Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). BACKGROUND: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. METHODS: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. RESULTS: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. CONCLUSIONS: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER).

BACKGROUND: Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival. RESULTS: Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events. CONCLUSION: S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.

Phase II study of first-line chemotherapy with uracil-tegafur plus oral leucovorin in elderly (≥75 years) Japanese patients with metastatic colorectal cancer: SGOSG-CR0501 study.

BACKGROUND: Oral uracil-tegafur and leucovorin (UFT/LV) therapy for elderly patients with metastatic colorectal cancer (mCRC) requires careful handling in Western countries because of a high incidence (≥20 %) of grade 3 diarrhea. However, its efficacy and safety for elderly Asian patients have not been investigated. METHODS: In this multicenter cooperative phase II study, the eligibility criteria were: age of 75 years or older, no prior chemotherapy, and histologically confirmed colorectal cancer with one or more measurable lesions. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally for 28 days followed by a 7-day rest period. RESULTS: Twenty-one patients were enrolled in this study (prior to study termination after approval of bevacizumab), and all patients were eligible for efficacy and safety analysis. The median age was 79 years (range, 75-83 years). The majority of patients (95 %) had ECOG Performance Status 0 or 1. The overall response rate was 33 % (95 % confidence interval [CI], 18-53 %). The median progression-free and overall survivals were 5.3 months (95 % CI 4.0-7.9 months) and 18 months (95 % CI 13-21 months), respectively. Grade 3 or greater adverse events included anorexia (10 %), diarrhea (10 %), and leukopenia (5 %). These results were compatible with those seen in Japanese patients in a previous bridging study between Japan and the US, in which patients under 75 years old were evaluated. CONCLUSIONS: UFT/LV therapy was safe and feasible in elderly Japanese patients with mCRC, and further study of UFT/LV therapy in combination with bevacizumab is warranted.

Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma.

BACKGROUND: Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes. METHODS: Medical records were reviewed for 86 patients who underwent curative resection for ampullary adenocarcinoma between 2000 and 2012 at 12 principal hospitals in Kagawa, Japan. RESULTS: Resection was most common among 75-79-year-old patients. Actuarial 1-, 3-, and 5-year postoperative survival rates for ampullary adenocarcinoma were 90%, 72.3%, and 69.1%, respectively. Preoperative biliary drainage; serum CA19-9 and total bilirubin levels; pathological grade; perineural, vascular, pancreatic, and duodenal invasion; nodal metastasis; UICC-T stage; and pancreatobiliary subtype were predictors of poor survival. An elevated serum CA19-9 level; an elevated total bilirubin level; lymphatic, vascular, perineural, and pancreatic invasion; and advanced overall tumor stage were more common in patients with pancreatobiliary-type tumors than in patients with intestinal-type tumors. Additionally, pathologic subtype analysis showed that each subtype had distinct prognostic factors. CONCLUSIONS: Preoperative elevated serum CA19-9 and total bilirubin levels are prognostic factors for ampullary adenocarcinoma, and are both associated with pancreatobiliary-type tumors. Surgeons should be aware of these factors because pancreatobiliary-type adenocarcinoma is aggressively invasive and is associated with poor survival.

Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of the status of the 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4). BACKGROUND: Recent whole-exome sequencing had shown that the landscape of the pancreatic ductal adenocarcinoma (PDAC) genome is notable for 4 frequently mutated genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4). METHODS: We determined immunohistochemically the status of TP53, CDKN2A/p16, and SMAD4/DPC4 among the 4 genes because the KRAS gene is mutated in virtually all PDAC patients, and analyzed relationships with clinicopathological findings, including survival and patterns of disease progression, in 106 patients with PDAC undergoing radical surgery. RESULTS: Abnormal immunolabeling of p53 was detected in 81.1% of PDACs and was significantly associated with tumor dedifferentiation (P = 0.022) and the presence of locoregional recurrence (P = 0.020). Loss of p16 and Smad4/Dpc4 immunolabeling was identified in 67.0% and 60.4%, respectively. Loss of p16 immunolabeling was associated with lymphatic invasion (P = 0.012) and postoperative widespread metastases (P < 0.001). A significant correlation was found between Smad4/Dpc4 immunolabeling and tumor size (P = 0.006), lymphatic invasion (P = 0.033), and lymph node metastasis (P = 0.006). Interestingly, all of the 6 patients demonstrating 5-year survival had intact SMAD4/DPC4. Kaplan-Meier survival analysis showed that lymph node metastasis (P = 0.001), lymphatic invasion (P = 0.008), the tumor (T) factor (T3 vs. T1/T2, P = 0.004), loss of p16 immunolabeling (P = 0.029), and loss of Smad4/Dpc4 immunolabeling (P < 0.001) were significantly associated with shorter overall survival. Multivariate analysis revealed that loss of Smad4/Dpc4 immunolabeling was an independent and significant poor prognostic factor for overall and disease-free survival. On analysis of combinations of the status of these 3 genes, increasing number of alterations reflected poorer survival. CONCLUSIONS: Genetic alterations of these 3 genes and their accumulation are strongly associated with malignant behavior of PDAC. Their immunohistochemical assessment at the time of diagnosis may provide a new prognostic tool, assisting in deciding optimal therapeutic strategies for patients.

[A case of effective chemoradiotherapy using docetaxel and nedaplatin for recurrent anal canal squamous cell carcinoma].

69-year-old woman underwent resection of a tumor diagnosed as squamous cell carcinoma of the anal canal. After 4 years and 5 months, computed tomography(CT)showed abdominal and pelvic lymph node swelling. Chemotherapy consisting of biweekly docetaxel(35mg/m2)+nedaplatin(35mg/m2)achieved a partial response. After 20 cycles of chemotherapy, the patient was treated with radiotherapy because of a pelvic lymph node recurrence. Since then, no recurrence has occurred for 16 months. The adverse event was Grade 2 in leucopenia and neutropenia. This case suggested that chemoradiotherapy consisting of docetaxel +nedaplatin may be effective and safe for treating anal canal squamous cell carcinoma.

Verification of the Nutritional and Dietary Factors Associated with Skeletal Muscle Index in Japanese Patients with Nonalcoholic Fatty Liver Disease.

We sought to identify the frequencies of presarcopenia, sarcopenia, and sarcopenic obesity in patients with nonalcoholic fatty liver disease (NAFLD) and to cross-sectionally determine the nutritional and dietary factors associated with loss of skeletal muscle mass in such patients. Dietary and body component changes produced by a diet intervention were longitudinally investigated. Forty-six NAFLD patients (24 males and 22 females) were enrolled. A second diet treatment was performed at 6 months after entry in 19 of the enrolled patients (6 males and 13 females). Body compositions and dietary nutrients at six months later were compared with those at entry. Three of the 24 (13%) males and four of the 22 (18%) females fulfilled the criteria for presarcopenia and one (5%) female NAFLD patient was in the criteria for sarcopenia at baseline. None of the patients were in the criteria for sarcopenic obesity. The factors associated with skeletal muscle index in the males were body mass index (BMI), insulin-like growth factor-1, total energy intake, and lipid intake, but only BMI and bone mineral density in females at baseline. The diet intervention decreased the skeletal muscle mass in the 6 males by decreasing the total energy intake via lower protein and lipid intakes and improved their liver dysfunction. In the 13 females, a decrease in total energy intake via lower carbohydrate and lipid intake did not change the skeletal muscle mass. These results suggest that loss of skeletal muscle mass is frequently observed in nonobese NAFLD patients and that the frequency of sarcopenic obesity seems to be rare in NAFLD patients. The nutritional and dietary factors that regulate loss of skeletal muscle mass were distinct between our male and female NAFLD patients. Thus, the skeletal muscle mass of such patients as well as their body weight and liver function should be monitored during diet interventions.

