Changes in mandibular position during midface distraction in patients with syndromic craniosynostosis.

The purpose of this study was to evaluate changes in mandibular position during midface distraction. Midface distraction was performed in patients with syndromic craniosynostosis to increase upper airway volume. Although this treatment resulted in changes in occlusion, the concomitant changes in mandibular position were poorly understood. In this retrospective study, three-dimensional (3D) cephalograms were obtained before and after midface distraction in 15 patients with syndromic craniosynostosis. Perioperative polysomnography scores and changes in maxillary and mandibular position, mandibular volume, and upper airway volume were analyzed. Results showed a significant improvement in apnea-hypopnea index (AHI) (from 20.6 ± 21.3 to 6.9 ± 5.1, p < 0.05) and upper airway volume (from 2951.65 ± 2286.38 to 5218.04 ± 3150.05 mm3, p < 0.001). When the lowest point of the sella turcica was set as the reference point, the mandible moved significantly in an anterior direction (from 47.9 ± 11.5 to 51.9 ± 9.8 mm, p < 0.05). Mandibular volume did not change significantly perioperatively (from 32530.19 ± 10726.01 to 35590.50 ± 14879.21 mm3, p = 0.10). There were positive correlations between the rates of improvement in AHI and the amount of mandibular movement in the anterior and inferior directions (both p < 0.05). Within the limitations of the study, it seems that the mandible moved in the anterior-inferior direction after midface distraction, and the amount of movement correlated with improvement in respiratory function. Therefore, it is important to consider the position of the mandible when determining the direction of midface distraction, as it may influence the therapeutic effect.

On-shelf circulation of warm water toward the Totten Ice Shelf in East Antarctica.

The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features. Access of warm water to the Totten Ice Shelf (TIS) cavity is facilitated by a deep shelf break, a broad and deep depression on the shelf, a cyclonic circulation that carries warm water to the inner shelf, and deep troughs that provide direct access to the TIS cavity. The temperature of the warmest water reaching the TIS cavity varies by ~0.8 °C on an interannual timescale. Numerical simulations constrained by the updated bathymetry demonstrate that the deep troughs play a critical role in regulating ocean heat transport to the TIS cavity and the subsequent basal melt of the ice shelf.

Initial drainage-related prognostic factors for perihilar cholangiocarcinoma: A single-center retrospective study.

Objectives: Perihilar cholangiocarcinoma (PCC) is a complex disorder involving the hepatic hilum. Multiple endoscopic retrograde cholangiopancreatography sessions are necessary for diagnosis and treatment with underlying cholangitis risk. Our aim is to clarify the initial-drainage-related prognostic factors of PCC. Methods: This study was a single-center retrospective study. A total of 104 consecutive patients diagnosed with PCC from January 2010 to February 2020 were enrolled. We defined the diagnostic period as the time between the first biliary drainage attempt and the final drainage when treatment, including surgery or chemotherapy, was started. We focused on this initial period and analyzed the endoscopy-related factors that affected mortality. Results: Overall survival of all PCC patients was 599 days. Overall survival of surgically treated patients and unresectable patients were 893 days and 512 days, respectively. In 48 surgically treated patients, drainage-related cholangitis within the diagnostic period, defined as new cholangitis that occurred after the first biliary drainage attempt, worsened overall survival from 1460 days to 607 days. Endoscopic sphincterotomy, the first drainage method other than endoscopic nasobiliary drainage, and four or more endoscopic retrograde cholangiopancreatography sessions were risk factors for drainage-related cholangitis. Drainage-related cholangitis increased pathological lymph node metastasis. Percutaneous transhepatic biliary drainage as final drainage was the only prognostic factor in unresectable chemotherapy-treated patients. Conclusions: Drainage-related cholangitis worsened the prognosis in PCC patients who underwent surgery. Appropriate endoscopic retrograde cholangiopancreatography strategies, especially during the diagnostic period, are of great importance in PCC.

Dominant frazil ice production in the Cape Darnley polynya leading to Antarctic Bottom Water formation.

