Self-Folding Macromolecular Drug Carrier for Cancer Imaging and Therapy.

Nano-sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano-carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self-folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self-folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti-tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self-folding molecular design underscore its promise for cancer diagnosis and treatment.

Outcomes and management of delayed complication after severe blunt liver injury.

BACKGROUND: The treatment of delayed complications after liver trauma such as bile leakage (BL) and hepatic artery pseudoaneurysms (HAPs) is difficult. The purpose of this study is to investigate the outcomes and management of post-traumatic BL and HAPs. METHODS: We retrospectively evaluated patients diagnosed with blunt liver injury, graded by the American Association for the Surgery of Trauma Liver Injury Scale, who were admitted to our hospital between April 2010 and December 2019. Patient characteristics and treatments were analyzed. RESULTS: A total of 176 patients with blunt liver injury were evaluated. Patients were diagnosed with grade I-II liver injury (n = 127) and with grade III-V injury (n = 49). BL was not observed in patients with grade I-II injury. Eight patients with grade III-V injury developed BL: surgical intervention was not needed for six patients with peripheral bile duct injury, but hepaticojejunostomy was needed for two patients with central bile duct injury. Out of 10 patients with HAPs, only three with grade I-II injury and one with grade III-V were treated conservatively; the rest six with grade III-V injury required transcatheter arterial embolization (TAE). All pseudoaneurysms disappeared. CONCLUSIONS: Severe blunt liver injury causing peripheral bile duct injury can be treated conservatively. In contrast, the central bile duct injury requires surgical treatment. HAPs with grade I-II injury might disappear spontaneously. HAPs with grade III-V injury should be considered TAE.

Short-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma in older patients: a propensity score matching analysis.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) requiring surgical treatment in older patients has been continuously increasing. This study aimed to examine the safety and feasibility of performing laparoscopic liver resection (LLR) versus open liver resection (OLR) for HCC in older patients at a Japanese institution. METHODS: Between January 2010 and June 2021, 133 and 145 older patients (aged ≥ 70 years) who were diagnosed with HCC underwent LLR and OLR, respectively. Propensity score matching (PSM) analysis with covariates of baseline characteristics was performed. The intraoperative and postoperative data were evaluated in both groups. RESULTS: After PSM, 75 patients each for LLR and OLR were selected and the data compared. No significant differences in demographic characteristics, clinical data, and operative times were observed between the groups, although less than 10% of cases in each group underwent a major resection. Blood loss (OLR: 370 mL, LLR: 50 mL; P < 0.001) was lower, and the length of postoperative hospital stay (OLR: 12 days, LLR: 7 days; P < 0.001) and time to start of oral intake (OLR: 2 days, LLR: 1 day; P < 0.001) were shorter in the LLR group than in the OLR group. The incidence of complications ≥ Clavien-Dindo class IIIa was similar between the two groups. CONCLUSIONS: LLR, especially minor resections, is safely performed and feasible for selected older patients with HCC.

Intrahepatic Glissonean Approach for Laparoscopic Bisegmentectomy 7 and 8 With Root-Side Hepatic Vein Exposure.

BACKGROUND: Laparoscopic anatomic liver resections of the posterosuperior segments are technically demanding procedures.1-5 The segments are located in a deep-seated area of the liver surrounded by the ribs and the diaphragm, making forceps manipulation difficult. To overcome this limitation, an intrahepatic Glissonean approach and exposure of the hepatic veins from the root side was applied.6-10 The authors describe the technical aspects of performing a bisegmentectomy 7-8. METHODS: Liver parenchymal transection was initiated from the ventral aspect of the root of the middle hepatic vein, which often runs in the intersegmental plane, identifying the Glissonean pedicle of segment 8 (G8). After dissection of the G8, segmentectomy 8 was performed through identification of the ischemic area. After complete mobilization of the right lobe, the Glissonean pedicle of segment 7 (G7), which runs relatively near the liver surface,9, 10 was marked using ultrasonography. After division of the G7, a wide dissection between the caudate lobe and segment 7 was performed and connected to the previously dissected plane from the dorsal side of the right hepatic vein (RHV). Finally, bisegmentectomy 7-8 was performed with RHV resection because of tumor invasion. RESULTS: The operation time was 510 min, and the estimated blood loss was 150 ml. The patient was discharged on postoperative day 10 without any complications. CONCLUSIONS: Application of the intrahepatic Glissonean approach and exposure of the major hepatic veins from their roots using unique laparoscopic principles allows a safe performance of bisegmentectomy 7-8.

Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer.

The HLA-A*24:02-restricted peptide vaccine targeting Wilms' tumor 1 (WT1) (WT1 vaccine) is a promising therapeutic strategy for ovarian cancer; however, its efficacy varies among patients. In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events. We assessed Wilms' tumor 1-specific cytotoxic T lymphocytes (WT1-CTLs) and Wilms' tumor 1 peptide-specific immunoglobulin G (WT1235-IgG). After vaccination, the percentage of tetramer high-avidity population of WT1-CTLs among CD8+ T lymphocytes (%tet-hi WT1-CTL) and the WT1235-IgG titer increased significantly, although the values were extremely low or below the limit of detection before vaccination (%tet-hi WT1-CTL: 0.003%-0.103%.; WT1235-IgG: <0.05-0.077 U/mL). Patients who had %tet-hi WT1-CTL of ≥0.25% (n=6) or WT1235-IgG of ≥0.10 U/mL (n=12) had a significantly longer progression-free survival than those of patients in the other groups. In addition, an increase in WT1235-IgG corresponded to a significantly longer progression-free survival (P=0.0496). In patients with systemic inflammation, as evidenced by elevated C-reactive protein levels, the induction of tet-hi WT1-CTL or WT1235-IgG was insufficient. Decreased serum albumin levels, multiple tumor lesions, poor performance status, and excess ascites negatively influenced the clinical effectiveness of the WT1 vaccine. In conclusion, the WT1 vaccine induced antigen-specific cellular and humoral immunity in patients with refractory ovarian cancer. Both %tet-hi WT1-CTL and WT1235-IgG levels are prognostic markers for the WT1 vaccine.

Laparoscopic Anatomic Liver Resection of the Dorsal Part of Segment 8 Using an Hepatic Vein-Guided Approach.

BACKGROUND: Laparoscopic anatomic liver resection is considered highly challenging, especially in segment 8 (S8), owing to the limited angle of the laparoscope and limited manipulation of the surgical instrument1,2. Additionally, resection is technically difficult when approaching the more peripheral branches since the Glissonean pedicle of S8 has several variations3 and is far from the hepatic hilum. The hepatic vein (HV)-guided approach involves entering from the cranial side of the liver while overcoming these difficulties with the unique view and techniques of laparoscopy4,5. We describe laparoscopic anatomic resection of the dorsal part of S8 using the HV-guided approach for hepatocellular carcinoma. METHODS: The drainage vein of segment 8 (V8), which often runs between the ventral and dorsal parts of S86,7, was exposed from the confluence of the middle HV to the periphery. The dorsal Glissonean branch of S8 (G8dor) was identified by deep dissection of the parenchyma on the right side of the V8. The right HV (RHV) was exposed toward the periphery after dissecting the G8dor. Liver parenchymal dissection was completed by connecting the demarcation line and the RHV. RESULTS: The total operation time was 319 min, estimated blood loss was 5 mL, and the patient was discharged on postoperative day 6 with no complications. CONCLUSION: Laparoscopic anatomic resection of the dorsal parts of S8 could be safely performed by exposing the HVs from their roots and using the HVs as a landmark to identify the intrahepatic Glissonean pedicles.

Boosting Auto-Induction of Recombinant Proteins in Escherichia coli with Glucose and Lactose Additives.

