[Collision cancer of primary squamous cell carcinoma and adenocarcinoma in the stomach after treatment for a non-Hodgkin's lymphoma of diffuse large B cell type:a case report].

We report the case of a 61-year-old woman with a collision cancer of primary squamous cell carcinoma (SCC) and adenocarcinoma in the stomach that was cured surgically. She achieved complete remission after treatment (R-CHOP and radiation therapy;40.8Gy/22Fr) for a non-Hodgkin's lymphoma of diffuse large B cell type from September 2016 to April 2017. In August 2018, endoscopic findings showed a type 3 tumor with a white coat on the posterior wall of the upper gastric body. A biopsied specimen showed that the tumor was a SCC. Total gastrectomy, distal pancreatectomy, splenectomy, and D2 lymph node dissection were performed. Pathological examination showed a SCC invasion to the spleen, and normal gastric mucosa between the esophagus and SCC of the stomach. Based on the pathological TNM classification, the tumors were T4N1M0 (Stage IIIB) for the SCC and T1N0M0 (Stage IA) for the adenocarcinoma of the stomach. The patient received adjuvant chemotherapy with S-1, and was recurrence free at 9 months after the surgery.

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.

Pancreatic regeneration: basic research and gene regulation.

Pancreatic regeneration (PR) is an interesting phenomenon that could provide clues as to how the control of diabetes mellitus might be achieved. Due to the different regenerative abilities of the pancreas and liver, the molecular mechanism responsible for PR is largely unknown. In this review, we describe five representative murine models of PR and thirteen humoral mitogens that stimulate ß-cell proliferation. We also describe pancreatic ontogenesis, including the molecular transcriptional differences between α-cells and ß-cells. Furthermore, we review 14 murine models which carry defects in genes related to key transcription factors for pancreatic ontogenesis to gain further insight into pancreatic development.

Surgical and oncological impact of main pancreatic duct spread in invasive ductal adenocarcinoma: A clinicopathological study of 184 resected cases.

BACKGROUND/OBJECTIVES: This study examined main pancreatic ductal spread in invasive ductal adenocarcinoma (IDC) of the pancreas. METHODS: Data from IDC patients who underwent radical surgery from 1990 to 2013 in our hospital were examined retrospectively. Incidence of intraductal spread of pancreatic cancer (IS), distance from the tumor edge, direction of IS and clinicopathological factors associated with the presence of IS were retrospectively examined with data from IDC patients who underwent radical surgery. RESULTS: Among 260 IDC patients who underwent surgery, 184 eligible cases, IS was identified in 42 patients (22.8%) and mean length of IS was 18.7 ± 21.6 mm. Mean distances on the ampullary and distal sides of IS were 11.1 mm and 11.6 mm. IS was significantly more frequent in localized tumors (UICC T1-2 vs. 3-4, p = 0.007), with tumor diameter ≤2 cm (p = 0.034) and in cases with scarce microscopic perineural invasion (p = 0.047). Among patients who underwent pancreaticoduodenectomy and distal pancreatectomy, IS presence (11.6 vs. 21.8%), mean distance to the contralateral side (11.4 vs. 11.6 mm), and IS ≥ 2 cm (3.3 vs. 4.7%) showed no significant differences. Overall survival did not differ significantly between IS-positive and -negative patients in the full analysis set or propensity score-matched patients (42 matched pairs). CONCLUSIONS: In setting resectional margins at 2 cm, a small proportion of cases (3.8%) showed positive surgical margins. Localized tumor (UICC: T1-2, or <2 cm in diameter) requires more care with surgical margins, warranting intraoperative frozen sections.

Impact of aging on morbidity and mortality after liver resection: a systematic review and meta-analysis.

