Prognostic Significance of NQO1 Expression in Non-neoplastic Esophageal Squamous Epithelium for Patients With Esophageal Cancer.

BACKGROUND/AIM: NAD(P)H dehydrogenase [quinone] 1 (NQO1), an antioxidant enzyme, confers resistance to anticancer agents. NQO1 C609T is a single-nucleotide polymorphism associated with reduced protein expression in the non-neoplastic esophageal squamous epithelium (ESE). This study aimed to investigate immunohistochemical NQO1 expression in non-neoplastic ESE and to elucidate its prognostic significance in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant therapy followed by esophagectomy. MATERIALS AND METHODS: NQO1 expression in non-neoplastic ESE was determined in surgical specimens from 83 patients with ESCC using immunohistochemistry. The association between NQO1 expression and clinicopathological factors, and the prognostic significance of NQO1 expression for relapse-free survival (RFS) were statistically evaluated. RESULTS: Patients with complete loss or weak NQO1 expression and patients with moderate or strong NQO1 expression were classified into the NQO1-negative (n=29) and NQO1-positive (n=54) groups, respectively. The downstaging of T classification status after neoadjuvant therapy was significantly more frequent in the NQO1-negative group than in the NQO1-positive group (59% vs. 33%; p=0.036). The NQO1-negative group had significantly more favorable RFS than the NQO1-positive group (p=0.035). Multivariate survival analysis demonstrated that NQO1 negative expression had a favorable prognostic impact on RFS (HR=0.332; 95%CI=0.136-0.812; p=0.016). CONCLUSION: Immunohistochemical evaluation of NQO1 expression in non-neoplastic ESE has clinical utility for predicting patient prognosis after neoadjuvant therapy followed by esophagectomy and might be helpful for selecting candidates for adjuvant therapy to treat ESCC.

Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors.

BACKGROUND: Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC. METHODS: One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated. RESULTS: In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023). CONCLUSIONS: Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.

Surgical Outcomes of Ipsilateral Inguinal Hernia After Kidney Transplantation.

OBJECTIVES: We aimed to clarify the clinical features and outcomes of ipsilateral inguinal hernias after kidney transplantation. PATIENTS AND METHODS: Eleven patients diagnosed with inguinal hernia on the ipsilateral side after kidney transplantation between 2011 and 2022 were analyzed. Clinical data were retrospectively reviewed from the medical records. RESULT: Eleven patients were included in the analysis (median age, 68 [range, 28-75] years, male, n = 11). The time from kidney transplantation to hernia surgery was 107 (6-393) months. Eight patients had direct-type inguinal hernias. Three had indirect-type inguinal hernias. Hernia contents included the small intestine (n = 5), transplanted ureter and bladder (n = 2), only bladder (n = 1), transplanted kidney, ureter, and small intestine (n = 1), transplanted kidney and small intestine (n = 1), and transplanted ureter (n = 1). Six patients (55%) were diagnosed with urinary tract obstruction due to inguinal hernia. All hernias were repaired using mesh. The plug method was used in 9 cases. The Lichtenstein method was used in 2 cases. The median operative time was 110 (73-155) minutes, and the median blood loss was 3 (1-85) mL. The median postoperative hospital stay was 4 (2-7) days. In the 6 patients with urinary obstruction, the serum creatinine levels improved (P = .028), and the transplanted urinary tract obstruction disappeared after surgery. There was no recurrence of inguinal hernia. One patient experienced chronic pain in the groin area (Clavien-Dindo grade II) during follow-up. CONCLUSION: Surgical intervention for inguinal hernia after kidney transplantation is safe and effective for preventing worsening of the kidney graft function.

Malignancy After Living Donor Liver Transplantation.

OBJECTIVES: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). PATIENTS AND METHODS: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. RESULTS: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). CONCLUSION: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Mucin phenotype and genetic alterations in non-V600E BRAF-mutated colorectal cancer.

