[A Case of Solitary Inguinal Lymph Node Metastasis 15 Years after Colorectal Cancer Surgery].

The patient is a 69-year-old man. 17 years ago, a colectomy was performed for colorectal cancer, and a disseminated nodule was found during the operation, so the disseminated nodule was also resected. After the surgery, 12 courses of FOLFOX4 were administered, and there was no recurrence thereafter. He was diagnosed with hepatocellular carcinoma 12 years after the colectomy and underwent liver resection. Fifteen years after the colectomy, a mass shadow appeared in the right inguinal region, and inguinal lymph node metastasis of hepatocellular carcinoma or colorectal cancer was suspected. In the same year, he underwent the tumor resection and histopathological diagnosis revealed colon cancer inguinal lymph node metastasis. After the lymph node resection, he has been followed up for 2 years with no recurrence of colorectal cancer. It is extremely rare to have a solitary inguinal lymph node recurrence 15 years after colon surgery.

Carpal Tunnel Syndrome Caused by a Juxta-articular Myxoma: A Case Report.

Juxta-articular myxoma (JAM) is a rare soft tissue tumour predominantly composed of mucinous tissue and usually found around large joints. We report a 73-year-old woman with a 5-year history of a soft tissue mass in the thenar eminence of the right wrist who presented to our department. An initial diagnosis of a ganglion cyst was made using magnetic resonance imaging (MRI) and the jellied content of the mass by aspiration. Two years after presentation, surgical treatment with tumour resection and carpal tunnel release via the radial approach was performed because the symptoms of carpal tunnel syndrome worsened, and the tumour invaded the carpal tunnel. Histopathological examination revealed a JAM. At the 1-year follow-up, the symptoms of carpal tunnel syndrome had resolved, and no recurrence was confirmed by MRI. Level of Evidence: Level V (Therapeutic).

HMGB2 Promotes De Novo Lipogenesis to Accelerate Hepatocyte Proliferation During Liver Regeneration.

Liver regeneration is a well-orchestrated compensatory process that is regulated by multiple factors. We recently reported the importance of the chromatin protein, a high-mobility group box 2 (HMGB2) in mouse liver regeneration. However, the molecular mechanism remains unclear. In this study, we aimed to study how HMGB2 regulates hepatocyte proliferation during liver regeneration. Seventy-percent partial hepatectomy (PHx) was performed in wild-type (WT) and HMGB2-knockout (KO) mice, and the liver tissues were used for microarray, immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blotting analyses. In the WT mice, HMGB2-positive hepatocytes colocalized with cell proliferation markers. In the HMGB2-KO mice, hepatocyte proliferation was significantly decreased. Oil Red O staining revealed the transient accumulation of lipid droplets at 12-24 hr after PHx in the WT mouse livers. In contrast, decreased amount of lipid droplets were found in HMGB2-KO mouse livers, and it was preserved until 36 hr. The microarray, immunohistochemistry, and qPCR results demonstrated that the expression of lipid metabolism-related genes was significantly decreased in the HMGB2-KO mouse livers. The in vitro experiments demonstrated that a decrease in the amount of lipid droplets correlated with decreased cell proliferation activity in HMGB2-knockdown cells. HMGB2 promotes de novo lipogenesis to accelerate hepatocyte proliferation during liver regeneration.

Protective role of estrogen through G-protein coupled receptor 30 in a colitis mouse model.