Surgery involving elderly patients is becoming increasingly common due to the rapid aging of societies all over the world. The objective of this study was to elucidate the prognostic differences between elderly and young patients who undergo liver resection. A systematic review based on the PRISMA flow diagram was conducted. Ovid Medline and PubMed were used to search for relevant literature published between January 2000 and March 2013, and the modified MINORS score was used to assess the methodological quality. In cases of hepatocellular carcinoma and miscellaneous liver tumors, the morbidity and mortality rate did not differ significantly between the elderly and young patients. For patients with colorectal metastatic liver cancer, the mortality of the young patients was 2.7 times lower than that of elderly patients. Our review of high-quality retrospective studies was able to elucidate the clinical risks of age on the outcomes after liver surgery in specific patient populations.

Clinical feasibility of laparoscopic lateral pelvic lymph node dissection following total mesorectal excision for advanced rectal cancer.

PURPOSE: To evaluate the technical feasibility, safety and oncological outcomes of laparoscopic lateral pelvic lymph node dissection in patients with advanced low rectal cancer. METHODS: Laparoscopic lateral pelvic lymph node dissection was performed in 18 patients from November 2009 to September 2012. The data regarding the patient demographics, surgical outcomes and short-term oncological outcomes were analyzed. RESULTS: In all 18 patients, the procedures were completed without conversion to open surgery. The mean length of the operation was 603.7 min (473-746 min). The mean number of harvested lateral pelvic lymph nodes was 16.9 (7-27), and five patients (27.8 %) had lymph node metastases. The postoperative mortality and morbidity rates were 0 and 16.7 %, respectively. Three patients developed Grade 2 urinary retention. No local recurrence had developed after a mean follow-up period of 23.6 months. CONCLUSION: Laparoscopic lateral pelvic lymph node dissection is technically feasible, safe and oncologically acceptable within the limitations of the short-term follow-up period.

Preoperative liver function assessments to estimate the prognosis and safety of liver resections.

Liver function assessment is important to ensure safe surgical procedures in patients with hepatocellular disease. Because the liver influences a wide variety of functions, including protein synthesis and metabolic, immune and storage functions, no single parameter is sufficient to adequately address all of these functions. We reviewed the relevant literature concerning the scoring systems, functional tests, plasma parameters and imaging modalities currently used to evaluate the liver function in an attempt to determine which parameters provide the most comprehensive and useful results. While the Child-Pugh scoring system is the gold standard for liver disease assessment, the liver damage grading system recommended by the Liver Cancer Study Group of Japan is also useful. Various models for end-stage liver disease scoring are used for organ allocation. While the indocyanine green clearance test is widely accepted throughout the world, other assessments have not been used routinely for clinical evaluations. The levels of plasma proteins, including albumin, prealbumin, retinol binding protein, apolipoprotein, coagulation factors and antithrombin III, represent the liver productivity. Liver fibrotic markers also correlate with liver function. Imaging modalities such as (99m)Tc-galactosyl serum albumin scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy.

Prognosis and predictors of surgical complications in hepatocellular carcinoma patients with or without cirrhosis after hepatectomy.

BACKGROUND: Although poor liver function is associated with a high morbidity rate and poor prognosis in hepatocellular carcinoma (HCC) patients, the exact effects of liver pathology on the surgical outcomes of HCC patients are poorly understood. The purpose of this study was to assess how the liver pathology of HCC patients affects their prognosis and complications rate after liver resection. METHODS: Between January 2006 and November 2010, 149 consecutive hepatocellular carcinoma patients, including 79 noncirrhosis patients and 70 cirrhosis patients, were enrolled in this study. RESULTS: Among the noncirrhotic patients, operative time, fresh frozen plasma (FFP) transfusion requirement, tumor size, and serum retinol binding protein (RBP) levels were significantly higher in the complications group than in the complications-free groups. On the other hand, in the cirrhotic patients the prothrombin time (PT) and indocyanine green retention value at 15 min (ICGR15) of the complications group were significantly lower and higher, respectively, than those of the complications-free group. In the noncirrhotic patients, recurrence-free survival and overall survival did not differ between the complications and complications-free groups. On the other hand, in the cirrhotic patients, the recurrence-free survival and overall survival of the complications-free group were significantly longer than those of the complications group. CONCLUSIONS: In the noncirrhotic patients, surgical complications had no prognostic effect, whereas they had a significant survival impact in the cirrhotic patients. The surgical strategy for HCC should be based on the patient's pathological background.