Colorectal cancer (CRC) is a heterogeneous disease that develops through stepwise accumulation of genetic alterations and progresses via several distinct pathways. However, the tumorigenesis of CRCs with BRAF non-V600E mutations remains unclear. Here, we aimed to elucidate the tumorigenesis of CRCs with BRAF non-V600E mutations, focusing on differences in mucin phenotype and genetic alterations between CRCs with non-V600E and V600E mutations. We investigated 201 patients with CRC and performed panel testing of 415 genes to identify BRAF mutations. Patients were classified into five mucin phenotypes - large-intestinal, small-intestinal, gastric, mixed, and unclassified - using immunohistochemistry for CD10, MUC2, MUC5AC, and MUC6. BRAF mutations were identified in 24 of 201 patients' samples, of which 13 (6.5%) had a V600E mutation (V600E-mutant) and 11 (5.5%) had non-V600E mutations (non-V600E-mutant). MUC5AC expression was significantly associated with V600E mutations (P = 0.040), while CD10 expression was significantly associated with non-V600E mutations (P = 0.010). The small-intestinal mucin phenotype was significantly associated with non-V600E mutations (P = 0.031), while the mixed mucin phenotype was significantly associated with V600E mutations (P = 0.027). Regarding genetic alterations, focusing on the WNT signaling pathway, APC mutation was significantly associated with non-V600E mutations (P < 0.001), while RNF43 mutation was significantly associated with V600E mutations (P = 0.020). Considering the differences in mucin phenotype and genetic alterations, different modes of tumorigenesis are assumed for CRC with BRAF V600E mutation and non-V600E mutations. These findings are important in understanding the biology and treatment strategies for BRAF-mutant CRC.

Risk factors for death from other diseases after curative gastrectomy and lymph node dissection for gastric cancer.

BACKGROUND: Recent advances in treatment are expected to bring a cure to more patients with gastric cancer (GC). Focusing on the risk of death from other diseases (DOD) has become a crucial issue in patients cured of GC. The aim of this study was to elucidate the risk factors for DOD in patients who underwent curative gastrectomy with lymph node dissection for GC. METHODS: We enrolled 810 patients who underwent curative gastrectomy with lymph node dissection for GC from January 1990 to December 2014 and had no recurrence or death of GC until December 2019. We investigated the risk factors for DOD defined as death excluding death from a malignant neoplasm, accident, or suicide after gastrectomy, focusing on the perioperative characteristics at gastrectomy. RESULTS: Among 315 deaths from any cause, 210 died from diseases other than malignancy, accidents and suicide. The leading cause of DOD was pneumonia in 54 patients (25.7%). The actual survival period in 167 patients (79.5%) with DOD was shorter than their estimated life expectancy at gastrectomy. Multivariate analysis revealed that a high Charlson Comorbidity Index score (score 1-2: hazard ratio [HR] 2.192, 95% confidence interval [CI] 1.713-2.804, P < 0.001 and score ≥ 3: HR 4.813, 95% CI 3.022-7.668, P < 0.001), total gastrectomy (HR 1.620, 95% CI 1.195-2.197, P = 0.002) and the presence of postoperative complications (HR 1.402, 95% CI 1.024-1.919, P = 0.035) were significant independent risk factors for DOD after gastrectomy for GC, in addition to age of 70 years or higher, performance status of one or higher and body mass index less than 22.0 at gastrectomy. CONCLUSIONS: Pneumonia is a leading cause of DOD after curative gastrectomy and lymph node dissection for GC. Paying attention to comorbidities, minimizing the choice of total gastrectomy and avoiding postoperative complications are essential to maintain the long-term prognosis after gastrectomy.

[Long-Term Survival after Liver and Pulmonary Metastasectomy Following Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma-A Case Report].