BACKGROUND: Auto-induction is a convenient way to produce recombinant proteins without inducer addition using lac operon-controlled Escherichia coli expression systems. Auto-induction can occur unintentionally using a complex culture medium prepared by mixing culture substrates. The differences in culture substrates sometimes lead to variations in the induction level. OBJECTIVES: In this study, we investigated the feasibility of using glucose and lactose as boosters of auto-induction with a complex culture medium. METHODS: First, auto-induction levels were assessed by quantifying recombinant GFPuv expression under the control of the T7 lac promoter. Effectiveness of the additive-containing medium was examined using ovine angiotensinogen (tac promoter-based expression) and Thermus thermophilus manganese-catalase (T7 lac promoter-based expression). RESULTS: Auto-induced GFPuv expression was observed with the enzymatic protein digest Polypepton, but not with another digest tryptone. Regardless of the type of protein digest, supplementing Terrific Broth medium with glucose (at a final concentration of 2.9 g/L) and lactose (at a final concentration of 7.6 g/L) was successful in obtaining an induction level similar to that achieved with a commercially available auto-induction medium. The two recombinant proteins were produced in milligram quantity of purified protein per liter of culture. CONCLUSION: The medium composition shown in this study would be practically useful for attaining reliable auto-induction for E. coli-based recombinant protein production.

How-I-do-it: laparoscopic left medial sectionectomy utilizing a cranial approach to the middle hepatic vein and Laennec's capsule.

BACKGROUND: Laparoscopic anatomic liver resection is technically demanding, given the need to safely isolate the Glissonean pedicles and expose the hepatic veins (HVs) on the liver parenchyma cut surface. Laennec's capsule is observed around the Glissonean pedicles and root of the HVs. However, its existence, particularly on the peripheral side of the HVs, remains controversial. Herein, we describe Laennec's capsule-related histopathological findings around the HVs and a safe laparoscopic left medial sectionectomy utilizing Laennec's capsule. METHODS: The extrahepatic Glissonean approach was performed by connecting Gates II and III, in accordance with Sugioka's Gate theory. Liver parenchymal transection commenced along the demarcation line, which is between the medial and lateral sections, and the G4 was dissected during transection. Subsequently, via the outer-Laennec approach, the middle hepatic vein (MHV) was exposed from the root side in cranial view, while Laennec's capsule was preserved. Parenchymal transection was completed while connecting the MHV with the demarcation line. We obtained the membrane surrounding the HVs and performed histopathological examinations. RESULTS: Six patients underwent laparoscopic left medial sectionectomy from February 2012 to November 2020. There were no cases involving complications (Clavien-Dindo classification; grade II or higher), open-surgery conversion, transfusion, or surgery-related death. The histopathological findings showed Laennec's capsule surrounding both the trunk of the major HVs and the peripheral side of the HVs. CONCLUSIONS: A cranial approach to the major HVs utilizing Laennec's capsule is a feasible and advantageous procedure for laparoscopic left medial sectionectomy. We propose that Laennec's capsule surrounds the entire length of the HVs.

Identification of a radical SAM enzyme involved in the synthesis of archaeosine.

Archaeosine (G+), 7-formamidino-7-deazaguanosine, is an archaea-specific modified nucleoside found at the 15th position of tRNAs. In Euryarchaeota, 7-cyano-7-deazaguanine (preQ0)-containing tRNA (q0N-tRNA), synthesized by archaeal tRNA-guanine transglycosylase (ArcTGT), has been believed to be converted to G+-containing tRNA (G+-tRNA) by the paralog of ArcTGT, ArcS. However, we found that several euryarchaeal ArcSs have lysine transfer activity to q0N-tRNA to form q0kN-tRNA, which has a preQ0 lysine adduct as a base. Through comparative genomics and biochemical experiments, we found that ArcS forms a robust complex with a radical S-adenosylmethionine (SAM) enzyme named RaSEA. The ArcS-RaSEA complex anaerobically converted q0N-tRNA to G+-tRNA in the presence of SAM and lysine via q0kN-tRNA. We propose that ArcS and RaSEA should be considered an archaeosine synthase α-subunit (lysine transferase) and ß-subunit (q0kN-tRNA lyase), respectively.