Estrogen and its receptors are involved in the pathogenesis of gastrointestinal diseases such as colitis. However, the role of the membrane estrogen receptor G-protein-coupled receptor 30 (GPR30) in colitis is poorly understood. We therefore investigated the effect of estrogen in dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6 mice were administered 1.5% DSS for 5 days and treated with 17ß-estradiol (E2), GPR30 agonist (G1), or GPR30 antagonist (G15) for 8 days. Inflammation grade was evaluated by disease activity index (DAI) and histomorphological score. Colon tissues were immunohistochemically analyzed and revealed high expression of membrane GPR30, histone 3 lysine 36 dimethylation, and lysine 79 trimethylation in normal mouse colon epithelial cells but significantly decreased expression in DSS-treated mice, whereas the expression was partially preserved after treatment with E2 or G1. Colon shortening and DAI were significantly lower in E2- and G1-treated mice compared to DSS-treated mice. Caudal type homeobox 2 (CDX2) expression and cell proliferation differed in normal colon epithelial cells but overlapped in those of DSS-treated mice. Administration of E2 and G1 reduced CDX2 expression and cell proliferation. Altered expression of claudin-2 and occludin were observed in the colonic epithelium of DSS-treated mice, and these changes were significantly lower in the colon of E2- and G1-treated mice. These results indicate that estrogen regulates histone modification, cell proliferation, and CDX2 expression through GPR30, which affects intestinal epithelial barrier function. We conclude that estrogen protects against intestinal epithelial damage through GPR30 by enhancing intestinal epithelial barrier function in DSS-induced colitis in mice.

Sequential Clinical Recovery after Replantation for Complete Finger Amputation in Tamai Zone 1.

Background The clinical results of replantation for an amputated distal finger are functionally acceptable. However, few reports exist regarding sequential clinical postoperative recovery. The purpose of this study was to examine the clinical recovery at every 3 months up to 1 year postoperatively. Methods Nineteen patients (16 patients were men), representing 19 fingers with complete amputation at Tamai's zone 1 and replanted successfully, were included in this study. Total active motion (TAM), grip strength (GS), Semmes-Weinstein monofilament (SW) test result, static two-point discrimination (s2PD), and Disability of the Arm, Shoulder, and Hand (DASH) score questionnaire results were obtained postoperatively at 3, 6, 9, and 12 months. Pulp atrophy and nail deformity were assessed at 12 months postoperatively. Results The postoperative %TAM (compared to the uninjured side, 81.8 ± 18.1 at 3 months vs. 91.5 ± 11.9 at 6 months, p < 0.01), %GS (compared with the uninjured side, 61.3 ± 25.9 at 3 months vs. 78.3 ± 20.4 at 6 months, p = 0.02), s2PD (excellent and good/poor; 7/12 at 3 months vs. 18/1 at 6 months, p < 0.01), and DASH scores (26.1 ± 23.1 at 3 months vs. 12.0 ± 12.9 at 6 months, p < 0.01) recovered significantly from 3 to 6 months but did not change significantly from 6 months onward. The SW test results showed a significant recovery between 3 and 12 months postoperatively (2.83 and 3.61/4.31, 6.65, and undetectable, 1/18 at 3 months vs. 7/12 at 12 months, p = 0.04). The DASH score at 12 months postoperatively was significantly associated with %TAM ( r = -0.64, p < 0.01) and %GS ( r = -0.58, p < 0.01) at 12 months postoperatively and age ( r = 0.52, p = 0.02). Five fingers had pulp atrophy and four fingers had nail deformity. Conclusion This 1-year follow-up study showed the sequential clinical recovery after replantation for complete amputation in Tamai zone 1. Postoperative %TAM, %GS, and the DASH score recovered significantly between 3 and 6 months but significant recovery up to 1 year was not observed.

A Preliminary Pathological Evaluation of Extracellular Volume Fraction with Contrast-enhanced Computed Tomography as a Novel Quantitative Parameter of Pancreatic Fibrosis.

