Incidence and treatment of metachronous gastric cancer after proximal gastrectomy.

BACKGROUND AND PURPOSE: Proximal gastrectomy (PG) is a widely accepted function-preserving surgical procedure; however, the incidence and treatment of metachronous gastric cancer (MGC) after PG have been the subject of a number of reports. METHODS: We collected data from 1576 consecutive patients who underwent gastrectomy for gastric cancer between January, 2003 and December, 2010, and analyzed the outcomes of 671 patients treated with PG or distal gastrectomy (DG) for cT1N0 disease. We also discuss the treatments for MGC. RESULTS: MGC was diagnosed within a median follow-up of 52.8 months after PG and DG in six (6.6%) and nine (1.8%) patients, respectively. The cumulative prevalence of MGC after PG was significantly higher than that after DG; P = 0.005. Univariate and multivariate analysis revealed male sex and PG as significant risk factors for MGC (P = 0.014 and P = 0.026, respectively). Five of the six patients who underwent PG were treated by endoscopic submucosal dissection. CONCLUSIONS: The incidence of MGC after PG was significantly higher than that after DG. However, most of the MGCs that developed after PG could be treated by endoscopic submucosal dissection.

Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors.

BACKGROUND AND STUDY AIM: Malignancy in pancreatic neuroendocrine tumors (PNETs) is graded by assessing the resected specimens according to the World Health Organization (WHO) 2010 criteria. The feasibility of such grading using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens remains unclear. The aim of this study was to ascertain the optimal method of measuring the Ki-67 index in EUS-FNA specimens, using resected specimens as the criterion standard. PATIENTS AND METHODS: A total of 58 consecutive patients diagnosed with PNETs between March 1998 and May 2011 were included. The study measured intratumoral Ki-67 index heterogeneity, concordance rates of PNET grading by EUS-FNA with grade of the resected tumor, optimal method of measuring the Ki-67 index in EUS-FNA specimens, and survival analysis based on EUS-FNA specimen grading. RESULTS: Intratumoral dispersion of Ki-67 index in resected specimens was 0.033 for Grade 1 and 0.782 for Grade 2 tumors (P<0.001). Concordance rates for WHO classification between EUS-FNA and resected specimens were 74.0% using the mean Ki-67 index in EUS-FNA specimens and 77.8% using the highest Ki-67 index. The concordance rate rose to 90% when EUS-FNA samples with less than 2000 tumor cells were excluded (26% of EUS-FNA cases). The Kaplan-Meier survival curves were significantly stratified by the EUS-FNA grading of PNETs with 5-year survival rates of 100%, 58.3%, and 0%, for Grade 1, Grade 2, and neuroendocrine carcinoma (NEC) tumors, respectively. CONCLUSIONS: Grading of PNETs by the highest Ki-67 index in EUS-FNA specimens with adequate cellularity has a high concordance with grading of resected specimens, and can predict long term patient survival with high accuracy.

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population.

BACKGROUND: The ToGA trial demonstrated the beneficial effect of trastuzumab in gastric cancer patients with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors. Therefore, evaluation of the relationship between HER2 expression and gastric cancer biology using a validated system has become an even more important task. Herein, we verified the correlation between HER2 overexpression in the tumor and the clinical course of gastric cancer patients. METHODS: A total of 1,006 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using the tissue microarrays approach. HER2 expression was determined based on an immunohistochemistry score of 3+, or an immunohistochemistry score of 2+ plus HER2 gene amplification as detected by double-color fluorescent in situ hybridization. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Then, in 948 patients who had undergone curative resection, HER2 status was compared with the survival. RESULTS: HER2 overexpression was detected in 118 (11.7 %) patients. HER2 overexpression was correlated with age, gender, grade of differentiation, expanding growth pattern, and nodal status. In the survival analysis, HER2 overexpression was not found to be correlated with either disease-specific survival or recurrence-free survival. CONCLUSIONS: HER2 overexpression in the tumor was not identified as a significant prognostic factor in patients with operable gastric cancer. The HER2-targeted therapy may be beneficial in a proportion of cases.

Limited subtotal gastrectomy for early remnant gastric cancer.

