was performed using nuclear extracts from the cells.

Results

Peripheral platelet counts at the time of HCC detection were greater in women with homozygous deletion at nt -155 and C/C or C/T at nt -443 than in those showing other allelic combinations, while no such difference was observed in men. The promoter activity was greater in oligonucleotides with deletions at nt -155 and C at nt -443 than in those with other haplotypes. The mobility shift assay showed double and single complexes with oligonucleotides around nt -155 and nt -443, respectively. Binding activities were greater in deletion than in G in the case of the retarded complex in the former assay and in T than in C in the latter assay. The other complex in the former assay included SRY, showing an equivalent binding activity to oligonucleotides with both alleles.

Conclusion

OPN promoter SNPs may play a role in the sexual difference in the risk of HCC development through the regulation of OPN expression in patients with HCV.     

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study

Introduction

Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients.

Methods

This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes.

Results

Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands >140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV >20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes.

Conclusions

Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient''s diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.See related commentary by Krinsley, http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot, http://ccforum.com/content/17/2/134     

Arm span–height difference is correlated with gastroesophageal reflux symptoms in aged Japanese subjects

Previous studies have indicated an association between the symptoms of gastroesophageal reflux disease (GERD) and aging plus height. In this study we investigated whether the arm span–height difference was related to GERD symptoms with a focus on aged subjects in the general population, since the arm span reflects the height in young adulthood before decreasing due to vertebral deformities from aging. A total of 285 elderly individuals (105 females) who visited nursing homes for the elderly in Japan were enrolled in this study. The GERD symptoms were evaluated by the Frequency Scale for the Symptoms of GERD (FSSG). The body weight, height and arm span were measured, and information regarding medications and complications were reviewed in each nursing record. 50.5% of women had more than 3 cm of arm span–height difference. In contrast, only 37.3% of men had more than 3 cm of arm span–height difference. The FSSG scores indicated more than 70% of subjects complained of any GERD symptoms. There was a significant correlation between the FSSG score and the arm span–height difference in the subjects with more than 3 cm of arm span-height difference (r = 0.236; p = 0.012). The correlation between the arm span–height difference and the FSSG score was significant only in women in females in the present study. In conclusion, our findings indicate that vertebral deformity evaluated by the arm span–height difference might have some positive relationship to the pathogenesis of GERD symptoms in elderly Japanese individuals.     

Impacts of probiotics on the efficacies of immune checkpoint inhibitors with or without chemotherapy for patients with advanced non-small-cell lung cancer

The relationships between the therapeutic effects of immune checkpoint inhibitors (ICIs) and the intestinal flora have attracted increasing attention. However, the effects of oral probiotics on the efficacies of ICIs used to treat non-small-cell lung cancer (NSCLC) remain unclear. We investigated the effects of probiotics on the efficacies of ICIs in patients treated with and without chemotherapy. We investigated patients with advanced NSCLC on ICI monotherapy or combination ICI and chemotherapy using the Okayama Lung Cancer Study Group Immunotherapy Database (OLCSG-ID) and the Okayama Lung Cancer Study Group Immunochemotherapy Database (OLCSG-ICD). In total, 927 patients (482 on ICI monotherapy, 445 on an ICI + chemotherapy) were enrolled. Most were male, of good performance status, smokers, and without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations. Probiotics were administered to 19% of patients on ICI monotherapies and 17% of those on ICIs + chemotherapy. Of the former patients, progression-free survival (PFS) and overall survival (OS) were significantly better in the probiotics group (PFS 7.9 vs. 2.9 months, hazard ratio [HR] 0.54, p < .001; OS not attained vs. 13.1 months, HR 0.45, p < .001). Among patients receiving ICI and chemotherapy, there were no significant differences in PFS between those on probiotics and not but OS was significantly better in the probiotics group (PFS 8.8 vs. 8.6 months, HR 0.89, p = .43; OS not attained vs. 22.6 months, HR 0.61, p = .03). Patients on probiotics experienced better outcomes following ICI treatment.     