Objective The extracellular volume (ECV) calculated based on contrast-enhanced computed tomography (CT) has been reported as a novel imaging parameter reflecting the morphological change of fibrosis in several parenchymal organs. Our retrospective study assessed the validity of the ECV fraction for diagnosing pancreatic fibrosis and the appropriate imaging condition as the "equilibrium phase". Methods In 27 patients undergoing multiphasic CT and subsequent pancreaticoduodenectomy, we investigated pathological fibrotic changes related to the ECV fraction and conducted analyses using the value obtained by subtracting the equilibrium CT value of the portal vein from that of the abdominal aorta (Ao-PVequilibrium) to estimate eligibility of the equilibrium phase. Results In all patients, the ECV fraction showed a weak positive correlation with the collagenous compartment ratio (r=0.388, p=0.045). All patients were divided into two groups - the high-Ao-PVequilibrium group and low-Ao-PVequilibrium group - based on the median value. No significant correlation was found in the high-Ao-PVequilibrium group, whereas a significant correlation was observed in the low-Ao-PVequilibrium group (r=0.566, p=0.035). Conclusion The ECV fraction is a possible predictive factor for histopathological pancreatic fibrosis. In its clinical application, the eligibility of the "equilibrium phase" may affect the diagnostic capability. It will be necessary to verify the imaging conditions in order to improve the accuracy of the diagnosis.

Reconstruction of a Composite Defect of the Distal Index Finger Using a Chimeric Reverse Flow Second Dorsal Metacarpal Artery Flap: A Case Report.

The reconstruction for mild tissue loss at the distal part of a finger is challenging. We report about a 29-year-old man presenting with traumatic tissue loss at the distal interphalangeal (DIP) joint of the index finger, including skin, bone, and nerve. Reconstruction using two types of flaps was performed. The dorsal skin flap, nourished by the second dorsal metacarpal artery (SDMA) perforator, was elevated. The vascularized second metacarpal bone, nourished by the SDMA, was also elevated. Using the vascular connection between the DMA and the palmar digital artery (PDA), both flaps were raised to the distal part of the finger, and the pivot point was set at the dorsal proximal phalanx. After arthrodesis of the DIP joint with the vascularized second metacarpal bone, the digital nerve was repaired using the cutaneous nerve in the skin flap, and the skin defect was covered using the perforator flap. The postoperative course, including flap survival and bone union, was uneventful. A good indication for the reconstruction of the distal part of a finger with this technique is when the defect sizes of the skin and bone differ and the vascular connection between the SDMA and dorsal branch of PDA is not injured.

Computed Tomography Evaluation of Distal Screw Penetration in Volar Locking Plate Fixation for Intra-Articular Distal Radius Fractures.

PURPOSE: Volar locking plate fixation for distal radius fractures (DRFs) is a technically demanding procedure with a risk of distal screw penetration through the dorsal cortex or the articular surface. This study aimed to investigate the incidence and details of distal screw penetration after volar locking plate fixation for intra-articular DRFs using a CT scan and to evaluate the relationship between the incidence of screw penetration and fracture comminution severity and the clinical complications of screw penetration. METHODS: This was a retrospective case series of 91 adult patients (mean age, 63 years; 27 men) who underwent volar locking plate fixation for intra-articular DRFs from 2015 to 2018. The positioning of the distal screws was evaluated using a postoperative CT scan, and radiological outcomes were compared between the AO C1 and C3 groups. At the final follow-up, tendon rupture and arthritis severity were assessed as clinical complications of dorsal and intra-articular screw penetration. RESULTS: Distal screw penetration was observed in 44 wrists (48%), dorsal cortex screw penetration in 34, intra-articular screw penetration in 13, and both dorsal cortex and intra-articular screw penetration in three. The incidence of intra-articular screw penetration was significantly higher in the C3 group than in the C1 group. No tendon rupture was observed. Multivariable analysis revealed that intra-articular screw penetration was significantly related to high severity of arthritis. CONCLUSIONS: Approximately half of the study patients with intra-articular DRFs had distal screw penetration. The incidence of intra-articular screw penetration was associated with the severity of fracture comminution, and the intra-articular screw penetration was associated with the incidence of early radiocarpal arthritis. Intra-articularly penetrating screws should be replaced as soon as they are discovered, regardless of the length of penetrated screw or absence of patients' subjective symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

An alternative option of the retroperitoneal laparoscopic approach for limited hepatectomy for recurrent hepatocellular carcinoma at the transected edge after previous hepatectomy.

