Background: In the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic stellate cell (HSC) differentiation and a novel subpopulation of HSCs which express CD133 and exhibit properties of progenitor cells has been described in rats. The carbon tetrachloride (CCl₄)-induced mouse model has been historically relied upon to study liver injury and regeneration. We exposed mice to CCl₄to assess whether EGF and CD133+ HSCs are up-regulated in chronically injured liver.Methods: CCl₄in olive oil was administered to strain A/J mice three times per week by oral gavage.Results: Multiple well-differentiated HCCs were found in all livers after 15 weeks of CCl₄treatment. Notably, HCCs developed within the setting of fibrosis and not cirrhosis. CD133 was dramatically up-regulated after CCl₄treatment, and increased expression of desmin and glial fibrillary acidic protein, representative markers of HSCs, was also observed. EGF expression significantly decreased, contrary to observations in humans, whereas the expression of amphiregulin, another EGFR ligand, was significantly increased.Conclusions: Species-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease. CCl₄-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC.

Objective: This randomized phase II/III study evaluated the superiority of neoadjuvant therapy with gemcitabine plus S-1 over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Background: PDAC is a leading cause of cancer mortality that urgently requires better treatment. Methods: Patients with resectable PDAC (without arterial abutment) were randomly assigned to upfront surgery or neoadjuvant chemotherapy with gemcitabine (1000 mg/m ² days 1 and 8) and S-1 (40–60 mg orally twice daily, days 1–14 every 3 wk for 2 cycles). Phase II and III primary endpoints were resection rate and overall survival, respectively. UMIN Clinical Trials Registry number: UMIN000009634. Results: Patients (n=364) were enrolled and randomly allocated to upfront surgery (UPS; n=182) or neoadjuvant gemcitabine plus S-1 (NAC-GS; n=182). Patient demographics and tumor characteristics were balanced between groups. Median overall survival in the UPS and NAC-GS groups was 26.6 (95% CI: 21.5, 31.5) and 37.0 (95% CI: 28.6, 43.3) months, respectively. The hazard ratio for mortality in the NAC-GS group compared with the UPS group was 0.73 (95% CI: 0.56, 0.95; P =0.018). Median relapse-free survival in the UPS and NAC-GS groups was 11.3 (95% CI: 9.41, 13.5) and 14.3 (95% CI: 11.7, 17.0) months, respectively. The hazard ratio for relapse in the NAC-GS group compared with the UPS group was 0.77 (95% CI: 0.61, 0.98; P =0.030). Conclusions: The Prep-02/JSAP05 trial results showed that neoadjuvant chemotherapy with gemcitabine plus S-1 significantly extends survival compared with upfront surgery in patients with resectable PDAC.

In 2023, the Japan Pancreas Society (JPS) published the new eighth edition of the Japanese classification of pancreatic carcinoma. We present here an excerpted version in English, based on the latest edition. The major changes in this revision are as follows: In the eighth edition of the Union for International Cancer Control (UICC), the T category was changed to be based on tumor size; however, the eighth edition of the Japanese classification retains the previous T category based on local invasion factors. Lymph nodes have been renamed, and regional lymph nodes have been defined by location. Peritoneal cytology, which was not previously included in distant metastasis (M), has now been included in the M category. Moreover, significant additions have been made regarding the pathological diagnosis of endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNAB) and criteria for histological assessment of the effects after chemotherapy and radiation therapy. Although this classification is aimed at carcinoma originating in the pancreas, not in the bile duct or duodenum, if the differentiation of the primary organ is difficult, this classification should be applied. It is also desirable to describe tumors other than carcinoma and metastatic tumors to the pancreas in accordance with this classification.

Objectives: We aimed to clarify the detailed pattern of lymph node (LN) metastasis spread in patients with pancreatic cancer. Methods: This retrospective study enrolled 429 patients who underwent pancreatectomy with extended lymphadenectomy for pancreatic cancer. The prognostic implications of LN metastasis were evaluated, and the position, frequency, and association with other clinicopathologic factors were investigated. Results: Lymph node metastasis was confirmed pathologically in 289 patients (67.4%). The prognosis of patients with LN metastasis was significantly poorer than that of patients without LN metastasis (P < 0.001). Distant LN metastasis occurred frequently, regardless of the tumor site. Patients classified with T1 or T2 only had regional LN metastasis, whereas there was a high rate of distant LN metastasis, including the para-aortic LNs, in patients with T3 or higher-stage tumors. Para-aortic LN metastasis was significantly associated with arterial and perineural invasion (P = 0.006 and P < 0.001, respectively). Lymph node metastasis in the hepatic portal region was a strong predictor of para-aortic LN metastasis in pancreatic head cancer. Conclusions: Pancreatic cancer frequently metastasized to distant LNs via a complex pathway and developed into systemic disease. Aggressive multimodality therapy, including neoadjuvant therapy, is essential to improve the long-term survival of patients at substantial risk of distant LN metastasis.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations. It is urgent that we identify carcinogenesis-related genes to establish an innovative treatment strategy for this disease.