Right Hepatic Vein Reconstruction with an Autologous Jugular Vein Graft to Expand the Surgical Indications for Liver Tumors.

PURPOSE: We herein report 3 cases in which the right hepatic vein (RHV) involved with a liver tumor was reconstructed using an autologous jugular vein graft to raise the curability and to increase the functional volume of the liver remnant (LR). CASE 1: Cholangiocellular carcinoma (diameter 6.0 cm) in the left lobe invaded the RHV, the branch of the RHV which drains segment 7 (V7) and the middle hepatic vein (MHV). Because the ratio of the LR drained by the inferior right hepatic vein (IRHV) was 26.7%, extended left lobectomy including MHV with RHV and V7 reconstruction was carried out, resulting in a good outcome and an uneventful operative course. Surgical margins on the liver resection plane and at the IVC were 5 mm and partially zero, respectively. CASE 2: Cholangiolocellular carcinoma (diameter 9.0 cm) in the left lobe and the anterior segment invaded the RHV, V7, IVC and bile duct. In this case, the IRHV was present and not involved with the tumor. Because the ratio of the LR drained by the IRHV was 26.1%, left hepatic trisectionectomy with RHV, V7, IVC, and bile duct reconstruction was performed, leading to a good operative course. Surgical margins on the liver resection plane and at the IVC were 8 mm and partially zero, respectively. CASE 3: Hepatocellular carcinoma (diameter 2.7 cm) in segment 7 invaded the RHV. Because the hepatic functional reserve had decreased due to the presence of hepatitis C virus, extended subsegmentectomy (segment 7) with RHV reconstruction was performed, thus resulting in a sufficiently maintained LR function. Surgical margin on the liver resection plane was 7 mm. CONCLUSION: RHV reconstruction with an autologous jugular vein graft is considered to be useful for safely expanding the surgical indications for liver tumors.

Useful technique for draining a large cystic tumor through the round ligament in laparoscopic left hemihepatectomy.

INTRODUCTION: Some cystic liver tumors are huge when the diagnosis is made or surgery is needed. Although reducing tumor size by preoperative aspiration or drainage of the contents of the cystic tumor is helpful for liver resection, such procedures have a risk of tumor dissemination. MATERIALS AND SURGICAL TECHNIQUE: After the round ligament was dissected, a 12-Fr drainage catheter was inserted into the tumor via the round ligament under ultrasonography. At that time, close attention was paid to avoid having the catheter deviate outside the round ligament. Through the inserted catheter, fluid was drained from the cystic lesion, and the stump of the round ligament was clipped to avoid fluid leakage. The left Glissonian pedicle was then taped. Laparoscopic left hemihepatectomy was performed under a good operative field because of tumor shrinkage. DISCUSSION: Three cases underwent these procedures without any spillage of the contents of the cystic tumor. This method is useful for the reduction of tumor size and has a low risk of intra-abdominal leakage of the contents, resulting in a secure and good operative field.

Usefulness of a CT-guided hookwire marking in laparoscopic partial hepatectomy for hepatocellular carcinoma invisible on ultrasonography.

INTRODUCTION: The intra-operative detection of hepatocellular carcinoma (HCC) by ultrasonography is indispensable for laparoscopic partial hepatectomy. However, it is occasionally difficult to localize an HCC on an ultrasound in chronic liver disease. Two cases of partial hepatectomy using hookwire marking under CT guidance are presented. MATERIALS AND SURGICAL TECHNIQUE: The location of the HCC was identified by CT scan, and the puncture site was determined. A hookwire system, made of a stainless steel hook, was used to localize the HCC. The hookwire was placed percutaneously close to the HCC, and then the patient was taken to the operating room as soon as possible. After identification of the hookwire marker, the cutting line was determined on the liver surface to ensure a sufficient surgical margin in laparoscopic partial hepatectomy. DISCUSSION: Two cases underwent these procedures with easy intra-operative marking of the resection area. This technique facilitates safe laparoscopic partial hepatectomy for an HCC that is invisible on ultrasound.