Laparoscopic hepatectomy is safely performed with minimal invasiveness on patients with recurrent liver tumors after previous hepatectomy. However, it is still difficult to dissect and expose the operative field at the transected edge or plane after open right hepatectomy, even for limited resection by a laparoscopic approach, due to severe adhesion to the surrounding peritoneum or organs. We herein applied the retroperitoneal laparoscopic approach to limited resection of the dorsal surface at the transected edge of Couinaud's segment 6 after previous repeated hepatectomies in a patient with recurrent hepatocellular carcinoma (HCC) by avoiding severe intra-abdominal adhesion. We safely resected recurrent HCC via the retroperitoneal space. This approach is a useful and alternative option for laparoscopy which minimizes the dissecting time and avoids organ injury on the right side of the transected area of the liver after hepatectomy in patients with liver malignancies.

Clinical Results of Surgical Treatment for Comminuted Radial Head and Neck Fracture: Headless Compression Screws Versus Plate Fixation.

Background: We surgically treated comminuted radial head and neck fractures using headless compression screws, including multiple screws for the radial head and a single oblique screw for the radial neck. This study aimed to compare the clinical and radiological results for comminuted radial head and neck fractures between surgery using headless compression screws with a single oblique screw for the radial neck, our new procedure, and a plate system precontoured to the proximal radius. Methods: This retrospective study included 23 patients (11 and 12 in the screw and plate groups, respectively). The fractures were type 3 according to the Mason-Johnston classification modified by Broberg and Morrey. Clinical outcomes analyzed included the motion range of the elbow and forearm, Mayo Elbow Performance Score, and radiological assessments. In addition, postoperative complications were also investigated. The average follow-up was 18 months. Results: The bone union was achieved in all the patients, and there were no significant differences in clinical outcomes and radiological assessments except forearm supination (p = 0.02). Furthermore, additional surgical procedures were performed in one and five patients in the screw and plate groups, respectively (p = 0.16). Posterior nerve palsy was observed in two patients in the plate group. Complications were observed in one and six patients in the screw and plate groups, respectively (p = 0.07). Conclusion: Both surgical procedures achieved good clinical and radiological outcomes with bone and ligament injury repair. The screw group had a greater range of forearm supination than the plate group.

Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis.

Background: Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods: Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results: Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions: Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.

Frailty and muscle weakness in elderly patients with asthma and their association with cumulative lifetime oral corticosteroid exposure.

BACKGROUND: Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma. METHODS: We studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength. RESULTS: Thirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes. CONCLUSIONS: Cumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma.

Arthroscopic Reduction and Internal Fixation for Peritrapezium Traumatic Axial Carpal Dislocation: A Case Report.

Axial carpal dislocations and fracture-dislocations are rare injuries involving derangement of the carpal arches. Several surgical approaches have been reported as a means of treatment, including the use of closed or open reduction and internal fixation. However, to our knowledge, surgical treatment using arthroscopy has not been reported so far. Here we present the case of a 54-year-old man who experienced peritrapezium axial carpal dislocation while reversing his car. Minimally invasive surgery using arthroscopy was performed because of severe swelling of the hand. Reduction under arthroscopic assistance using midcarpal portals was performed based on the relationship between the trapezium and trapezoid, and fixed wires were inserted. Wires were removed at six weeks postoperatively, and range-of-motion exercises of the wrist joint were started. At one-year postoperative follow-up, the patient was asymptomatic, with no difficulties while performing daily activities and work. Computer tomography images revealed an anatomical carpal arch without traumatic arthrosis. Arthroscopy-assisted surgery enabled us to anatomically reduce fracture-dislocation of the trapezium and assess the injury path.