BACKGROUND: Detection of early remnant gastric cancer (ERGC) is increasing as a result of the development of endoscopic technology and a surveillance program. The aim of this study was to evaluate the results of limited subtotal gastrectomy (SG) surgery for ERGC compared to total gastrectomy (TG). METHODS: We retrospectively reviewed a database of 72 consecutive patients with remnant gastric cancer who underwent laparotomy at the National Cancer Center Hospital East between January 1993 and December 2008. Thirty-five patients with a preoperative diagnosis of ERGC underwent curative resection: 13 SG and 22 conventional TG. Patients and tumor characteristics, operative results, and postoperative assessments 1 year after surgery were compared between the two groups. RESULTS: Operating time, blood transfusion, and hospital stay were similar in the two groups. In the SG group, blood loss and postoperative recovery of body weight tended to be better than in the TG group. There was no dumping syndrome in the SG group, while this occurred in three patients in the TG group. The levels of hemoglobin and total protein were higher 1 year after remnant gastrectomy in the SG group than in the TG group. No recurrence of gastric cancer was detected in the SG group during median follow-up of 99.2 months. CONCLUSION: In comparison to TG, limited SG surgery for ERGC improved the postoperative course, with no recurrence of cancer. Therefore, SG is a safe and effective treatment for ERGC.

NC-6300, an epirubicin-incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin.

Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin-incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC-6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid-labile hydrazone bond. The conjugate forms a micellar structure of 40-80 nm in diameter in an aqueous milieu. NC-6300 (10, 15 mg/kg) and epirubicin (10 mg/kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL/6 mice that were given NC-6300 (10 mg/kg) or epirubicin (10 mg/kg) in nine doses over 12 weeks. NC-6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC-6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin-treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC-6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC-6300 in patients with hepatocellular carcinoma or other cancers.

Impaired mental health among the bereaved spouses of cancer patients.

OBJECTIVE: Few cancer physicians routinely provide bereavement follow-up in clinical practice. The purpose of this study was to identify the prevalence of impaired mental health among the bereaved spouses over several years and explore the indicators for early detection of high-risk spouses during end-of life (EOL) care. METHODS: A cross-sectional mail survey was conducted for the bereaved spouses of patients who had died at the National Cancer Center Hospital of Japan. Bereaved spouses with potential psychiatric disorders were identified by the cut-off score of the 28-item General Health Questionnaire. Associated factors of potential psychiatric disorders were explored by logistic regression analysis. RESULTS: A total of 821 spouses experiencing bereavement from 7 months to 7 years returned the questionnaires. Overall mean prevalence of potential psychiatric disorders was 44% (360/821). Bereaved spouses 'under 55 years' (71%) or '2 years after bereavement' (59%) revealed a significantly higher prevalence (p < 0.01). Associated factors during EOL care were several characteristics such as 'spouses' history of psychiatric disorder (odds ratio (OR) = 3.19), 'patients' with stomach cancer (OR = 1.87), and 'patients' using psychiatric consultation services (OR = 1.52) as well as spouses' dissatisfaction with EOL care such as 'physicians' treatment of physical symptoms' (OR = 3.44) and 'time spent communicating with patients' (OR = 1.55). CONCLUSIONS: Nearly half the bereaved spouses showed potential psychiatric disorders even 7 years after bereavement. Patients' psychological distress, spouses' history of psychiatric disorder, and dissatisfaction with EOL care were indicators of high-risk spouses.

Laparoscopic proximal gastrectomy with jejunal interposition for gastric cancer in the proximal third of the stomach: a retrospective comparison with open surgery.

BACKGROUND: The incidence of cancer in the proximal third of the stomach is increasing. Laparoscopic proximal gastrectomy (LPG) seems an attractive option for the treatment of early-stage proximal gastric cancer but has not gained wide acceptance because of technical difficulties, including the prevention of severe reflux. In this study, we describe our technique for LPG with jejunal interposition (LPG-IP) and evaluate its safety and feasibility. METHODS: In this retrospective analysis, we reviewed the data of patients with proximal gastric cancer who underwent LPG-IP (n = 22) or the same procedure with open surgery (OPG-IP; n = 68) between January 2008 and September 2011. Short-term surgical variables and outcomes were compared between the groups. The reconstruction method was the same in both groups, with creation of a 15 cm, single-loop, jejunal interposition for anastomosis. RESULTS: There were no differences in patient or tumor characteristics between the groups. Operation time was longer in the LGP-IP group (233 vs. 201 min, p = 0.0002) and estimated blood loss was significantly less (20 vs. 242 g, p < 0.0001). The average number of harvested lymph nodes did not differ between the two groups (17 vs. 20). There also were no differences in the incidence of leakage at the esophagojejunostomy anastomosis (9.1 vs. 7.4%) or other postoperative complications (27 vs. 32%). The number of times additional postoperative analgesia was required was significantly less in the LPG-IP group compared with the OPG-IP group (2 vs. 4, p < 0.0001). CONCLUSIONS: LPG-IP has equivalent safety and curability compared with OPG-IP. Our results imply that LPG-IP may lead to faster recovery, better cosmesis, and improved quality of life in the short-term compared with OPG-IP. Because of the limitations of retrospective analysis, a further study should be conducted to obtain definitive conclusions.