The patient was a 61-year-old man with a diagnosis of carcinoma of the pancreatic head. Abdominal computed tomography( CT)showed no distant metastasis, and he underwent subtotal stomach-preserving pancreatoduodenectomy. Immediately after surgery, he received liver perfusion chemotherapy with 5-fluorouracil followed by systemic gemcitabine. Eighteen months after surgery, CT revealed liver metastasis in the S6 segment, and partial hepatectomy was performed. The pathological diagnosis was liver metastasis of pancreatic cancer. Postoperatively, the patient was treated with gemcitabine and S-1 therapy for 1 year and then switched to S-1 monotherapy for about 6 months. Four years after the initial surgery, CT showed 2 metastases in the right lung. After 2 months of S-1 monotherapy, wedge resection of the upper and lower lobes of the right lung was performed. Gemcitabine and nab-paclitaxel therapy were administered, after the metastasectomy, but pleural dissemination appeared on CT 5 years after the initial surgery. Modified FOLFIRINOX therapy was started and continued for 8 months, but CT revealed further disseminated lesions in the diaphragm. Palliative irradiation was provided, but the disease gradually progressed. After multidisciplinary treatment, the patient survived for 6 years and 3 months after the initial surgery.

Axillary cutaneous metastasis of colon cancer with microsatellite instability-high and BRAF V600E mutation treated with curative-intent surgery: a case report.

BACKGROUND: Colorectal cancer (CRC) metastasizes to various organs, while cutaneous metastases are rare. Although there have been several previous reports of axillary cutaneous metastases with other metastases of CRC, there has never been a report of axillary cutaneous metastasis of CRC that could be treated with curative-intent surgery. CASE PRESENTATION: A 68-year-old female was diagnosed with an axillary cutaneous tumor and ascending colon cancer with invasion to the duodenum. Histopathological and immunohistochemical analysis revealed that the axillary cutaneous tumor showed adenocarcinoma and the same expression pattern for cytokeratin 7, cytokeratin 20, and CDX2 as the ascending colon cancer, and that proved to be KRAS-NRAS wild type, MSI-H, and with a BRAF V600E mutation. The patient underwent a two-stage resection with curative intent after receiving neoadjuvant chemotherapy which consisted of one cycle of modified FOLFOX6 followed by two cycles of FOLFOXIRI. During and after the two operations, the patient received a total of nine cycles of modified FOLFOX6 as adjuvant chemotherapy. Two years after the initial surgery, and 1 year and 8 months after the second surgery, the patient is alive without recurrence. CONCLUSIONS: To the best of our knowledge, this is the first report of axillary cutaneous metastasis of CRC with microsatellite instability-high and BRAF V600E mutation that could be treated with curative-intent surgery. It is important to recognize the presence of such cases for the accurate diagnosis and treatment of CRC with cutaneous metastasis.

Longitudinal changes in youth baseball batting based on body rotation and separation.

BACKGROUND: Identifying the characteristics of batting mechanics, such as the proper angle and position of each body segment in youth baseball players, is important for proper instructions. This study aimed to identify the age-related changes in batting kinematics including rotational and separational movements of the head, upper trunk, pelvis, and arms, in youth baseball players. METHODS: Over the three seasons, we measured the batting motion of baseball players aged 6- to 12 years using three high-speed cameras. Participants were divided into six age categories according to the little league eligibility rules (players were classified according to their age as of July 31 of a given year). Toss batting was performed using an automatic tossing machine set obliquely in front of the batter. Additionally, we analyzed the rotation angles of the head, upper trunk, pelvis, and arm direction, and the separation angles-calculated using the difference of each rotational angle and the head movement distance and step width-at five points in batting phase: stance, load, foot contact, pre-swing, and ball contact. Finally, 17 players from under 8 (U8, i.e., approximately 7-8 years) to U10 and 13 from U11 to U13 were analyzed. A one-way repeated measures analysis of variance was performed to analyze age-related changes in batting kinematics. RESULTS: Several age-related changes in batting kinematics at various batting point were observed. The head-to-upper trunk separation angle increased with age from U8 to U10 during the foot contact (effect sizes [ES] = 0.658) and from U11 to U13 during the pre-swing (ES = 0.630). Additionally, the U13 showed a significantly increase in the upper and pelvis separation angles during load, foot contact, and pre-swing compared with U11 and U12 (ES = 0.131, 0.793, and 0.480). CONCLUSION: Various changes in batting kinematics occurred among each age group. Notably, U12 and U13 had the greater upper trunk-to-pelvis separation angle at foot contact and pre-swing compared to U11. Therefore, it would be important for the instruction of younger baseball players to understand the underdevelopment of trunk separation when batting and encourage the acquisition of such separation movements.