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma

BackgroundThe primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer.MethodsIn part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM). In part 2, tremelimumab 10 mg/kg (Q4W for 6 doses followed by Q12W for 3 doses) was given in combination with durvalumab 15 mg/kg (Q4W for 13 doses) in cohort 1 (n = 4). In cohort 2 (n = 6), tremelimumab 1 mg/kg (Q4W for 4 doses) was given in combination with durvalumab 20 mg/kg (Q4W for 4 doses followed by 10 mg/kg Q2W for 22 doses), while in cohort 3 (n = 6), fixed-dose tremelimumab 75 mg Q4W for 4 doses plus durvalumab 1500 mg Q4W for 13 doses was given.ResultsIn part 1, no dose-limiting toxicities (DLTs) for tremelimumab 3 or 10 mg/kg (Q4W for 6 doses/Q12W thereafter until discontinuation) were observed. Six (75%) patients reported treatment-related adverse events (trAEs). In the MPM dose-expansion cohort, 38 (92.7%) patients reported trAEs. In part 2, one DLT (Grade 4 myasthenia gravis) was reported for tremelimumab 10 mg/kg (Q4W for 6 doses/Q12W for 3 doses) plus durvalumab 15 mg/kg (Q4W for 13 doses). One DLT (Grade 4 hyperglycemia) was reported for tremelimumab 75 mg (Q4W for 4 doses) plus durvalumab 1500 mg (Q4W for 13 doses). Fourteen (87.5%) patients reported trAEs. Tremelimumab demonstrated low immunogenicity; 1 (16.7%) patient developed antidrug antibodies.ConclusionTremelimumab 10 mg/kg (Q4W/Q12W), tremelimumab 1 mg/kg (Q4W) plus durvalumab 20 mg/kg (Q4W/10 mg/kg Q2W), and fixed-dose tremelimumab 75 mg (Q4W) plus durvalumab 1500 mg (Q4W) were safe and tolerable.ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02141347","term_id":"NCT02141347"}}NCT02141347 (https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02141347","term_id":"NCT02141347"}}NCT02141347)     

Effect of bacterium in the malignant wounds of soft tissue sarcoma

Malignant wounds (MWs) are rare skin lesions, which accompany ulceration, necrosis and infection caused by infiltration or damage by malignant tumor. The present study aimed to investigate the bacterial etiology implicated in MW in soft tissue sarcoma (STS), and the effectiveness of culture-guided perioperative antibacterial administration. A retrospective evaluation was conducted on medical records of patients who presented with MW between 2006 and 2020. A total of seven patients were included in the present study, in whom all tumors were relatively large (>5 cm) and high-grade. Subsequently, five patients underwent limb-sparing surgery, and three patients had distant metastases with a 5-year overall survival of 71%. Preoperative microbiological sampling from the wound identified 11 different bacterial strains in five patients. The infections were polymicrobial with an average of 2.6 strains isolated per patient (1 aerobic, 1.6 anaerobic bacteria). They were predominantly methicillin-sensitive Staphylococcus aureus. Patients with MWs from STS reported symptoms, including bleeding (71%), exudation (71%) and malodorous wound (43%) at the initial presentation; these completely resolved after surgery. All but one patient reported pain at the MW site with an average numeric rating scale of 4.4 at presentation that decreased to 1.4 (P=0.14) and 0.6 (P=0.04) one and two weeks after surgery, respectively. The patients had elevated C-reactive protein (71%), anemia (57%), low albumin (86%) and renal/liver dysfunction (14–29%). One patient was diagnosed with sepsis. Surgical resection afforded symptomatic relief and resolution of abnormal laboratory values. Although selected antibiotics were administered in four patients based on the preoperative antibiotic sensitivity test, surgical site infection (SSI) occurred in three patients. Therefore, the effectiveness of the selected antibiotics based on the results of the preoperative culture in preventing SSI needs to be investigated in the future. In conclusion, physicians should keep in mind that although surgical resection can improve the symptoms and abnormal values in laboratory examination form MW, it is accompanied with a high rate of SSI and poor prognosis.