Immunohistochemically detected expression of p27(Kip1) and Skp2 predicts survival in patients with intrahepatic cholangiocarcinomas.

In intrahepatic cholangiocarcinomas (ICCs), the prognostic significance of p27(Kip1), a cyclin-dependent kinase inhibitor, remains controversial, and there have been no studies of degradation pathway associated proteins, S-phase kinase-interacting protein (Skp2), and Jun activation domain-binding protein-1 (Jab1). In the present study of 74 patients with ICC-mass forming type (ICC-MF) undergoing radical surgery, we determined immunohistochemical expression of p27(Kip1), Skp2, and Jab1 and examined relationships with clinicopathologic findings and patient survival. On the basis of the average of labeling indices, we set cutoff values to define high and low expressors and divided the cases into two groups. A statistically significant correlation was found between low p27(Kip1) expression and lymph node metastasis (P = .009). Patient survival in the low p27(Kip1) expression group (n = 25) was also significantly worse than that in the high p27(Kip1) expression group (n = 49, P = .0007). A significant inverse correlation was found between p27(Kip1) and Skp2 expression (P = .016). High Skp2 expression (n = 36) was significantly associated with poor prognosis (P = .0046). High Jab1 expression was observed in 32 cases, but there was no statistically significant relationship with clinicopathologic findings or patient survival. The multivariate analysis revealed that low p27(Kip1) and high Skp2 expression are independent and significant factors of poor prognosis. The results suggest that low p27(Kip1) and high Skp2 expression are associated with aggressive tumor behavior, and these cell-cycle regulators are useful markers to predict outcome of patients with ICC-MF.

A patient with unresectable advanced pancreatic cancer achieving long-term survival with gemcitabine chemotherapy.

A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased, and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites, liver metastasis, or peritoneal dissemination was observed. The entire pancreas was a hard mass, and a needle biopsy was obtained from the head, body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed, and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However, the patient suffered relatively severe side effects, and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore, weekly chemotherapy was stopped and was changed to monthly administration. To date, for 4 years after chemotherapy, the tumor has not reappeared.

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).

BACKGROUND: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. PATIENTS AND METHODS: The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. CONCLUSION: UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.

Application of preoperative portal vein embolization before major hepatic resection in patients with normal or abnormal liver parenchyma.

BACKGROUND: Clinical parameters influencing the effect of preoperative portal vein embolization (PVE) in hypertrophying the nonembolized lobe of patients with either normal or abnormal liver parenchyma and its effect upon portal pressure were examined to identify the patient population for whom this approach is most suited. METHODS: The study population included 43 patients undergoing major hepatectomy after PVE. Patients were divided into 2 groups according to their liver parenchyma: 17 patients with normal liver parenchyma (N group) and 26 patients with damaged liver parenchyma due to viral hepatitis (D group). We calculated the correlation between volumetric increases in the nonembolized (left) lobe after PVE (hypertrophic ratio = post-PVE left lobe volume/pre-PVE left lobe volume) using computed tomography volumetry before and 2 weeks after PVE. Clinical parameters also were examined to identify those parameters modifying the hypertrophic ratio in each group, and changes in portal pressure by PVE and the subsequent hepatectomy were recorded. Finally, by comparing patients with or without postoperative liver failure after hepatectomy, the influence of the hypertrophic ratio and portal pressure on the outcome of subsequent hepatectomy was examined. RESULTS: The hypertrophic ratio was 1.34 +/- 0.23 in the N group, and 1.25 +/- 0.21 in the D group. This difference was not significant. Multiple regression analysis revealed that the parenchymal volumetric rate of the right lobe (PVR) in the D group and both PVR and prothrombin time in the N group were independent parameters predicting the hypertrophic ratio. The portal pressure increased immediately after PVE and was similar in both groups to levels after hepatectomy. Six patients in the D group experienced postoperative liver dysfunction. In 5 of these 6 patients, the hypertrophic ratio was below 1.2, and the portal pressure was higher than that in patients without liver dysfunction. CONCLUSIONS: PVE induces hypertrophy of the nonembolized lobe of both abnormal and normal liver parenchyma, and the effect was predictable. Postoperative liver failure appeared to be more severe in patients having a lower hypertrophic ratio and higher portal pressure in abnormal liver parenchyma, however. PVE also may have diagnostic use in predicting portal pressure after hepatectomy, which may be associated with surgical outcome.