Extent of regional lymphadenectomy and number-based nodal classification for non-ampullary duodenal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). METHODS: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. RESULTS: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). CONCLUSIONS: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification.

Oral Administration of Glucosylceramide Suppresses Tumor Growth by Affecting the Ceramide/Sphingosine-1-Phosphate Balance in Breast Cancer Tissue.

Background: Ceramide and sphingosine-1-phosphate (S1P) play opposing roles in cell death and survival, and maintain a dynamic balance called the sphingolipid rheostat. Glucosylceramide is a substrate to generate ceramide but its effect on breast cancer by oral administration was never tested. The purpose of this study was to reveal the anticancer activity of glucosylceramide and its potential as a new therapeutic agent in breast cancer. Methods: E0771 cells were inoculated into the breast tissue of female C57BL/6NJcl mice. Glucosylceramide was administered orally to the mice for nine consecutive days. The concentrations of sphingolipid mediators including ceramide, glucosylceramide, and S1P in tumor tissues and serum were determined by mass spectrometry. Results: Oral administration of glucosylceramide significantly suppressed E0771 tumor growth compared with the control group (P = 0.006). There were no significant differences in the serum concentrations of sphingolipid mediators including ceramide and S1P between the mice treated with glucosylceramide and control-treated mice. The ceramide concentration was significantly lower in tumor tissues (P = 0.026), and the S1P concentration was significantly higher than that in paired non-tumor tissues (P = 0.009). The S1P concentration in tumor tissues was significantly lower in mice treated with glucosylceramide than in control-treated mice (P = 0.001). The ceramide-to-S1P concentration ratio in tumor tissues was significantly higher in mice treated with glucosylceramide than in control-treated mice (P = 0.034). Conclusions: Breast tumors could enhance their survival by increasing S1P conversion from ceramide. Oral administration of glucosylceramide suppressed tumor growth by affecting the ceramide/S1P balance. Oral administration of glucosylceramide is a promising basis for a new therapeutic approach.

Solitary choroidal metastasis of distal cholangiocarcinoma: A case report.

Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1® for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity.

Risk factors of throwing injuries related to pitching mechanics in young baseball players: a longitudinal cohort study.

BACKGROUND: Risk factors for throwing injuries related to pitching mechanics are unknown. Insufficient pelvic rotation during pitching may be a risk factor for shoulder and elbow injury. This cohort study aimed to identify biomechanics risk factors for throwing injuries in young baseball players. We hypothesized that excessive mechanical load and motion errors would be risk factors for throwing injuries. METHODS: Young baseball pitchers (aged 8-9 years) were recruited from regional baseball leagues between December 2016 and December 2019. Pitching measurements were performed before the start of each season and after the end of the last season in December 2019. The trunk tilt angular displacement, pelvic rotation angular displacement, and forearm rotation angle were calculated using a markerless motion capture system. We also measured elbow varus torque using an accelerometer. After the initial test session, each participant was followed up for 3 years to determine the occurrence of throwing injuries. Players with throwing shoulder and elbow injuries were categorized into the throwing injury group, and those without shoulder and elbow pain for 3 years were categorized into the noninjured group. RESULTS: In this study, 97 baseball pitchers completed a 3-year follow-up. Among those participants, 66 (68.0%) had throwing injuries. A significant difference was observed between the throwing injury and noninjured groups, whereby the injured players had less pelvic rotation angular displacement. CONCLUSION: Insufficient pelvic rotation during pitching is a newly discovered risk factor related to throwing injuries.