Selective control of up-regulated and down-regulated genes by temporal patterns and doses of insulin.

Secretion of insulin transiently increases after eating, resulting in a high circulating concentration. Fasting limits insulin secretion, resulting in a low concentration of insulin in the circulation. We analyzed transcriptional responses to different temporal patterns and doses of insulin in the hepatoma FAO cells and identified 13 up-regulated and 16 down-regulated insulin-responsive genes (IRGs). The up-regulated IRGs responded more rapidly than did the down-regulated IRGs to transient stepwise or pulsatile increases in insulin concentration, whereas the down-regulated IRGs were repressed at lower concentrations of insulin than those required to stimulate the up-regulated IRGs. Mathematical modeling of the insulin response as two stages-(i) insulin signaling to transcription and (ii)transcription and mRNA stability-indicated that the first stage was the more rapid stage for the down-regulated IRGs, whereas the second stage of transcription was the more rapid stage for the up-regulated IRGs. A subset of the IRGs that were up-regulated or down-regulated in the FAO cells was similarly regulated in the livers of rats injected with a single dose of insulin. Thus, not only can cells respond to insulin but they can also interpret the intensity and pattern of signal to produce distinct transcriptional responses. These results provide insight that may be useful in treating obesity and type 2 diabetes associated with aberrant insulin production or tissue responsiveness.

Advanced hepatocellular carcinoma with hepatic vein tumor thrombosis and renal dysfunction after hepatic arterial infusion chemotherapy effectively treated by liver resection with active veno-venous bypass: report of a case.

BACKGROUND: Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass. CASE PRESENTATION: A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery. CONCLUSION: In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension.

Screening for Identification of Personalized Food to Promote Adiponectin Secretion in Patients with Cancer.

BACKGROUND/AIM: Adiponectin is secreted specifically from adipose tissue. Low serum adiponectin levels may cause metabolic syndrome, which is also a risk factor for carcinogenesis. Several studies have suggested a negative correlation between adiponectin and risk of cancers. This study examined the adiponectin secretion-promoting effect of food ingredients in adipose-derived stem cells (ADSCs) obtained from patients with cancer. PATIENTS AND METHODS: ADSCs from 7 lifestyle disease cancer patients were differentiated into adipocytes. Subsequently, the adipocytes were treated with 49 food constituents. The adiponectin levels in cell culture supernatants were measured after 48 and 96 h. RESULTS: Soy genistein extract, lychee low-molecular-weight polyphenol, olive extract and turmeric promoted adiponectin secretion. CONCLUSION: Food constituents that promoted adiponectin secretion were identified using ADSCs derived from patients. This study suggested the possibility of a new treatment approach to prevent cancer recurrence.

Safety of Emulsifying Lipid Formulation Containing Omega-3 Polyunsaturated Fatty Acids for Patients with Crohn's Disease.

BACKGROUND/AIM: The efficacy of omega-3 supplementation by oral capsule for patients with Crohn's disease (CD) remains controversial. We investigated the safety and efficacy of an omega-3 emulsified formulation. PATIENTS AND METHODS: Six patients with CD in remission participated in this open-label clinical trial. Patients ingested one bottle (100 ml) of the test formulation (IMARK S®) daily for 28 days. After a 1-month washout period, patients ingested two bottles of the formulation daily for 28 days. Anthropometric and blood tests were performed before and after each intervention. RESULTS: The omega-3 emulsifying formulation was safe with minimal side-effects. Body weight and body-mass index were not altered; however, CD activity index scores tended to decrease after ingested one bottle of formulation. Blood tests revealed no severe adverse effects. CONCLUSION: Supplementation with an omega-3 emulsifying formulation can be safe and useful for maintaining remission in patients with CD and warrants further studies.

Extra-Adrenal Retroperitoneal Paraganglioma with Extensive Duodenal Invasion and Inferior Vena Cava Tumor Thrombus.

We report a case of extra-adrenal retroperitoneal paraganglioma (RP) with extensive duodenal invasion and tumor thromboses both in the right testicular vein and in the inferior vena cava (IVC). Because there was rigid adherence between the RP and the abdominal aorta, pancreatoduodenectomy with replacement of the IVC and aorta was performed for complete surgical resection. In the present case, both the mode of progression of the RP and the surgical approach were extremely rare.

[A case of AFP-producing esophagogastric junction cancer with liver metastases with a good response to chemotherapy].

A 62-year-old man was diagnosed with esophagogastric junction cancer following esophagogastroduodenoscopy in response to hematemesis. Although liver metastasis was detected during surgery, a total gastrectomy and lower esophagus resection for local control was performed. Alpha-fetoprotein(AFP)-producing tumor with hepatoid adenocarcinoma was diagnosed on the basis of the pathological examination. Serum AFP levels remained high postoperatively and multiple liver metastases were detected on computed tomography imaging. After 6 courses of chemotherapy with S-1 and cisplatin (CDDP), a significant reduction in the size of the liver metastases and a decrease of serum AFP levels were achieved. Postoperative 2-year tumor control using S-1 single agent chemotherapy was obtained. AFP-producing esophagogastric junction cancer has a poor prognosis. This case raises the possibility that long-term survival can be obtained by combining surgery for local control with systemic chemotherapy.

[An examination of the utility of high-precise radiation therapies for the recurrence of postoperative esophageal cancer].

We analyzed 16 cases (23 therapeutic sites) of post-operative recurrence of esophageal cancers that were treated with high-precise radiation therapies.The recurrence sites were cervical lymph nodes (5 cases), superior mediastinal lymph nodes (5 cases), posterior mediastinal lymph nodes (3 cases), regional lymph nodes with anastomosis (2 cases), abdominal paraaortic lymph node (3 cases), and regions with hematogenous metastasis (5 cases: liver, lung, spleen, and dissemination to the diaphragm bottom).By recurrence number, 10 cases presented with a single lesion, and 6 cases had multiple lesions.The effect of the treatment was complete response (CR) in all cases, and 6 cases maintained CR.The median of the overall survival after radiotherapy was 562 (132-1,231) days.Analysis of the prognostic factors for the overall survival from a recurrence revealed that the metastatic number (single) (p=0.003), and the metastatic pattern(hematogenous metastasis) (p= 0.004), significantly improved prognosis.We conclude that radiotherapy is an option to extend prognosis in some recurrence cases.

Restoration of scarred vocal folds using 5 amino acid-deleted type hepatocyte growth factor.

OBJECTIVES/HYPOTHESIS: Our previous studies demonstrated a regenerative effect of recombinant human hepatocyte growth factor (HGF) on vocal fold scarring using full-length HGF. However, clinical application has not yet been achieved because of the lack of a good manufacturing practice (GMP) for full-length HGF. Another natural form of human HGF, 5 amino acid-deleted type HGF (dHGF), has been newly produced under a GMP procedure. In the current study, we investigated the effect of dHGF in comparison with full-length HGF for the treatment of vocal fold scars using a canine model. STUDY DESIGN: Prospective animal experiment. METHODS: The vocal folds of nine beagles were unilaterally injured. Four weeks after injury, the vocal folds were treated with an intracordal injection of full-length HGF (full HGF group), dHGF (dHGF group), or phosphate-buffered saline (sham group). Vibratory and histological examinations were performed for each group 6 months after injury. RESULTS: Vibratory examinations demonstrated significantly lower phonation threshold pressure and a higher ratio of normalized mucosal wave amplitude in both the full HGF and dHGF groups as compared to the sham group. Histological examination showed restoration of hyaluronic acid in both the full HGF and dHGF groups as compared to the sham group. No significant differences were observed for each parameter between the full HGF group and the dHGF group. CONCLUSIONS: dHGF showed the same potential for regenerative effects on vocal fold scars as full-length HGF. dHGF should be applicable for human clinical trials in patients with vocal fold scars.