Isolated caudate lobectomy with pancreatoduodenectomy for a bile duct cancer.

BACKGROUND: In patients with distal bile duct cancer involving the hepatic hilus, a major hepatectomy concomitant with pancreatoduodenectomy (HPD) is sometimes ideal to obtain a cancer-free resection margin. However, the surgical invasiveness of HPD is considerable. PATIENTS AND METHODS: We present our treatment option for patients with distal bile duct cancer showing mucosal spreading to the hepatic hilum associated with impaired liver function. To minimize resection volume of the liver, an isolated caudate lobectomy (CL) with pancreatoduodenectomy (PD) using an anterior liver splitting approach is presented. Liver transection lines and bile duct resection points correspond complete with our standard right and left hemihepatectomies with CL for perihilar cholangiocarcinoma. RESULTS: Total operation time was 765 min, and pedicle occlusion time was 124 min, respectively. Although the proximal mucosal cancer extension was identified at both the right and the left hepatic ducts, all resection margins were negative for cancer. CONCLUSIONS: Isolated CL with PD is an alternative radical treatment option for bile duct cancer patients with impaired liver function.

Infection control for prevention of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND/AIMS: Effectiveness of infection control for prevention of pancreatic fistula (PF) after pancreaticoduodenectomy (PD) is not clear. We analyzed the impact of infection on the development of PF and examined the effect of enhanced infection control to prevent PF. METHODOLOGY: Amylase level (D-amylase) and bacterial culture (D-culture) of drainage fluid were evaluated on POD 1, 3, 5 and 7, in 90 consecutive patients with soft pancreas who underwent PD. The study period was divided into two periods. The relationship between D-amylase and D-culture was examined, and the clinicopathological factors predicting PF were analyzed in the first period. Then, anti-infection measures were introduced in the second period, and the effect of enhanced infection control was examined. RESULTS: Twenty-nine out of 58 patients (50.0%) developed PF in the first period. D-amylase were higher in patients with D-culture infection than in those without it (p<0.05). D-amylase above 10,000IU/L on POD1 and D-culture infection on POD3 were independent predictive factors for PF by multivariate analysis (p<0.01). After introduction of enhanced infection control in the second period, four out of 32 patients (12.5%) developed PF. The rates of PF and D-culture infection were significantly reduced (p<0.05). CONCLUSIONS: Infection of drainage fluid is related to an increased level of amylase, resulting in PF. Enhanced infection control can effectively prevent PF after PD in soft pancreas.

Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head.

Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor-associated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC.

Clinicopathological features and prognostic factors of adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single institution in Japan.

BACKGROUND: Treatment strategy for adenocarcinoma of the esophagogastric junction (AEG) remains controversial. The aims of this study are to evaluate results of surgery for AEG, to clarify clinicopathological differences according to the Siewert classification, and to define prognostic factors. METHODS: We retrospectively analyzed 179 consecutive patients with Siewert type I, II, and III AEG who underwent curative (R0) resection at the National Cancer Center Hospital East between January 1993 and December 2008. RESULTS: Patients with AEG were divided according to tumor: 10 type I (5.6%), 107 type II (59.8%), and 62 type III (34.6%). Larger, deeper tumors and nodal metastasis were more common in type III than type II tumors. No significant differences were seen in 5-year survival rates among the three types: type I (51.4%), type II (51.8%), and type III (62.6%). Multivariate analysis showed that depth of tumor and mediastinal lymph node metastasis were independent prognostic indicators. The recurrence rate for patients with mediastinal lymph node metastasis was 87.5%. The risk factors for mediastinal lymph node metastasis were length of esophageal invasion and histopathological grade. CONCLUSIONS: Mediastinal lymph node metastasis and tumor depth were significant and independent factors for poor prognosis after R0 resection for AEG. Esophageal invasion and histopathological grade were significant and independent factors for mediastinal lymph node metastasis.

Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy.

OBJECTIVES: A global consensus on how to treat recurrent pancreatic cancer after adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist. METHODS: We retrospectively reviewed the clinical data of 41 patients with recurrences who were subsequently treated with chemotherapy. RESULTS: The patients were divided into two groups according to the time until recurrence after the completion of ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an ADJ-Rec ≥ 6 months (n = 16). The disease control rate, the progression-free survival after treatment for recurrence and the overall survival after recurrence for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186), and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the patients with an ADJ-Rec < 6 months into two groups: patients treated with gemcitabine (n = 6) and those treated with alternative regimens including fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients treated with the alternative regimens had a better outcome than those treated with gemcitabine. CONCLUSIONS: Fluoropyrimidine-containing regimens may be a reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6 months.

Clinicopathological features of stomach cancer with invasive micropapillary component.

BACKGROUND: Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer. METHODS: We retrospectively analyzed 930 patients diagnosed with gastric cancer who underwent gastrectomy, and we then histopathologically evaluated the existence of a regional invasive micropapillary component. Clinicopathological features were investigated in patients with an invasive micropapillary component and compared with such features in 100 patients with gastric adenocarcinoma, selected as stage-matched controls, who underwent gastrectomy during the same period. RESULTS: Of the 930 patients, 14 were histopathologically diagnosed with gastric cancer with a regional invasive micropapillary component. There were no significant differences in age, gender, tumor location, macroscopic type, or type of surgery between patients with an invasive micropapillary component and the pT-matched controls. Histopathologically, significant differences were observed in lymphatic infiltration, venous invasion, the percentage of cases with lymph node metastasis, and the median number of metastatic lymph nodes. The three-year disease-free and overall survival rates of patients with an invasive micropapillary component were 40.5 and 59.3%, respectively, compared with those for the stage-matched controls, which were 72.6 and 80.6%, respectively (p = 0.02 and 0.07). CONCLUSIONS: Patients with gastric cancer with a regional invasive micropapillary component showed marked cancer infiltration in the lymphatic pathway and poor prognosis after gastrectomy.

Psychological states and coping strategies after bereavement among spouses of cancer patients: a quantitative study in Japan.

PURPOSE: The purposes of this study were (1) to characterize psychological states and coping strategies after bereavement among spouses of cancer patients in Japan and (2) to explore the factors associated with psychological states in oncology settings. METHODS: In March 2009, questionnaires to assess spouses' psychological states, coping strategies, and mental health states (GHQ-28) were sent after patients died at the National Cancer Center of Japan. To address the first purpose, exploratory factor analysis, gender comparison, and calculation of correlation with age, time since bereavement, and mental health states were conducted. Hierarchical regression analysis was conducted to address the second purpose. RESULTS: A total of 821 spouses experiencing bereavement for 7 months to 7 years participated in the study. Psychological states revealed three factor structures: "Anxiety/Depression/Anger", "Yearning", and "Acceptance/Future-Oriented Feelings". Coping strategies also revealed three factor structures: "Distraction", "Continuing Bonds", and "Social Sharing/Reconstruction". Coping strategies represented 18 % to 34 % of each factor associated with psychological states, whereas the characteristics of bereaved spouses and deceased patients represented 6 % and less than 6 %, respectively. More "Distraction and Social Sharing/Reconstruction" and less "Continuing Bonds" were significantly associated coping strategies for achieving "Acceptance/Future-Oriented Feelings" (p < 0.01). CONCLUSIONS: Both psychological states and coping strategies after bereavement revealed three factor structures. Coping strategies was the primary, bereaved spouses' characteristics was the secondary, and deceased patients' characteristics was the tertiary factor associated with psychological states. Enhancing "Distraction" and "Social Sharing/Reconstruction", and reducing "Continuing Bonds" might be promising strategies for achieving positive psychological states of the bereaved.

