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The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level ( p  < 0.0001, p  < 0.0001, p  = 0.0030, and p  = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS ( p  = 0.0003 and p  = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598–2.4586; p  < 0.0001, and HR, 1.5452; 95% CI 1.0345–2.3079; p  = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common inherited neuromuscular disease. The genetic diagnosis is not easily made because of the large size of the dystrophin gene, complex mutational spectrum and high number of tests patients undergo for diagnosis. Multiplex ligation-dependent probe amplification (MLPA) has been used as the initial diagnostic test of choice. Although MLPA can diagnose 70% of DMD/BMD patients having deletions/duplications, the remaining 30% of patients with small mutations require further analysis, such as Sanger sequencing. We applied a high-throughput method using Ion Torrent next-generation sequencing technology and diagnosed 92% of patients with DMD/BMD in a single analysis. We designed a multiplex primer pool for DMD and sequenced 67 cases having different mutations: 37 with deletions/duplications and 30 with small mutations or short insertions/deletions in DMD, using an Ion PGM sequencer. The results were compared with those from MLPA or Sanger sequencing. All deletions were detected. In contrast, 50% of duplications were correctly identified compared with the MLPA method. Small insertions in consecutive bases could not be detected. We estimated that Ion Torrent sequencing could diagnose ~92% of DMD/BMD patients according to the mutational spectrum of our cohort. Our results clearly indicate that this method is suitable for routine clinical practice providing novel insights into comprehensive genetic information for future molecular therapy.

Background/Aim: We investigated the anti-proliferative effect of quercetin on liver cancer cell lines. Materials and Methods: Thirteen liver cancer cell lines were cultured followed by treatment with varying concentrations of quercetin (0-100 μM) or quercetin and 5-FU, and the cell viability was analysed by the MTT assay. Flow cytometry was also used to examine cell cycle progression after treatment with quercetin. Results: The addition of quercetin resulted in a dose- and time-dependent suppression of cell proliferation. In some cell lines, treatment with quercetin and 5-FU caused an additional or synergistic effect. Most cell lines displayed cell cycle arrest at different phases of the cell cycle. Conclusion: Quercetin inhibits the proliferation of liver cancer cells via induction of apoptosis and cell cycle arrest.

Background/Aim: Recent studies have demonstrated the efficacy of salvage surgery following downstaging of hepatocellular carcinoma (HCC). The aim was to assess the outcomes of salvage surgery after successful downstaging using hepatic arterial infusion chemotherapy (HAIC). Patients and Methods: Patients whose diagnosis was unresectable locally advanced HCC and who were resected after conversion to a resectable status by HAIC were included. The overall survival (OS) rate, and disease-free survival (DFS) rate were analyzed by stratifying patients into those with Vp3/4, Vv2/3, and those without major vascular invasion (MVI). Results: Eighteen patients were censored. Among them, six patients had Vp3/4, four patients had Vv2/3, and eight patients had no MVI. The 5-year OS rates of patients with Vp3/4 and those without MVI were 83% and 73%, respectively, whereas those with Vv2/3 had 0% (p<0.001). Conclusion: Salvage surgery has the potential to provide excellent outcomes in resectable HCC patients, except for those with Vv2/3.

Background/Aim: Surgical resection is the standard treatment for bile duct cancer. However, even when surgical resection is possible, the 5-year survival rate is reportedly 25.0-55.0%. Therefore, bile duct cancer is associated with poor prognoses. We conducted a clinicopathological investigation, focusing on the histological phenomenon of tumour budding, which has previously been reported to be correlated with the survival of patients with a variety of cancers. Patients and Methods: To investigate the significance of tumour budding in distal bile duct cancer, we recruited 65 patients who underwent pancreatoduodenectomy at our institution between 1995 and 2011. Tumour budding was observed and evaluated using the ‘hot spot method’. The ‘low’ budding group comprised 0-4 cell clusters and the ‘high’ budding group ≥5 cell clusters. Additionally, immunostaining was performed in high-budding areas. Results: Tumour budding and stage were confirmed using a Cox proportional hazards model as independent prognostic factors for overall survival (p<0.05) in all patients. There was a significant association between budding and zinc finger E-box binding homeobox 1 expression, an endothelial-mesenchymal transition-induced transcription factor. In stage II cases, the prognosis was significantly worse in the ‘high’ budding group compared to that in the ‘low’ budding group. Conclusion: The budding phenomenon is an independent prognostic factor for patients with distal bile duct cancer. Understanding the mechanisms underlying tumour budding in distal bile duct cancer and its relationship with poor prognoses may be useful for the development of novel treatments for this disease.