Clinical Significance of Phosphorylated Sphingosine Kinase 1 Expression in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive, lipid mediator, produced by sphingosine kinase 1 (SphK1). In this study, we evaluated the expression of phosphorylated SphK1 (pSphK1) in patients with pancreatic ductal adenocarcinoma (PDAC) and investigated its clinical significance. MATERIALS AND METHODS: A total of 111 patients who underwent curative-intent resection for PDAC were enrolled. We investigated pSphK1 (Ser-225) expression in surgically resected specimens of PDAC using immunohistochemistry. The patients were divided into two groups according to pSphK1 immunoreactive expression: a pSphK1-high group (n=63) and a pSphK1-low group (n=48). RESULTS: Logistic regression analyses revealed that lymphatic invasion (p=0.007) was a significantly independent factor associated with high pSphK1 immunoreactive expression. The pSphK1-high group showed significantly worse disease-specific survival (DSS) than the pSphK1-low group (5-year DSS rate, 19.6% vs. 58.7%; p=0.001). High pSphK1 immunoreactive expression (hazard ratio=2.547; 95% confidence interval= 1.434-4.527; p=0.001) was an independent prognostic factor for DSS. CONCLUSION: High pSphK1 expression is independently associated with lymphatic invasion and unfavorable prognosis in PDAC patients. Thus, the SphK1-S1P axis may be important in mechanisms of tumor progression, such as lymphatic invasion, in PDAC patients.

Clinical significance of metastatic tumor deposit foci in rectal cancer in the lateral pelvic lymph node area.

BACKGROUND: Although previous studies have demonstrated that tumor deposits (TDs) are associated with worse prognosis in colon cancer, their clinical significance in rectal cancer has not been fully elucidated, especially in the lateral pelvic lymph node (LPLN) area. This study aimed to clarify the clinical significance of TDs, focusing on the number of metastatic foci, including lymph node metastases (LNMs) and TDs, in the LPLN area. METHODS: This retrospective study involved 226 consecutive patients with cStage II/III low rectal cancer who underwent LPLN dissection. Metastatic foci, including LNM and TD, in the LPLN area were defined as lateral pelvic metastases (LP-M) and were evaluated according to LP-M status: presence (absence vs. presence), histopathological classification (LNM vs. TD), and number (one to three vs. four or more). We evaluated the relapse-free survival of each model and compared them using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Forty-nine of 226 patients (22%) had LP-M, and 15 patients (7%) had TDs. The median number of LP-M per patient was one (range, 1-9). The best risk stratification power was observed for number (AIC, 758; c-index, 0.668) compared with presence (AIC, 759; c-index, 0.665) and histopathological classification (AIC, 761; c-index, 0.664). The number of LP-M was an independent prognostic factor for both relapse-free and overall survival, and was significantly associated with cumulative local recurrence. CONCLUSION: The number of metastatic foci, including LNMs and TDs, in the LPLN area is useful for risk stratification of patients with low rectal cancer.

Impact of anatomic resection on long-term survival in patients with hepatocellular carcinoma with T1-T2 disease or microscopic vascular invasion.

BACKGROUND: This study aimed to clarify potential candidates for anatomic resection (AR) among patients with pathological T1-T2 (pT1-T2) hepatocellular carcinoma (HCC) and to determine whether AR is effective for HCC with microscopic vascular invasion (MVI). METHODS: We retrospectively analyzed 288 patients with pT1a (n = 50), pT1b (n = 134) or pT2 (n = 104) HCC who underwent curative-intent resection between 1990 and 2010. Surgical outcomes were compared between patients who underwent AR (n = 189) and those who underwent nonanatomic resection (NAR; n = 99) according to pT category and MVI status. RESULTS: Patients who underwent AR were more likely to have good hepatic functional reserve and an aggressive primary tumor than those who underwent NAR. When patients were stratified according to pT category, AR had a more favorable impact on survival than NAR only in patients with pT2 HCC in univariate (5-year survival, 51.5% vs. 34.6%; p = 0.010) and multivariate analysis (hazard ratio 0.505; p = 0.014). However, AR had no impact on survival in patients with pT1a or pT1b HCC. In patients with MVI (n = 57), AR achieved better survival than NAR (5-year survival, 52.0% vs. 16.7%; p = 0.019) and was an independent prognostic factor (hazard ratio 0.335; p = 0.020). In patients without MVI (n = 231), there was no significant difference in survival between the two groups (p = 0.221). CONCLUSION: AR was identified as an independent factor in improved survival in patients with pT2 HCC or HCC with MVI.

Rational Extent of Regional Lymphadenectomy and the Prognostic Impact of the Number of Positive Lymph Nodes for Perihilar Cholangiocarcinoma.

BACKGROUND: The definition and classification of regional nodes are not standardized for perihilar cholangiocarcinoma. This study aimed to clarify the rational extent of regional lymphadenectomy and to elucidate the impact of number-based regional nodal classification on survival of patients with this disease. METHODS: Data of 136 patients with perihilar cholangiocarcinoma who underwent surgery were reviewed. The incidence of metastasis and the survival of patients with metastasis were calculated for each node group. RESULTS: The incidence of metastasis for the node groups in the hepatoduodenal ligament (denoted as no. 12) ranged from 3.7% to 25.4%, with 5-year disease-specific survival of 12.9% to 33.3% for patients with metastasis. The incidences of metastasis in the common hepatic artery (no. 8) and posterior superior pancreaticoduodenal (no. 13a) node groups were 14.4% and 11.2%, respectively, with 5-year disease-specific survival rates of 16.7% and 20.0% for the patients with metastasis. When these node groups were defined as regional nodes, the 5-year disease-specific survival rates for the patients with pN0 (n = 80), pN1 (1-3 positive nodes, n = 38), and pN2 (≥ 4 positive nodes, n = 18) were 61.4%, 22.9%, and 17.6%, respectively (p < 0.001). The pN classification was independently associated with disease-specific survival (p < 0.001). When only the no. 12 node groups were regarded as regional nodes, pN classification failed to stratify the patients prognostically. CONCLUSIONS: No. 8 and no. 13a node groups should be considered regional nodes in addition to no. 12 node groups and should be dissected. The number-based regional nodal classification allows patients with this disease to be stratified prognostically.

[Radical Resection Followed by Chemotherapy for Intrahepatic Cholangiocarcinoma with Lymph Node Metastases-Report of a Long-Term Survivor].

We report a case of intrahepatic cholangiocarcinoma(ICC)with lymph node metastases in which long-term survival was achieved after surgery followed by chemotherapy. A 69-year-old man underwent left hepatectomy, extrahepatic bile duct resection, and lymph node dissection for ICC located mainly in segment 4 of the liver with enlarged lymph nodes in the hepatoduodenal ligament. The histopathologically confirmed diagnosis was ICC(T2N1M0, Stage ⅣA)with 3 positive lymph nodes(No. 12a1, No. 12p1, and No. 12p2). He received chemotherapy with gemcitabine(GEM)plus cisplatin(CDDP)for 9 months, followed by GEM monotherapy for 4 months, and then S-1 monotherapy was started. A right lung nodule was detected 12 months after the initiation of S-1 monotherapy. He received GEM plus S-1 therapy for 28 months, followed by S-1 monotherapy, leading to disappearance of the lung nodule. He remains alive and well without disease 78 months after surgery. Our experience in this case suggests that radical resection followed by chemotherapy may provide a survival benefit in selected patients who have ICC with nodal disease.