Surgical outcome of liver transection by the crush-clamping technique combined with Harmonic FOCUS™.

BACKGROUND: New energy devices are constantly being introduced for all types of surgery, including liver surgery. These devices help surgeons perform operations. Meanwhile, intraoperative blood loss is a concern of liver surgeons. Various methods to reduce intraoperative bleeding during liver resection have been reported. There are some reports that the use of energy devices was effective for liver transection. Recently, the Harmonic FOCUS™ (HF), an ultrasonically activated device, was developed. The shape of the HF is similar to that of Kelly forceps. Hepatectomy can be performed by the clamp-crushing method using the HF instead of Kelly forceps. We obtained good results of liver resection with the HF, and report these outcomes in this study. METHODS: From November 2009 to March 2011, a total of 51 patients underwent hepatectomy with the use of the HF. The control group consisted of 59 patients who underwent hepatectomy without the HF from February 2009 to September 2009. The surgical outcomes were evaluated and compared retrospectively. RESULTS: Mean blood loss was 640 mL in the HF group compared to 1,176 mL in the control group. The number of patients needing a blood transfusion was smaller in the HF group (p = 0.02). Mean operative time was shorter in the HF group (171 vs. 235 min, p < 0.001). All these surgical outcomes were significantly better in the HF group. Postoperative morbidity was not increased in the HF group, and we could perform liver transection safely. CONCLUSION: The crush-clamping method combined with the HF is effective for liver transection. Liver resection can be performed quickly using this method.

Intraductal oncocytic papillary neoplasm of the extrahepatic bile duct: report of a case.

We report a rare case of an intraductal oncocytic papillary neoplasm (IOPN) of the extrahepatic bile duct. A 66-year-old man was admitted to our hospital for investigation of right-sided back pain. Ultrasonography, computed tomography and magnetic resonance imaging showed a papillary lesion, 3 cm in diameter, in the middle bile duct, invaginating into the cystic duct. We made a provisional diagnosis of middle bile duct cancer and performed substomach-preserving pancreatoduodenectomy. Macroscopically, the middle bile duct contained a two-humped papillary tumor, one tip of which invaginated into the cystic duct. Microscopically, the tumor consisted of cuboidal cells with abundant eosinophilic cytoplasm resembling that of oncocytes and a fine fibrovascular core. The tumor cells were stained strongly with antimitochondria antibody. Based on these findings, the tumor was diagnosed histologically as IOPN of the extrahepatic bile duct. The patient died of prostate cancer 51 months after surgery, but without evidence of recurrence of the IOPN.

D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer.

BACKGROUND: Gastrectomy with D2 lymphadenectomy is the standard treatment for curable gastric cancer in eastern Asia. Whether the addition of para-aortic nodal dissection (PAND) to D2 lymphadenectomy for stage T2, T3, or T4 tumors improves survival is controversial. We conducted a randomized, controlled trial at 24 hospitals in Japan to compare D2 lymphadenectomy alone with D2 lymphadenectomy plus PAND in patients undergoing gastrectomy for curable gastric cancer. METHODS: Between July 1995 and April 2001, 523 patients with curable stage T2b, T3, or T4 gastric cancer were randomly assigned during surgery to D2 lymphadenectomy alone (263 patients) or to D2 lymphadenectomy plus PAND (260 patients). We did not permit any adjuvant therapy before the recurrence of cancer. The primary end point was overall survival. RESULTS: The rates of surgery-related complications among patients assigned to D2 lymphadenectomy alone and those assigned to D2 lymphadenectomy plus PAND were 20.9% and 28.1%, respectively (P=0.07). There were no significant differences between the two groups in the frequencies of anastomotic leakage, pancreatic fistula, abdominal abscess, pneumonia, or death from any cause within 30 days after surgery (the rate of death was 0.8% in each group). The median operation time was 63 minutes longer and the median blood loss was 230 ml greater in the group assigned to D2 lymphadenectomy plus PAND. The 5-year overall survival rate was 69.2% for the group assigned to D2 lymphadenectomy alone and 70.3% for the group assigned to D2 lymphadenectomy plus PAND; the hazard ratio for death was 1.03 (95% confidence interval [CI], 0.77 to 1.37; P=0.85). There were no significant differences in recurrence-free survival between the two groups; the hazard ratio for recurrence was 1.08 (95% CI, 0.83 to 1.42; P=0.56). CONCLUSIONS: As compared with D2 lymphadenectomy alone, treatment with D2 lymphadenectomy plus PAND does not improve the survival rate in curable gastric cancer. (ClinicalTrials.gov number, NCT00149279.)

Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer, a multicenter phase III clinical trial was conducted in Japan. PATIENTS AND METHODS: From January 1993 to March 1998, 268 patients were randomized to adjuvant chemotherapy (135 patients) or surgery alone (133 patients). All patients underwent gastrectomy with D2 or greater lymph node dissection. The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure, postoperative intravenous cisplatin (day 14) and 5-fluorouracil (day 14-16), and daily oral FU (UFT) starting 4 weeks after surgery for 12 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. RESULTS: Fifty-two patients (38.5%) in the adjuvant chemotherapy arm completed the chemotherapy regimen. There were 4 (1.49%) treatment-related deaths, 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm (2 did not receive chemotherapy). Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm. There was no significant difference in 5-year overall survival (62.0% adjuvant chemotherapy vs. 60.9% surgery-alone, P = 0.482) and 5-year relapse-free survival rates (57.5% adjuvant chemotherapy vs. 55.6% surgery-alone; P = 0.512). CONCLUSION: There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection.

Surgical outcomes of multicentric adenocarcinomas of the biliary tract.

OBJECTIVE: In comparison to single biliary cancers, distinct features of biliary multicentric adenocarcinomas are not yet clear. METHODS: From July 1992 to July 2009, 393 patients underwent surgery for cancers of the biliary tract at the National Cancer Center Hospital East, Kashiwa, Japan. Clinicopathological characteristics and surgical outcomes of multicentric biliary adenocarcinoma were compared with those of single cancers. RESULTS: During the period, 10 cases (2.5%) with multicentric cancer (6 synchronous and 4 metachronous cancers) were found among 393 cases of biliary cancer. Pathologically, compared with single cancers, multicentric adenocarcinomas were more likely to be early cancers and to be papillary carcinomas with both superficial epithelial tumor spread and extensive dysplastic epithelium, but were less likely to have lymph node metastases (P < 0.01). The proportion of multicentric cancers among early papillary cancers was high (9/24, 37.5%). Clinically, no recurrences were detected in lymph nodes, peritoneum or distant organs, but one recurrence in the remnant bile duct. Only one patient died from cancer progression. The overall survival of patients with multicentric adenocarcinomas was statistically the same as that of single cancers (median survival: 69 vs. 30 months, P = 0.47). CONCLUSIONS: Multicentric adenocarcinomas of the biliary tract have distinct features compared with single cancers.

Predictive value of baseline neutrophil/lymphocyte ratio for T4 disease in wall-penetrating gastric cancer.

BACKGROUND: Multimodality therapy has been used in the management of gastric cancer associated with locoregional spread. However, the accurate clinical staging still remains to be established. The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is reported to be an easily assessable prognostic factor in cancer patients. We evaluated the predictive significance of the NLR and other serological parameters in patients with wall-penetrating gastric cancer. METHODS: Two hundred sixty-two patients who underwent gastric cancer surgery between 2002 and 2005 were identified retrospectively. Wall penetration was defined as wall invasion deeper than the muscularis propria (≥ T2). Blood data were collected from routinely performed blood examinations before treatment and were analyzed with respect to T stage, nodal status, and histological features. A high NLR was defined as less than 3.2 based on ROC curve analysis, and the predictive value of a high NLR for T4 cancer was evaluated. RESULTS: Elevated levels of NLR (P = 0.004) and C-reactive protein (CRP) (P = 0.017) and the decrease in lymphocyte count (Lym, P = 0.032) and serum hemoglobin (Hb, P < 0.001) were correlated with the T stage, but there was no meaningful correlation with either positive nodal status or histological differentiation. With respect to the predictive value for stage T4, an elevated NLR (OR = 2.206, 95% CI = 1.187-4.100; P = 0.012), decrease of Hb (OR = 1.875, 95% CI = 1.005-3.500; P = 0.048), and poorly differentiated histology (OR = 3.134, 95% CI = 1.593-6.167; P = 0.001) were identified as independent predictive factors. CONCLUSION: Our findings suggest that the preoperative values of the NLR may be reliable for predicting T4 disease.