Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Background and Aims

Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies.

Methods

We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI).

Results

Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy.

Conclusions

ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.     

Effects of intraoperative blood loss during liver resection on patients’ outcome: a single-center experience

Background/aim Operative bleeding is one of the major determinants of outcome in liver surgery. This study aimed to describe the impact of intraoperative blood loss on the postoperative course of liver resection (LR). Materials and methods The data of 257 patients who were treated with LR between January 2007 and October 2018 were retrospectively analyzed. LRs were performed via intermittent portal triad clamping (PTC) under low central venous pressure. Results LRs were performed for 67.7% of patients with a malignant disease and 32.3% of patients with a benign disease. Major LR was performed in 89 patients (34.6%). The mean PTC period was 20.32 min (±13.7). The median intraoperative bleeding amount was 200 mL (5–3500 mL), the 30-day mortality rate was 4.3%, and the morbidity rate was 31.9%. The hospital stay (p = 0.002), morbidity (p = 0.009), and 30-day mortality (p = 0.041) of patients with a bleeding amount of more than 500 mL significantly increased. Conclusion Surgeons should consider the adverse effects of intraoperative bleeding during liver resection on patients’ outcome. Favorable outcomes would be obtained with diligent postoperative care.     

Gradual detorsion of torsioned rat testis attenuates ischemia reperfusion injury

Aim

This study was designed to investigate effect of gradual detorsion on testicular ischemia reperfusion injury.

Materials and Methods

A total of 21 male rats were divided into 3 groups, each containing 7 rats. Torsion was created by rotating the left testis 720° in a clockwise direction. Group 1 underwent sham operation. Group 2 (sudden detorsion) served as a torsion/detorsion group, receiving 2 hours torsion and 2 hours detorsion. In group 3, 360° detorsion was done for 20 minutes after 720° torsion for 2 hours. Then, testis was done full detorsion for 100 minutes. At the end of the experiments (fourth hour), left orchiectomy was performed to measure the tissue levels of malondialdehyde (MDA), superoxide dismutase, and glutathione peroxidase and to perform histologic examination in testes.

Results

The MDA levels of testis tissues were significantly increased in the sudden detorsion group as compared with the sham group. We found decrease of the MDA level in gradual detorsion group, but it was not a statistically significant amount. Significant decrease was found in the superoxide dismutase and glutathione peroxidase activities in the sudden detorsion group as compared with the sham and gradual detorsion groups. Histologic examinations were in accordance with the testicular tissue MDA levels.

Conclusion

In the light of our biochemical and histopathologic findings, we can say that gradual detorsion has a trend to decrease the degree of testicular reperfusion injury in the rat torsion/detorsion model.     

Human papillomavirus in tonsillectomy specimen from China and Pakistan — Prevalence and genotype distribution

Background

The expected corresponding increase in tonsillar human papillomavirus (HPV) infection associated with increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) substantiate the evaluation of normal tonsillar tissue in different population. The epidemiology of HPV in tonsillar tissue varies geographically. This study evaluated samples from two countries to determine the prevalence in respective samples.

Characterization and Antibiotic Sensitivity Profile of Bacteria in Orofacial Abscesses of Odontogenic Origin

Background

Odontogenic infections range from peripheral abscess to superficial and deep infections leading to severe infections in head and neck region. This study was aimed to assess bacterial isolates responsible for orofacial infection of odontogenic origin and their drug susceptibility patterns so as to provide better perceptive for the management of odontogenic infections.

Methods

The study was made in a selected cohort of patients, irrespective of age and gender having moderate and severe orofacial infections of odontogenic origin admitted to Yenepoya University Hospital. Pus samples were collected and identification of bacteria was performed by 16S rRNA gene sequencing. Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method.

Result

A total of 37 study subjects were included, with bacterial isolation rate of 31 (83.7 %). The mean age presented of all patients was 40.62. Of all, 24 (64.9 %) were males. Staphylococcus aureus, Enterobacter claocae subsp. dissolvens, Klebsiella quasipneumoniae subsp. similipneumoniae, Staphylococcus aureus subsp. anaerobius and Klebsiella pneumoniae subsp. ozaenae were the most prevalent isolates. Result showed that 58.6 % of the isolates were resistant to gentamicin, 52.5 % for ampicillin, 51.3 % for piperacillin; least resistant being 18.9 % for azithromycin.

Conclusion

High prevalence of bacterial isolates was found, Staphylococcus aureus being the dominant. Most of the bacteria were resistant to different classes of antibiotics. Appropriate antibiotics should be given based on the bacterial isolates, culture sensitivity and clinical course of the disease.