Antarctic Bottom Water (AABW) occupies the abyssal layer of the world ocean and contributes to the global overturning circulation. It originates from dense shelf water, which forms from brine rejection during sea ice production. An important region of AABW formation has been identified off the Cape Darnley polynya. However, it remains unclear why and how high ice production leads to AABW formation. Using moored acoustic measurements and a satellite microwave algorithm, we reveal that underwater frazil ice dominates in the polynya. This underwater ice formation prevents heat-insulating surface-cover ice forming, thereby enabling efficient ice production. The high ice production in the nearshore and longer residence times create high-salinity source water for the AABW. Underwater frazil ice occurs as long as strong winds continue and occasionally penetrates depths of at least 80 m. Deep-penetrating frazil ice is particularly prominent in this polynya, while it also occurs in other Antarctic coastal polynyas.

Intravenous ferric derisomaltose for iron-deficiency anemia associated with gastrointestinal diseases: a single-arm, randomized, uncontrolled, open-label study.

Iron-deficiency anemia (IDA) associated with gastrointestinal diseases is the second most common etiology of IDA in Japan, and is most often caused by gastrointestinal bleeding. A multicenter, single-arm (2 groups), open-label, phase III study was conducted to assess the efficacy and safety of ferric derisomaltose (FDI) when administered by intravenous (IV) bolus injection (n = 30) or drip infusion (n = 10) in Japanese patients with IDA associated with gastrointestinal diseases. The primary endpoint, which was the mean maximum change in hemoglobin (Hb) concentration from baseline, was 4.33 (95% confidence interval, 3.82-4.83) g/dL in the overall population (4.27 [3.83-4.71] g/dL in the bolus injection group and 4.49 [2.69-6.29] g/dL in the drip infusion group). Treatment-emergent adverse events (TEAEs) were reported in 24 patients (60.0%) in the overall population (18 patients [60.0%] in the bolus injection group and 6 patients [60.0%] in the drip infusion group). No serious treatment-related TEAEs or unexpected safety findings were reported during the study. These findings reveal a favorable efficacy and safety profile for FDI when administered by IV bolus injection or drip infusion in Japanese patients with IDA associated with gastrointestinal diseases.

Intravenous ferric derisomaltose versus saccharated ferric oxide for iron deficiency anemia associated with menorrhagia: a randomized, open-label, active-controlled, noninferiority study.

A multicenter, randomized, open-label, phase III study was conducted to compare the efficacy and safety of intravenous ferric derisomaltose (FDI) versus saccharated ferric oxide (SFO) in Japanese patients with iron deficiency anemia associated with menorrhagia. FDI can be administered as a single dose up to 1000 mg, whereas SFO has a maximum single dose of 120 mg. The primary endpoint, which was the maximum change in hemoglobin concentration from baseline, was noninferior for the FDI group compared with the SFO group. The incidence of treatment-emergent adverse events was lower in the FDI group (66.2%) than in the SFO group (90.8%). Notably, the incidence of serum phosphorus level < 2.0 mg/dL was significantly lower in the FDI group (8.4%) than in the SFO group (83.2%), and severe hypophosphatemia (≤ 1.0 mg/dL) occurred in 6.7% of SFO­treated patients compared with none in the FDI group. The percentage of patients who achieved the cumulative total iron dose during the 8-week treatment period was higher in the FDI group (92.8%) than in the SFO group (43.2%). The study met its primary endpoint, and also demonstrated the tolerability of a high dose of FDI per infusion, with a lower incidence of hypophosphatemia.

The COVID-19 Pandemic and Families in Japan.

This paper, which is authored by members of the Japanese Association of Family Therapy (JAFT), describes the COVID-19 pandemic in Japan from a family systems perspective. The authors are active members of JAFT and include current and past presidents and officers. We describe the course of the pandemic and the ways in which government policies to mitigate the pandemic have affected Japanese families. Challenges that affect Japanese families include the inability to participate in family and social rituals, prescribed gender roles that specifically affect women, high suicide rates, and prejudice against those who are at risk of spreading the infection. The need to shelter in place has also forced family homes to function as a workplace for parents, classrooms for children, and day care services for frail elders, which has resulted in psychological distress among individuals and conflicts among families. We discuss ways that therapists have worked with Japanese families using online therapy.

Dysregulation of PI3K and Hippo signaling pathways synergistically induces chronic pancreatitis via CTGF upregulation.