Pancreaticoduodenectomy for biliary tract carcinoma with situs inversus totalis: difficulties and technical notes based on two cases.

Situs inversus totalis (SIT) denotes complete right-left inversion of the thoracic and abdominal viscera. Diagnosis and surgical procedures for abdominal pathology in patients with SIT are technically more complicated because of mirror-image transposition of the visceral organs. Moreover, SIT is commonly associated with cardiovascular and hepatobiliary malformations, which make hepatobiliary-pancreatic surgery difficult. Two cases of pancreaticoduodenectomy for biliary tract carcinoma in patients with SIT are presented. Both patients had an anomaly of the hepatic artery. Advanced diagnostic imaging techniques were very important for careful preoperative planning and to prevent misunderstanding of the arrangement of the abdominal viscera. This facilitated the surgical team's adaptation to the mirror image of the standard procedure and helped avoid intraoperative complications due to cardiovascular and hepatobiliary malformations associated with SIT. Pancreaticoduodenectomy in patients with SIT can be performed successfully with detailed preoperative assessment, use of effective techniques by the surgeon, and appropriate support by assistants.

Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients.

BACKGROUND/AIMS: Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). METHODOLOGY: Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. RESULTS: All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. CONCLUSIONS: The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.

Delayed visceral bleeding from liver injury after cardiopulmonary resuscitation.

BACKGROUND: Visceral injury is a life-threatening complication of cardiopulmonary resuscitation (CPR); however, the clinical significance has been masked by the lethal outcome of out-of-hospital cardiac arrest (OHCA). OBJECTIVE: The objective is to share our experience of successful treatment of OHCA patients with serious, CPR-related visceral complications. CASE REPORTS: We report two cases of cardiac-origin OHCA with liver injury exacerbated by heparinization during mechanical circulatory support. Although both patients presented with delayed massive liver bleeding (intrahepatic or peritoneal) that compromised hemodynamic status, one patient was successfully treated by selective transcatheter arterial embolization and the other by a surgical procedure. CONCLUSION: Preventive measures such as careful CPR, as well as interventional or surgical repair after the early diagnosis of visceral injury, are required to improve the outcome in some cases of OHCA.

Current standard values of health utility scores for evaluating cost-effectiveness in liver disease: A meta-analysis.

BACKGROUND: Health utility assessments have been developed for various conditions, including chronic liver disease. Health utility scores are required for socio-economic evaluations, which can aid the distribution of national budgets. However, the standard health utility assessment scores for specific health conditions are largely unknown. AIM: To summarize the health utility scores, including the EuroQOL 5-dimensions 5-levels (EQ-5D-5L), EuroQol-visual analogue scale, short from-36 (SF-36), RAND-36, and Health Utilities Index (HUI)-Mark2/Mark3 scores, for the normal population and chronic liver disease patients. METHODS: A systematic literature search of PubMed and MEDLINE, including the Cochrane Library, was performed. Meta-analysis was performed using the RevMan software. Multiple means and standard deviations were combined using the StatsToDo online web program. RESULTS: The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C. HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients. CONCLUSION: The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.

Laparoscopic hepatectomy: a systematic review, meta-analysis, and power analysis.

PURPOSE: A previous meta-analysis study demonstrated that bleeding and the duration of the hospital stay following laparoscopic hepatectomy (Lap) were significantly smaller and shorter, respectively, than for patients undergoing an open approach (Op). The aim of the present study was to re-evaluate perioperative variables and adverse outcomes in patients undergoing Lap versus (vs) Op after 2000. METHODS: A PubMed and Ovid Medline search identified clinical studies that compared the outcomes of Lap vs Op patients after 2000. A meta-analysis and power analysis were performed. RESULTS: Operative time was not significantly different between the two approaches (95% confidence interval [CI]: -0.063 to 0.992). Patient bleeding in the Lap group was significantly lower than in the Op group (95% CI: -1.027 to -0.390). Complications with Lap patients were significantly less frequent (95% CI: 0.231-0.642), and the duration of the hospital stay for Lap patients was significantly shorter (95% CI: -0.950 to -0.530) than for Op patients. Only one paper presented 80% power with 0.05 α-errors in all four outcomes, whereas four studies did not have sufficient statistical power. CONCLUSIONS: The clinical benefits of Lap include a smaller incidence of complications and a shorter duration of hospital stay at the current time. Several studies had too few cases to sufficiently evaluate these factors, although other studies were appropriately analyzed.

A case of severe acute pancreatitis and ischemic gastropathy caused by acute aortic dissection.

A 49-year-old man presented with chest pain and was given a diagnosis of aortic dissection based on computed tomography (CT) findings. Two days later the dissection reached the origin of the celiac artery and there was poor blood flow from the body to the tail of the pancreas and fundus of the stomach wall. Severe acute pancreatitis developed. Endoscopy showed a near-circumferential gastric ulcer in the gastric cardia and we diagnosed ischemic gastropathy. A fistula between the area of infected pancreatic necrosis and the stomach had formed spontaneously and the necrotic tissue was draining into the stomach. His recovery was uneventful.

[Present status and future prospects of nutritional support teams].

Academic interest in nutritional support teams (NSTs) has increased rapidly in Japan since 1999, when they were first planned by the Japanese Society for Parenteral and Enteral Nutrition (JSPEN). The JSPEN promoted their use extensively after 2006 when extra medical fees were approved for medical management by NSTs under the national health insurance system. The purpose of NSTs is to provide the best nutritional support to patients who are malnourished or at high risk of developing malnutrition, without causing conflict among different medical staff. NSTs offer appropriate medical support and help prevent the deterioration of patients' health. The teams are comprised of specialized medical staff with nutritional expertise who work at the bedside and are committed to establishing good medical practice. The main targets of NSTs are patients who undergo surgery or are being treated in a geriatric or internal medicine unit, including those with lifestyle-related diseases. Therefore, most targets of NSTs are patients with common conditions. A package medical system based on the diagnostic-procedure combination was established, and regional medical centers were integrated to ensure high-quality medical care throughout Japan. Under this system, NSTs are expected to resolve individual patients' dietary issues. In addition, improvement of medical care quality and the training of reliable medical staff are necessary to provide nutritional management in the clinical setting. It will be necessary to the revise the assessment of NSTs as proposed by a committee of the Japanese Nutritional Support Promotion Group or to carry out surveillance to evaluate the outcomes of NST activity.

Impaired liver regeneration with humoral and genetic disturbances in urinary trypsin inhibitor-deficient mice.

BACKGROUND/AIMS: Urinary trypsin inhibitor (UTI) is an innate anti-inflammatory regulator. It can block the release of inflammatory factors, prevent the cascade reaction of cytokines and inhibit excessive activation of leukocytes. Liver regeneration (LR) is a dynamic molecular phenomenon without inflammation. Many cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), have been implicated in regulating LR. However, the role of UTI in LR is totally unknown. The aim of this study was to elucidate the role of UTI in LR using genetically UTI-deficient mice. METHODS: We performed 68% hepatectomy, comparing UTI (-/-) and UTI (+/+) mice. Recovery of liver weight was recorded and we calculated labelling indices after 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. A DNA microarray was used to examine gene expression followed by real-time polymerase chain reaction. Serum IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) were measured. RESULTS: LR in UTI (-/-) mice was delayed at 36 h after hepatectomy, at which time the DNA profile was different. One hundred and fourteen genes were upregulated and 100 genes were downregulated in UTI (-/-) mice at 36 h after hepatectomy among the 21, 977 mRNAs examined. Furthermore, serum IL-6, IL-10, MCP-1 and MIP-1beta levels at 36 h after hepatectomy in the UTI (-/-) mice were significantly higher than in the UTI (+/+) mice. CONCLUSION: UTI appears to important cytokine and chemokine regulation in normal liver regeneration.

Clinical compliance with an oral uracil/tegafur (UFT) plus leucovorin (LV) regimen as adjuvant chemotherapy in Japanese colorectal cancer patients.

BACKGROUND: The combination of oral uracil/tegafur (UFT) plus leucovorin (LV) is widely accepted as adjuvant chemotherapy for stages II and III of colorectal cancer. However, the clinical compliance of Japanese patients with this regimen has not been clearly elucidated to date. METHODS: A total of 40 Japanese outpatients were treated with oral UFT plus LV as adjuvant chemotherapy following colorectal cancer surgery between January 2005 and June 2007. UFT capsules (300-500 mg/body per day) and LV tablets (75 mg/body per day, administered with each dose of UFT) were to be taken for 28 days, followed by 7 days of rest, with this cycle repeated every 35 days for 6 months or until recurrence. The patients were classified into the following three groups based on compliance: the completed group (n = 21), the modified group (n = 12), and the discontinued group (n = 7). RESULTS: The UFT doses (mean +/- SD) were 267 +/- 35 mg/m(2) in the completed group, 276 +/- 50 mg/m(2) in the modified group, and 288 +/- 22 mg/m(2) in the discontinued group. The UFT dose in the discontinued group tended to be higher than that in the completed group (P = 0.12). The most frequent symptoms of nonhematologic toxicity were appetite loss (45%) and fatigue (45%). There were no hematologic or nonhematologic toxicities of grade 3 or 4. CONCLUSION: The regimen of oral UFT plus LV produced only low-grade toxicity and was convenient for outpatients. It appears that the initial UFT dose might be associated with the development of toxicity in the oral UFT plus LV regimen.

Effects of a low-fat meal on the oral bioavailability of UFT and leucovorin in patients with colorectal cancer.

BACKGROUND: UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 x 100-mg capsules; dose in terms of tegafur) and leucovorin (1 x 25-mg tablet). METHODS: Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin). RESULTS: For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect. CONCLUSION: A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal.

Rapid recovery of postoperative liver function after major hepatectomy using saline-linked electric cautery.

BACKGROUND/AIMS: The exact effect of heat injury in the residual liver on postoperative liver function is not totally understood. The purpose of this study was to compare postoperative liver function after major liver resection using an argon laser beam coagulator (AR) and that using saline-linked electric cautery (SLC) for vessels and bile duct sealing. METHODOLOGY: Between January 2001 and December 2005, thirty patients were analyzed in this study retrospectively. The inclusion criteria were that the patients received hemihepatectomy without vascular and biliary reconstruction in a non-cirrhotic liver. Operative variables and liver functions were compared between the AR method and the SLC method. RESULTS: The clinical profiles of the two groups were almost identical, including preoperative hepatic function. Although there was no difference in most of the intraoperative variables between them, warm ischemic time in the SLC group was shorter than in the AR group (46.53 + 25.42 min vs. 70.47 +/- 11.48 min: p=0.003). Albumin and bilirubin levels at 7 days after hepatectomy were not significantly different between the two groups, but low-density lipoprotein (LDL) and apolipoprotein B (ApoB) levels in the SLC group at 7 days after hepatectomy were significantly higher than in the AR group (84.27 +/- 14.38 mg/dl vs. 60.21 +/- 14.27 mg/dl: p=0.001; 69.53 +/- 17.18 mg/dl vs. 55.87 +/- 9.56 mg/dl: p=0.012, respectively). CONCLUSION: SLC reduces warm ischemic time during hepatectomy. Furthermore, the rapid recovery of LDL and ApoB levels in the SLC group indicates that the SLC method has potential benefits for postoperative hepatic function.

Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy.

BACKGROUND AND OBJECTIVES: Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. METHODS: Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection. RESULTS: In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment. CONCLUSION: aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.