Profiling a single-stranded DNA region within an rDNA segment that affects the loading of bacterial condensin.

Bacterial condensin preferentially loads onto single-stranded DNA (ssDNA) in vitro and onto rDNA in vivo to support proper chromosome compaction. Thus, the actively transcribing rDNA would provide the ssDNA region for the loading of bacterial condensin. We attempted to detect the ssDNA region in the rrnI gene in situ. Non-denaturing sodium bisulfite treatment catalyzed the conversion of cytosines to thymines (CT-conversion) at the melted DNA of a genome. Using next-generation sequencing, we generated an average of 11,000 reads covering each cytosine on the rDNA segment. In principle, the CT-conversion rate is an accurate guide to detect ssDNA segment. We detected multiple ssDNA segments throughout the rDNA. The deletion mutations of the rDNA hindered the ssDNA formation at the 100-500 bp segment downstream of the promoter. These data support the idea that the ssDNA segment plays a crucial role as the condensin-loading site and suggest the mechanism of condensin loading onto rDNA.

Successful Right Hepatectomy for Recurrent Liver Tumor Originating from an Inferior Vena Cava Leiomyosarcoma: A Follow-Up Case Report.

BACKGROUND Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignancy, and complete resection may provide better patient survival. Hepatectomy for intrahepatic tumor recurrence has not been previously reported. CASE REPORT A 58-year-old woman underwent resection of an IVC-LMS with en bloc nephrectomy, adrenalectomy, and retroperitoneal soft tissue resection without IVC reconstruction 3 years 8 months ago. Twenty-nine months after the primary operation, a solitary intrahepatic liver tumor was found adjacent to the right and middle hepatic veins during imaging follow-up. The patient was diagnosed with LMS recurrence. As her liver functional parameters permitted major hepatectomy, right hepatectomy combined with resection of the vena cava wall leaving a tumor-free margin and securing the confluence of the middle hepatic vein were successfully accomplished via an anterior approach, without adverse events. Intrahepatic metastasis of LMS invading the vena cava wall has been diagnosed historically. Her postoperative course was uneventful, and at 1-year follow-up after the second surgery, she was observed to have no tumor relapse without any adjuvant treatment. Previous reports have shown that IVC-LMS is often observed, and operative risk or prognosis is based on the extension of the LMS toward the hepatic veins or cardiac atrium. CONCLUSIONS Radical hepatectomy for recurrent IVC-LMS has not been previously reported, and our case experience revealed that a challenging surgical intervention resulting in complete tumor removal can provide good survival outcomes.

A rare case of long-term survival of a patient who underwent radical operations for sextuple malignancies.

Multiple cancer patients who achieve long-term survival are sometimes encountered. Multiple carcinogenesis may occur due to genetic or environmental characteristics. We report the case of a 74-year-old woman who was diagnosed with synchronous double carcinoma of the duodenal papilla and gall bladder without clinical symptoms, who underwent postoperative follow-up for familiar adenomatous polyposis coli with multiple colonic adenocarcinomas, ileal adenocarcinoma, left urinary tract neoplasm, and left upper lobe lung adenocarcinoma. Computed tomography also showed an intraductal papillary mucinous neoplasm of the pancreas and a lesion that was suspected to be uterine body carcinoma; however, they did not show any clear malignant behavior. No metastatic lesions of either of these biliary cancers were observed. Based on preoperative diagnostic imaging, subtotal stomach preserving pancreaticoduodenectomy with gall bladder bed liver resection with D2 lymphadenectomy was planned and R0 resection was achieved. The postoperative histological diagnosis showed early carcinoma of the duodenal papilla and gall bladder pyloric gland adenoma without node metastasis. The postoperative course was uneventful and the patient had a good prognosis without tumor recurrence or new malignant lesions for two years after the last operation, without adjuvant therapy. Six metachronous carcinomas of eight different organ neoplasms were diagnosed, which is rare. This represents the first reported case of ampullary carcinoma in a patient with sextuple cancer.

Prognostic Value of Repeat Hepatectomy for Hepatocellular Carcinoma Patients.

BACKGROUND/AIM: The potential for repeat hepatectomy has been increasing in hepatocellular carcinoma (HCC) patients. PATIENTS AND METHODS: To assess its significance, we examined the clinical features, surgical records, and survival of 279 HCC patients who underwent hepatectomy as primary treatment. Patients were divided into three groups: single hepatectomy without HCC relapse in 97 patients (Group 1), single hepatectomy with HCC relapse in 133 patients (Group 2) and repeat hepatectomy for HCC relapse in 49 patients (Group 3). Group 3 was divided into three subgroups. Multiple, larger size (>5 cm), and confluent nodular HCC. RESULTS: Child-Pugh B patients were significantly higher in Group 2 (p<0.01). The prevalence of histological vascular involvement was significantly higher in Group 2 than in the other groups (p<0.01). Although Group 2 showed significantly poorer survival (p<0.01), the 10-year overall survival in Groups 1 and 3 was over 70% but not different between groups. The relapse-free survival period was significantly correlated with overall survival, and patients with a cancer-free period of over 36 months showed significantly better 10-year survival rates than those with a period of less than 36 months (p<0.01). Patients undergoing 3 or more repeat hepatectomies also showed good survival periods. CONCLUSION: Careful follow-up and proper decision-making in terms of repeat hepatectomy with multimodal treatments including novel chemotherapies upon assessment of postoperative tumor relapse are important in HCC patients to prolong survival.

Simultaneous Open Reduction and Corrective Osteotomy for a Child With Lateral Condylar Fracture and Cubitus Varus Deformity Following Supracondylar Fracture: A Case Report.

Posttraumatic cubitus varus deformity in pediatric patients may cause second fractures of the distal humerus. Corrective osteotomy is used to obtain good alignment and is generally performed for patients with prolonged deformity or bony union after fracture. We report the case of a 10-year-old boy who presented with elbow pain after falling. Plain radiography showed lateral condylar fracture and cubitus varus deformity. This injury was the fourth fracture of the same distal humerus. Open reduction and internal fixation for lateral condylar fracture and lateral closing wedge osteotomy for cubitus varus deformity were performed simultaneously. At the last follow-up, one and a half years after operation, plain radiography showed closure of the physis of the distal humerus, and coronal alignment was maintained. The patient was asymptomatic and satisfied with cosmetic issues. There was no fracture after two surgical procedures simultaneously.

Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration.

Liver regeneration is an extraordinarily complex process involving a variety of factors; however, the role of chromatin protein in hepatocyte proliferation is largely unknown. In this study, we investigated the functional role of high-mobility group box 2 (HMGB2), a chromatin protein in liver regeneration using wild-type and HMGB2-knockout (KO) mice. Liver tissues were sampled after 70% partial hepatectomy (PHx), and analyzed by immunohistochemistry, western blotting and flow cytometry using various markers of cell proliferation. In WT mice, hepatocyte proliferation was strongly correlated with the spatiotemporal expression of HMGB2; however, cell proliferation was significantly delayed in hepatocytes of HMGB2-KO mice. Quantitative PCR demonstrated that cyclin D1 and cyclin B1 mRNAs were significantly decreased in HMGB2-KO mice livers. Interestingly, hepatocyte size was significantly larger in HMGB2-KO mice at 36-72 h after PHx, and these results suggest that hepatocyte hypertrophy appeared in parallel with delayed cell proliferation. In vitro experiments demonstrated that cell proliferation was significantly decreased in HMGB2-KO cells. A significant delay in cell proliferation was also found in HMGB2-siRNA transfected cells. In summary, spatiotemporal expression of HMGB2 is important for regulation of hepatocyte proliferation and cell size during liver regeneration.