The role of PI3K and Hippo signaling in chronic pancreatitis (CP) pathogenesis is unclear. Therefore, we assessed the involvement of these pathways in CP by examining the PI3K and Hippo signaling components PTEN and SAV1, respectively. We observed significant decreases in pancreatic PTEN and SAV1 levels in 2 murine CP models: repeated cerulein injection and pancreatic ductal ligation. Additionally, pancreas-specific deletion of Pten and Sav1 (DKO) induced CP in mice. Pancreatic connective tissue growth factor (CTGF) was markedly upregulated in both CP models and DKO mice, and pancreatic CCAAT/enhancer-binding protein-α (CEBPA) expression was downregulated in the CP models. Interestingly, in pancreatic acinar cells (PACs), CEBPA knockdown reduced PTEN and SAV1 and increased CTGF levels in vitro. Furthermore, CEBPA knockdown in PACs induced acinar-to-ductal metaplasia and activation of cocultured macrophages and pancreatic stellate cells. These results were mitigated by CTGF inhibition. CP in DKO mice was also ameliorated by Ctgf gene deletion, and cerulein-induced CP was alleviated by antibody-mediated CTGF neutralization. Finally, we observed significantly decreased PTEN, SAV1, and CEBPA and increased CTGF levels in human CP tissues compared with nonpancreatitis tissues. Taken together, our results indicate that dysregulation of PI3K and Hippo signaling induces CP via CTGF upregulation.

Strong ice-ocean interaction beneath Shirase Glacier Tongue in East Antarctica.

Mass loss from the Antarctic ice sheet, Earth's largest freshwater reservoir, results directly in global sea-level rise and Southern Ocean freshening. Observational and modeling studies have demonstrated that ice shelf basal melting, resulting from the inflow of warm water onto the Antarctic continental shelf, plays a key role in the ice sheet's mass balance. In recent decades, warm ocean-cryosphere interaction in the Amundsen and Bellingshausen seas has received a great deal of attention. However, except for Totten Ice Shelf, East Antarctic ice shelves typically have cold ice cavities with low basal melt rates. Here we present direct observational evidence of high basal melt rates (7-16 m yr-1) beneath an East Antarctic ice shelf, Shirase Glacier Tongue, driven by southward-flowing warm water guided by a deep continuous trough extending to the continental slope. The strength of the alongshore wind controls the thickness of the inflowing warm water layer and the rate of basal melting.

Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels.

Diabetes mellitus is a well-known risk factor for pancreatic cancer. We focused on hyperglycemia, a main feature of diabetes mellitus, and uncovered its effect on precancerous pancreatic intraepithelial neoplasia (PanIN) progression. In vivo induction of hyperglycemia with 100 mg/kg streptozotocin in KrasLSL G12D Pdx1Cre (KP) mice promoted the PanIN formation and progression. Preconditioning with a high- or low-glucose medium for 28 days showed that a high-glucose environment increased cell viability and sphere formation in PANC-1, a Kras-mutant human pancreatic ductal adenocarcinoma cell line, and mPKC1, a Kras-mutant murine pancreatic cancer cell line. In contrast, no changes were observed in BxPC3, a Kras-wild-type human pancreatic cancer cell line. Orthotopic injection of mPKC1 into the pancreatic tails of BL6/J mice showed that cells maintained in high-glucose medium grew into larger tumors than did those maintained in low-glucose medium. Hyperglycemia strengthened the STAT3 phosphorylation, which was accompanied by elevated MYC expression in Kras-mutant cells. Immunohistochemistry showed stronger phosphorylated STAT3 (pSTAT3) and MYC staining in PanINs from diabetic KP mice than in those from euglycemic counterparts. STAT3 inhibition with 1 µM STAT3 inhibitor STATTIC in Kras-mutant pancreatic cell lines blocked the cell viability- and sphere formation-enhancing effects of the hyperglycemic environment and reversed the elevated pSTAT3 and MYC expression. MYC knockdown did not affect cell viability but did reduce sphere formation. No decrease in pSTAT3 expression was observed upon siMYC treatment. In conclusion, hyperglycemia, on a Kras-mutant background, aggravates the PanIN progression, which is accompanied by elevated pSTAT3 and MYC expression.

Risk Factors for Pancreatic Cancer and the Necessity of Long-Term Surveillance in Patients With Pancreatic Cystic Lesions.

OBJECTIVES: Pancreatic cystic lesions (PCLs) are a risk factor for pancreatic cancer (PC). Which PCLs should be surveilled and necessity of long-term observation are still controversial. METHODS: From January 2000 to March 2016, we enrolled 1137 patients with PCLs observed for 1 year. We defined PCLs with cyst size of greater than 30 mm, main pancreatic duct (MPD) of greater than 5 mm or mural nodule as high-risk group, and others as low-risk group (LRG). Kaplan-Meier method and Cox proportional hazard model were applied to assess incidence and risk factors of PC. RESULTS: In 107 high-risk group and 1030 LRG patients, mean observation period was 4.3 years and 5.0 years, respectively, and 5-year PC incidence was 12.0% and 2.8%, respectively. In LRG, MPD of greater than 3 mm, diabetes mellitus, and presumed branch-duct intraductal papillary mucinous neoplasia (BD-IPMN), defined as PCLs fulfilling any of multilocular formation, multiplicity, or MPD communication, were independent risk factors for PC. In 450 LRG observed for 5 years, 10-year PC incidence was higher in PCLs with our identified risk factors. There was no PC occurrence in PCLs not presumed BD-IPMN after 5-year observation. CONCLUSIONS: Continuous surveillance is needed after 5-year observation, especially in LRG with our identified risk factors. For discontinuing surveillance, PCLs not presumed BD-IPMN at fifth year could be candidates.

Clinical Evaluation of Onrad, A New Low-cost Version of TomoTherapy that Uses Only Static Beams.

OBJECTIVE: This study evaluated the clinical feasibility of a new low-cost TomoTherapy system (OnradTM) and compared it with low-cost linear accelerator models (linacs). METHODS: Various aspects of treatment and cost were compared between Onrad and linacs for 3-dimensional radiotherapy (3DCRT). Dosimetric comparisons of 10 patients each with breast, stage III lung, prostate, head and neck, and cervical cancers were carried out (total 100 plans). RESULTS: Onrad had advantages in terms of availability of long treatment fields and a smaller mechanical footprint. For breast cancers and lung cancers, target dose homogeneity in Onrad plans was better than that in 3DCRT. In the prostate plans, Onrad plans provided superior D95, conformity and homogeneity. The rectum doses of Onrad plans were lower than those with 3DCRT. Onrad plans provided superior homogeneity and D95 in head and neck cancer. The mean dose and V10-40 Gy of the parotid glands was lower using Onrad. In the cervical cancer plans, target doses were similar with both systems. Normal tissue doses were equal. CONCLUSIONS: Onrad is useful in the clinical setting. Onrad can achieve favorable or comparable dose distributions compared with those of 3DCRT in actual clinical treatment of breast, lung, prostate, head and neck, and cervical cancers.

Indocyanine green fluorescence videoangiography for reliable variations of supraclavicular artery flaps.

BACKGROUND: Pedicled flaps are useful for reconstructive surgery. Previously, we often used vascularized supraclavicular flaps, especially for head and neck reconstruction, but then shifted to using thoracic branch of the supraclavicular artery (TBSA) flaps. However, limited research exists on the anatomy of TBSA flaps and on the use of indocyanine green (ICG) fluorescence videoangiography for supraclavicular artery flaps. We utilized ICG fluorescence videoangiography to harvest reliable flaps in reconstructive operations, and describe the results herein. METHODS: Data were retrospectively reviewed from six patients (five men and one woman: average age, 54 years; range, 48-60 years) for whom ICG videoangiography was performed to observe the skin perfusion of a supraclavicular flap after it was raised. Areas where the flap showed good enhancement were considered to be favorable for flap survival. The observation of ICG dye indicated good skin perfusion, which is predictive of flap survival; therefore, we trimmed any areas without dye filling and used the remaining viable part of the flap. RESULTS: The flaps ranged in size from 13×5.5 cm to 17×6.5 cm. One patient received a conventional supraclavicular flap, four patients received a TBSA flap, and one patient received a flap that was considered to be intermediate between a supraclavicular flap and a TBSA flap. The flaps completely survived in all cases, and no flap necrosis was observed. CONCLUSIONS: The TBSA flap is very useful in reconstructive surgery, and reliable flaps could be obtained by using ICG fluorescence videoangiography intraoperatively.

Random mutagenesis of a hyperthermophilic archaeon identified tRNA modifications associated with cellular hyperthermotolerance.

Random mutagenesis for the hyperthermophilic archaeon Thermococcus kodakarensis was established by the insertion of an artificial transposon designed to allow easy identification of the transposon-inserted locus. The phenotypic screening was applied for the isolation of thermosensitive mutants of T. kodakarensis, which resulted in the isolation of 16 mutants showing defective growth at the supraoptimal temperature 93°C. The high occurrence of the mutants suggested that the high thermotolerance of hyperthermophiles was achieved by a combination of diverse gene functions. The transposon insertion sites in two-thirds of the mutants were identified in a group of genes responsible for tRNA modifications including 7-formamidino-7-deaza-guanosine (archaeosine), N1-methyladenosine/N1-methylinosine, N4-acetylcytidine, and N2-dimethylguanosine/N2,N2-dimethylguanosine. LC-MS/MS analyses of tRNA nucleosides and fragments exhibited disappearance of the corresponding modifications in the mutants. The melting temperature of total tRNA fraction isolated from the mutants lacking archaeosine or N1-methyladenosine/N1-methylinosine decreased significantly, suggesting that the thermosensitive phenotype of these mutants was attributed to low stability of the hypomodified tRNAs. Genes for metabolism, transporters, and hypothetical proteins were also identified in the thermosensitive mutants. The present results demonstrated the usefulness of random mutagenesis for the studies on the hyperthermophile, as well as crucial roles of tRNA modifications in cellular thermotolerance.

Molecular profiling of nonalcoholic fatty liver disease-associated hepatocellular carcinoma using SB transposon mutagenesis.

Nonalcoholic fatty liver disease (NAFLD) is the fastest rising cause of hepatocellular carcinoma (HCC) in Western countries; however, the molecular mechanisms that cause NAFLD-HCC remain elusive. To identify molecular drivers of NAFLD-HCC, we performed Sleeping Beauty (SB) transposon mutagenesis screens in liver-specific Pten knockout and in high-fat diet-fed mice, which are murine models of NAFLD-HCC. SB mutagenesis accelerated liver tumor formation in both models and identified 588 and 376 candidate cancer genes (CCGs), respectively; 257 CCGs were common to both screens and were enriched in signaling pathways known to be important for human HCC. Comparison of these CCGs with those identified in a previous SB screen of hepatitis B virus-induced HCC identified a core set of 141 CCGs that were mutated in all screens. Forty-one CCGs appeared specific for NAFLD-HCC, including Sav1, a component of the Hippo signaling pathway and the most frequently mutated gene identified in both NAFLD-HCC screens. Liver-specific deletion of Sav1 was found to promote hepatic lipid accumulation, apoptosis, and fibrogenesis, leading to the acceleration of hepatocarcinogenesis in liver-specific Pten mutant mice. Sav1/Pten double-mutant livers also showed a striking up-regulation of markers of liver progenitor cells (LPCs), along with synergistic activation of Yap, which is a major downstream effector of Hippo signaling. Lastly, Yap activation, in combination with Pten inactivation, was found to accelerate cell growth and sphere formation of LPCs in vitro and induce their malignant transformation in allografts. Our forward genetic screens in mice have thus identified pathways and genes driving the development of NAFLD-HCC.

Freshening by glacial meltwater enhances melting of ice shelves and reduces formation of Antarctic Bottom Water.

Strong heat loss and brine release during sea ice formation in coastal polynyas act to cool and salinify waters on the Antarctic continental shelf. Polynya activity thus both limits the ocean heat flux to the Antarctic Ice Sheet and promotes formation of Dense Shelf Water (DSW), the precursor to Antarctic Bottom Water. However, despite the presence of strong polynyas, DSW is not formed on the Sabrina Coast in East Antarctica and in the Amundsen Sea in West Antarctica. Using a simple ocean model driven by observed forcing, we show that freshwater input from basal melt of ice shelves partially offsets the salt flux by sea ice formation in polynyas found in both regions, preventing full-depth convection and formation of DSW. In the absence of deep convection, warm water that reaches the continental shelf in the bottom layer does not lose much heat to the atmosphere and is thus available to drive the rapid basal melt observed at the Totten Ice Shelf on the Sabrina Coast and at the Dotson and Getz ice shelves in the Amundsen Sea. Our results suggest that increased glacial meltwater input in a warming climate will both reduce Antarctic Bottom Water formation and trigger increased mass loss from the Antarctic Ice Sheet, with consequences for the global overturning circulation and sea level rise.

Coastal polynyas: Winter oases for subadult southern elephant seals in East Antarctica.

Antarctic coastal polynyas are regions of persistent open water and are thought to be key bio-physical features within the sea-ice zone. However, their use by the upper trophic levels of ecosystems remains unclear. A unique bio-physical dataset recorded by southern elephant seals reveals that East Antarctic polynyas are a key winter foraging habitat for male seals. During their post-moult trips from Isles Kerguelen to the Antarctic continental shelf, a total of 18 out of 23 seals visited 9 different polynyas, spending on average 25 ± 20% (up to 75%) of their total trip time inside polynyas. Changes in seal foraging and diving behaviours are observed inside polynyas as compared to outside polynyas. Two polynya usages by seals are observed for the inactive and active polynya phases, pointing to different seasonal peaks in prey abundance. During the active polynya phase, we link seal foraging behaviour to changes in the physical stability of the water-column, which likely impact the seasonal biological dynamics within polynyas.

CyberKnife Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy As First-line Treatments for Imaging-diagnosed Intracranial Meningiomas.

Definitive radiotherapy is an important alternative treatment for meningioma patients who are inoperable or refuse surgery. We evaluated the efficacy and toxicity of CyberKnife-based stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hSRT) as first-line treatments for intracranial meningiomas that were diagnosed using magnetic resonance imaging (MRI) and/or computed tomography (CT). Between February 2005 and September 2015, 41 patients with intracranial meningiomas were treated with CyberKnife-based SRS or hSRT. Eleven of those tumors were located in the skull base. The median tumor volume was 10.4 ml (range, 1.4-56.9 ml). The median prescribed radiation dose was 17 Gy (range, 13-20 Gy to the 61-88% isodose line) for SRS (n = 9) and 25 Gy (range, 14-38 Gy to the 44-83% isodose line) for hSRT (n = 32). The hSRT doses were delivered in 2 to 10 daily fractions. The median follow-up period was 49 months (range, 7-138). The 5-year progression-free survival rate (PFS) for all 41 patients was 86%. The 3-year PFS was 69% for the 14 patients with tumor volumes of ≥13.5 ml (30 mm in diameter) and 100% for the 27 patients with tumor volumes of <13.5 ml (P = 0.031). Grade >2 toxicities were observed in 5 patients (all of them had tumor volumes of ≥13.5 ml). SRS and hSRT are safe and effective against relatively small (<13.5 ml) meningiomas.

Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers.

BACKGROUND: Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients. METHODS: This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization. Among them, 39 and 86 were within or beyond the up-to-seven criteria, respectively. Multivariate Cox proportional hazards analysis was performed to investigate factors that contributed to better prognosis associated with the criteria. RESULTS: Cumulative overall survival (OS) and disease-free survival rates were significantly higher for patients within the up-to-seven criteria compared with those beyond (p = 0.034 and p = 0.001, respectively). Multivariate analysis revealed that low concentrations of des-γ-carboxy prothrombin (DCP) (<150 mAU/ml) and α-fetoprotein (AFP) (<100 ng/ml) were independent contributors to better OS of patients within or beyond the up-to-seven criteria, respectively. Accordingly, the patients were classified as follows: group A (patients within the up-to-seven criteria with DCP <150 mAU/ml), group C (patients beyond the up-to-seven criteria with AFP ≥100 ng/ml), and group B (other patients). OS differed significantly among groups (p < 0.001), and the median survival times of group A, B, and C were 4.2, 2.7, and 1.5 years, respectively. CONCLUSION: The subclassification system incorporating the up-to-seven criteria combined with DCP and AFP levels may serve as better predictors of prognosis that may guide efforts to improve treatment strategies.