Comprehensive genome analysis may reveal secondary findings (SFs) including pathogenic variants of genes other than those originally targeted. Comprehensive genetic analysis of rare diseases is generally performed as research in Japan. Therefore, the status and difficulties in SF disclosure remain unclear. To obtain information for the appropriate disclosure of SFs in rare diseases, we conducted a survey on how SFs are handled in clinical practice by facilities that outsource comprehensive genetic testing to other facilities. The response rate was 66.7% (40/60). Among the responding facilities, 55% had a policy of disclosing SFs with clinical utility and considered targeting actionable SFs with high penetrance. These facilities had difficulties in determining the disclosure targets (51%) and in genetic counseling (38%). Improving genetic literacy, establishment of surveillance systems, and providing insurance coverage for medical care to unaffected carriers were commonly cited as solutions to these difficulties. A comparison of the willingness to disclose SFs between overseas and in Japan showed more reluctance in Japan (86% vs. 65% for actionable SFs and 62% vs. 16% for non-actionable SFs). The group with difficulty in determining disclosure targets was significantly more likely to discuss this at conferences with other facilities and to refer guidelines. This suggests that the group with difficulties was unable to make decisions solely at their own facility and sought collaboration with other facilities. These findings suggest the necessity for a system that allows consultation with experts across facilities and guidelines that set forth policies for determining SFs.

Background It is unclear whether hepatectomy, which ranges in invasiveness from partial to major hepatectomy, is safe and feasible for older adult patients. Therefore, we compared its postoperative complications and long-term outcomes between younger and older adult patients. Methods Patients who underwent hepatectomies for hepatocellular carcinoma ( N  = 883) were evaluated. Patients were divided into two groups: aged < 75 years ( N  = 593) and ≥ 75 years ( N  = 290). Short-term outcomes and prognoses were compared between the groups in the entire cohort. The same analyses were performed for the major hepatectomy cohort. Results In the entire cohort, no significant differences were found in complications between patients aged < 75 and ≥ 75 years, and the multivariate analysis did not reveal age as a prognostic factor for postoperative complications. However, overall survival was significantly worse in older patients, although no significant differences were noted in time to recurrence or cancer-specific survival. In the multivariate analyses of time to recurrence, overall survival, and cancer-specific survival, although older age was an independent poor prognostic factor for overall survival, it was not a prognostic factor for time to recurrence and cancer-specific survival. In the major hepatectomy subgroup, short- and long-term outcomes, including time to recurrence, overall survival, and cancer-specific survival, did not differ significantly between the age groups. In the multivariate analysis, age was not a significant prognostic factor for complications, time to recurrence, overall survival, or cancer-specific survival. Conclusion Hepatectomy, including minor and major hepatectomy, may be safe and oncologically feasible options for selected older adult patients with hepatocellular carcinoma.

Background Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1 , DNMT3B , or LRIF1 . Genetic diagnosis of FSHD is challenging because of the complex procedures required. Methods We applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients. Results We found significant hypomethylation of contracted 4q-D4Z4 repeats in FSHD1, and both 4q- and 10q-D4Z4 repeats in FSHD2. We also found that the hypomethylation in the contracted D4Z4 in FSHD1 is moderately correlated with patient phenotypes. Conclusions Our method contributes to the development for the diagnosis of FSHD using Nanopore long-read sequencing. This finding might give insight into the mechanisms by which repeat contraction causes disease pathogenesis.

Numb chin syndrome (NCS) is hypesthesia of the mandible and lower lip caused by damage to the inferior alveolar or mandibular nerves, commonly due to dental treatment or osteomyelitis, but occasionally caused by malignant tumors. We report the case of a male in his 60s. He came to our hospital with a chief complaint of mandibular pain and paresthesia in the right side of the mental region. He had noticed swelling of the left mandible one month before the initial visit and strong hypesthesia of the right side of the mental region one week before the initial visit. Panoramic radiographs showed slight osteosclerosis of the left side mandible at the initial visit. Blood tests showed only a slight inflammatory reaction. The diagnosis of mandibular osteomyelitis and numb chin syndrome was made, and a contrast-enhanced CT scan was performed to investigate the possibility of neoplastic lesions, but no obvious cause was found. Osteosclerosis was minimal. A tissue biopsy was recommended, but the patient did not consent. Considering the possibility of NCS due to a hematologic disorder, the patient was referred to a hematologist, but no cause could be identified at the initial visit. With time, the markedly severe pain worsened, and the possibility of a neoplastic lesion was again suspected. Blood tests were performed, which revealed abnormally high levels of CA19 and CEA. He consulted a gastroenterologist, who found a tumor in the ileocecal region on contrast-enhanced CT, and multiple systemic metastases were found on a PET-CT scan the next day. Systemic chemotherapy was administered for multiple metastatic unresectable colorectal cancer (cT4N1aMc2 stage IVc).

Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phospho-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis.