Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Global numerical simulation of fluid-structure-acoustic interaction in a single-reed instrument.

A numerical simulation of a single-reed instrument with a pressure chamber is conducted to examine the interaction among the flow, reed oscillation, and acoustic propagation. The flow and acoustic fields are predicted using the three-dimensional compressible Navier-Stokes equations, whereas the one-dimensional dynamic beam equation is solved for reed oscillation. The deforming geometry in the aeroacoustic field is expressed by the volume penalization method as an immersed boundary technique. The results showed that the waveforms of the tip opening and far-field acoustic spectra agreed well with those measured experimentally. The three-dimensional flow configuration near the tip opening was visualized, and the measurement of the instantaneous volume flow rate at the tip opening revealed that 30%-40% of the total flow rate passed through the side opening. The spectral tendencies of the time derivatives of the flow rate for different tip openings were consistent with that of the far-field sound, indicating that the slope of the flow rate waveform significantly affects the generated sound's harmonics.

[Two Cases of Long-Term Use of TAS-102 for Unresectable Colorectal Cancer].

TAS-102 has been administered to patients with unresectable colorectal cancer. We initiated TAS-102 administration in 2014 and gradually increased the number of indications. In a global, multicenter, randomized, double-blind, phase III study (RECOURSE study), TAS-102 administration improved overall survival by 1.8 months and progression-free survival by 0.3 months compared with those in the placebo group. However, there are limited clinical reports of long-term administration of TAS-102. We encountered 2 cases of continuous long-term use of the TAS-102 for over 2 years. In our cases, although the cancer had been recognized early as exhibiting slow growth during follow-up, the physical symptoms did not appear for an extended period. Although grade 3 neutropenia was pointed out several times during the follow-up term, severe digestive symptoms had not occurred. Therefore, the patients could remain motivated to receive the drug. In our cases, the adequate treatment for neutropenia enabled long-term administration of TAS-102; therefore, TAS-102 would be tolerable for patients of colorectal cancer after receiving chemotherapy for an extended period.

Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102).

Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg-1 , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%) and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer.

Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101).

BACKGROUND: Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features. METHODS: HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined. RESULTS: From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity. CONCLUSIONS: HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression.

Comparison between anatomical subsegmentectomy and nonanatomical partial resection for hepatocellular carcinoma located within a single subsegment: a single-center retrospective analysis.

BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy. METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28). RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008). CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.

Direct numerical simulation of fluid-acoustic interactions in a recorder with tone holes.

To clarify fluid-acoustic interactions in an actual recorder with opened and closed tone holes, flow and acoustic fields were directly numerically simulated on the basis of the compressible Navier-Stokes equations. To validate the simulation accuracy, the flow field around the windway and sound pressure above the window were measured. The predicted acoustic fields clarify changes of the positions of pressure nodes and anti-nodes in accordance with the state of the tone holes and the Mach number of the jet velocity. The fundamental mechanism of the self-sustained oscillations in a three-dimensional actual recorder is visualized by the predicted acoustic and flow fields. This result is also consistent with the relationship between the jet behaviors and pressure fluctuations based on the jet-drive model. Moreover, the effects of the fine vortices in the jet, which appear at the high Mach number of jet velocity of 0.099, on the sound are discussed. The time difference between the generation of the disturbances and the most intense deflection of the jet is identified and compared with the time delay of acoustic reflection around the window.

The preventive surgical site infection bundle in patients with colorectal perforation.

BACKGROUND: Incisional surgical site infection (SSI) is one of the most frequent complications that occur after colorectal surgery. Surgery for colorectal perforation carries an especially high risk of incisional SSI because fecal ascites contaminates the incision intraoperatively, and in patients who underwent stoma creation, the incision is located near the infective origin and is subject to infection postoperatively. Although effectiveness of the preventive SSI bundle of elective colorectal surgery has been reported, no study has focused exclusively on emergency surgery for colorectal perforation. METHODS: Patients with colorectal perforation who underwent emergency surgery and stoma creation from 2010 to 2015 at our center were consecutively enrolled in the study. In March 2013, we developed the preventive incisional SSI bundle for patients with colorectal perforation undergoing stoma creation. The effectiveness of the bundle in these patients was determined and the rates of incisional SSI between before and after March 2013 were compared. RESULTS: We enrolled 108 patients with colorectal perforation who underwent emergency operation during the study period. Thirteen patients were excluded because they died within 30 days after surgery, and 23 patients without stoma were excluded; thus, 72 patients were analyzed. There were 47 patients in the pre-implementation group and 25 patients in the post-implementation group. The rate of incisional SSI was significantly lower after implementation of preventive incisional SSI bundle (43% vs. 20%, p = 0.049). Postoperative hospital stay was significantly shorter after implementation of the bundle (27 vs. 18 days respectively; p = 0.008). CONCLUSIONS: The preventive incisional SSI bundle was effective in preventing incisional SSI in patients with colorectal perforation undergoing emergency surgery with stoma creation.

[A case of jejunal ectopic pancreatic cancer: the diagnostic usefulness of MRI].

A 70-year-old man was referred to our hospital because of elevated CA19-9. Magnetic resonance imaging revealed a jejunal tumor having duct and retention cyst-like structures, which suggested ectopic pancreatic cancer. We resected that part of the jejunum and the lymph nodes around the tumor. Pathological examination revealed an adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Adjuvant chemotherapy with gemcitabine was performed for half a year. After 8 months, CA19-9 remained elevated, and liver metastasis occurred. We began treatment with tegafur/gimeracil/oteracil potassium (S-1) and particle beam therapy. After 7 months, CA19-9 was normal, and the patient has remained in partial remission with S-1 treatment. Ectopic pancreas tissues typically occur in the stomach and duodenum and rarely become cancerous. Here, we report the features of a rare and illustrative case of jejunal ectopic pancreatic cancer.

[A case of mixed adenoneuroendocrine carcinoma of the transverse colon].

A 7 1-year-old man presented to our hospital with constipation and abdominal pain. Computed tomography of the abdomen and colonoscopy revealed advanced cancer of the transverse colon. The biopsy specimen indicated a highly differentiated adenocarcinoma. The patient underwent extended right hemicolectomy with regional lymph node dissection. Pathological examination showed a neuroendocrine carcinoma (NEC) with concurrent adenocarcinoma of the transverse colon and regional lymph node metastases of the NEC and adenocarcinoma. The histopathological examination confirmed a diagnosis of mixed adenoneuroendocrine carcinoma (MANEC) in accordance with the 2010 WHO Classification of Tumors of the Digestive System. Liver and lung metastases were identified 8 months after the surgery. We administered chemotherapy including 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX) plus bevacizumab, with limited therapeutic effect, as the disease progressed despite treatment. The patient chose best supportive care 13 months after the surgery. Several studies have reported that most patients with adenoendocrine cell carcinoma, including MANEC, experience relapse within 1 year after surgery, and few patients remain disease-free for long periods after surgery. The optimal strategy for the management of MANEC is variable owing to its rarity; only 2 cases of MANEC in the colon, including the present case, have been reported in Japan. It is thus important to gather more evidence on this disease and its management.

The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.

BACKGROUND: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. METHODS: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. DISCUSSION: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. TRIAL REGISTRATION: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

Activation of the aryl hydrocarbon receptor induces hepatic steatosis via the upregulation of fatty acid transport.

The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix/Per-ARNT-Sim domain transcription factor, which is activated by various xenobiotic ligands. AHR is known to be abundant in liver tissue and to be associated with hepatic steatosis. However, it has not yet been elucidated how the activation of AHR promotes hepatic steatosis. The aim of this study is to clarify the role of AHR in hepatic steatosis. The intraperitoneal injection of 3-methylcholanthrene (3MC), a potent AHR ligand, into C57BL/6J mice significantly increased the levels of triglycerides and six long-chain monounsaturated fatty acids in the livers of mice, resulting in hepatic microvesicular steatosis. 3MC significantly enhanced the expression level of fatty acid translocase (FAT), a factor regulating the uptake of long-chain fatty acids into hepatocytes, in the liver. In an in vitro experiment using human hepatoma HepG2 cells, 3MC increased the expression level of FAT, and the downregulation of AHR by AHR siRNA led to the suppression of 3MC-induced FAT expression. In addition, the mRNA level of peroxisome proliferator-activated receptor (PPAR) α, an upstream factor of FAT, was increased in the livers of 3MC-treated mice. Taking together, AHR activation induces hepatic microvesicular steatosis by increasing the expression level of FAT.

Laparoscopic surgery for synchronous gastric and colorectal cancer: a preliminary experience.

BACKGROUND: Increasingly, laparoscopy-assisted gastrectomy and laparoscopy-assisted colorectal surgery are being performed. However, simultaneous laparoscopic surgery for synchronous gastric and colorectal cancer is rare and its feasibility unknown. METHOD: Early surgical outcomes, including operation time, intraoperative bleeding, postoperative morbidity, mortality, and the duration of the postoperative hospital stay, were investigated in seven consecutive patients who underwent simultaneous laparoscopy-assisted gastrectomy and colorectal surgery at the Cancer Institute Hospital between 2005 and 2008 to clarify the feasibility of simultaneous laparoscopic surgery. RESULTS: Mean operation time was 392 min and estimated blood loss was 90 mg in patients undergoing simultaneous laparoscopic surgery. Although postoperative morbidity was observed in three patients (surgical site infection, gastric fullness, and enteritis), they recovered well, and the duration of postoperative hospital stay was 19.6 +/- 14.1 days. There was no postoperative mortality. Intraoperative complication which required conversion to open surgery was also not found in any of the patients. A small incision measuring 5-6 cm in length was sufficient for both retrieval of resected specimen and enteric anastomosis in all patients. CONCLUSIONS: The laparoscopic approach is a feasible procedure for synchronous gastric and colorectal cancer, provided that the operation is performed by experienced surgeons.

Long-term outcomes of incidental gallbladder carcinoma without additional resection: A single institution experiment.

Incidental gallbladder carcinoma (IGC), defined as unexpected malignancy identified in the surgical gallbladder specimen of a cholecystectomy performed for a benign diagnosis, can be difficult to suspect preoperatively. Furthermore, there are valid clinical reasons to defer reoperation for additional resection, particularly in elderly patients. The present study aimed to determine the long-term outcomes and prognostic factors associated with recurrence in patients with IGC. The medical records of 678 patients who underwent cholecystectomy at Toyooka Hospital between September 2011 and November 2017 were reviewed. The cases identified to be IGC were retrospectively analyzed to determine patient and histopathological characteristics, surgical details, long-term outcomes and factors associated with cancer recurrence. A total of 22 patients were diagnosed with gallbladder carcinoma following cholecystectomy by histopathological examination, and 12 of these were identified to be IGC. The median age was 80 years (range 70-89 years). Although 6 of the 12 patients with IGC had stage pT2 or pT3 tumors, only 1 patient underwent additional resection. Recurrence occurred in 3 of the 8 patients who did not undergo additional resection and were available for long-term follow-up. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Recurrence was not associated with the extent of tumor invasion but may be associated with other histopathological findings, preoperative treatment history, and risk factors for recurrence. Furthermore, long-term survival was observed in patients with pT2 and pT3 tumors who did not undergo additional resection. Even if it is a progressive IGC case, appropriate preoperative treatment or cholecystectomy without persistence of the carcinoma cell, based on a preoperative image evaluation and a postoperative histopathological examination, may greatly influence the long-term prognosis of IGC.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer.

AIM: Neoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established. METHODS: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and S-1/cisplatin/docetaxel(DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous-type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48-1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43-1.22). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS. CONCLUSIONS: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer.

Quality control and educational value of laparoscopy-assisted gastrectomy in a high-volume center.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is increasingly performed in Japan by a number of surgeons. As this is a relatively new technique, a training system is important, however there has been little discussion about an educational system for teaching trainees to perform LAG and the ideal training system has not yet been established. PATIENTS AND METHODS: Two hundred and sixty-three patients who underwent LAG at the Cancer Institute Hospital were included in this study. In all cases there was standardization of LAG (the way in which the surgical field was formed by the assistant and the way the operator dissected the lymph nodes was determined and all cases were performed using the same laparoscopic procedures) and a step-by-step training system was completed. Specialists performed the surgery in 213 patients (S group) while the remaining 50 patients had their surgery performed by trainees (T group). Early surgical outcomes were compared between specialists and trainees to clarify whether the standardization and our educational system are useful in maintaining the quality of LAG. RESULTS: T-group patients had significantly longer operation times than those of S-group (262.3 +/- 7.3 versus 233.3 +/- 3.7 min), however, the trainees reached the plateau of their learning curve earlier than previously reported. All other early surgical outcomes examined, including intraoperative blood loss (76.7 +/- 35.1 versus 64.9 +/- 7.7 ml), number of retrieved lymph nodes (33.4 +/- 1.4 versus 35.7 +/- 0.8), morbidity (8 versus 14%), and mortality (0% in both groups), were not significantly different between the two groups. CONCLUSION: The surgical results of T-group were almost equal to those of S-group, showing that our educational system is effective and surgical quality is maintained. Standardized laparoscopic procedures and sufficient intensive experience in the short term are requisites for effectively learning how to perform LAG.

Effects of reconstruction methods on a patient's quality of life after a proximal gastrectomy: subjective symptoms evaluation using questionnaire survey.

BACKGROUND AND AIMS: Proximal gastrectomy is typically indicated in early gastric cancer of the upper third of the stomach. Esophagogastrostomy (EG) and jejunum interposition (JI) are often selected as reconstruction methods, although the more appropriate method of the two is unknown. MATERIALS AND METHODS: One hundred and seven patients, who underwent a proximal gastrectomy followed by either an EG or a JI, were sent a questionnaire of 33 questions about subjective symptoms. Eighty-three patients (45 in the JI group and 38 in the EG group) returned the questionnaire. Results were compared between the two groups to identify the appropriate reconstruction method after a proximal gastrectomy. Also, changes in a patient's body weight after surgery were compared. RESULTS: Early and late dumping syndromes and gastroesophageal reflux associated symptoms were equally observed between the two groups. However, abdominal discomfort after meals (P = 0.008), continuous gastric fullness (P = 0.028), and hiccups between meals (P = 0.022) were often observed in the JI group. The loss of body weight was not significantly different between the two groups. CONCLUSION: EG is a better reconstruction method compared to a JI after a proximal gastrectomy when evaluating subjective symptoms. Prospective study is warranted to clarify the better reconstruction method following proximal gastrectomy in terms of both subjective and objective symptoms.

Anti-tumor effect of pegylated interferon in the rat hepatocarcinogenesis model.

Interferon (IFN) is a multifunctional cytokine which works as a suppressor of hepatocarcinogenesis. Pegylated interferon (PEG-IFN) is a modified form of IFN with different pharmacokinetics. We evaluated the anti-tumor effect of PEG-IFN using a rat hepatocarcinogenesis model. Male Fisher Rats were treated using the Solt and Faber model to induce liver cancer. IFN and PEG-IFN were administered from chemical initiation, and pre-neoplastic foci and neoplastic hepatocellular carcinoma (HCC) were examined at 4 and 40 weeks after chemical initiation, respectively. Apoptosis-related molecules such as p53 and Fas-L, proliferating cell nuclear antigen (PCNA), and oxidative stress-related molecules such as 8-hydroxydeoxyguanosine (8-OHdG) and thioredoxin (TRX) were assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of Notch-1, a molecule related to the regenerative and oncogenic processes was also examined. The generation of foci and HCC were significantly suppressed in IFN and PEG-IFN groups compared with the control group. Whereas PCNA and Notch-1 were strongly expressed in the foci and HCC, Fas-L was mainly detected in the surrounding hepatocytes. 8-OHdG and TRX were also detected in the foci. Although PCNA and Notch-1 were down-regulated in IFN- and PEG-IFN-treated groups, Fas-L was up-regulated in those groups. The activation of Notch-1 signaling and the accumulation of oxidative stress in the pre-neoplastic foci might be associated with the progression of HCC in the DEN-induced hepatocarcinogenesis model. The inhibitory effect of the PEG-IFN and IFN on hepatocarcinogenesis was almost the same, and this might be induced by the Fas-related apoptosis in the surrounding tissues.