Evaluation of liver function for the application of preoperative portal vein embolization on major hepatic resection.

BACKGROUND/AIMS: Although preoperative portal vein embolization has been employed for hepatectomy to increase the safety of the surgery, patient selection criteria for hepatectomy following portal vein embolization have still not been established. In this study liver functional tests before and after portal vein embolization were evaluated in order to determine their influence on the outcome of subsequent hepatectomy and the prognostic potential of this approach. METHODOLOGY: Forty-five patients, who had undergone major hepatic resection after embolizing the right portal branch, were divided into the following 3 groups according to their postoperative course: complication(-), complication(+), and liver failure group. Clinical, analytical, and hemodynamic parameters obtained before and after portal vein embolization were compared between the three groups. RESULTS: Significant differences were found between the complication(-) group and the liver failure group for 8 factors, and statistically significant cut-off points distinguishing the liver failure group could be determined. Based upon values measured before PVE these were: 1) portal pressure > 16 cmH2O; 2) pre-PVE serum cholinesterase < 160 U/L; 3) pre-PVE serum hyaluronate > 130 ng/mL. Based on values measured after PVE they were: 1) a hypertrophic ratio of the left lobe < 1.21; 2) post-PVE ICGR15 (%) > 16%; 3) a portal pressure measured immediately after PVE > 25 cmH2O; 4) post-PVE serum cholinesterase < 160 U/L; 5) post-PVE serum hyaluronate > 160 ng/mL. Discriminant function analysis in a stepwise manner showed that the portal pressure and serum levels of hyaluronate measured before and after portal vein embolization were the most useful in prediction of the outcome of the following hepatectomy. CONCLUSIONS: Patients whose data match the above criteria before portal vein embolization should be excluded as candidates for major hepatic resection with portal vein embolization. Even after portal vein embolization in patients whose data match post-portal vein embolization criteria major hepatic resection may have to be abandoned, or the extent of the hepatic resection reconsidered.

Colo-colic intussusception associated with Henoch-Schönlein purpura in adults.

Henoch-Schönlein purpura (HSP) is often seen in childhood and is a self-limiting illness, and complication with intussusception is rare in adults. The case is reported of a 74-year-old man who was diagnosed with intussusception with HSP by ultrasonography on day of admission. Conservative therapy was started. However, his abdominal symptoms worsened, so he underwent laparotomy 3 days after admission. Histological study of the resected specimens demonstrated necrosis in the intussuscepted colon induced by HSP vasculitis. Bowel necrosis with intussusception in adult HSP is rare and might easily be overlooked. Thus special attention should be paid to gastrointestinal manifestations and, in an abdominal emergency, timely surgical intervention is life-saving.

Evaluation of the effect of age on functioning hepatocyte mass and liver blood flow using liver scintigraphy in preoperative estimations for surgical patients: comparison with CT volumetry.

BACKGROUND: The effect of age on functioning hepatocyte mass and liver blood flow was examined using (99m)Tc-galactosyl-human serum albumin (GSA) liver scintigraphy in patients with liver tumors awaiting surgery. MATERIALS AND METHODS: Seventy-two patients with liver tumors, but normal liver parenchyma, were included in this study; patients with compromised hepatic blood flow as a result of vascular invasion or thrombus were excluded. The liver volume, calculated liver volume, and liver blood flow index (K value) were preoperatively determined by liver scintigraphy using GSA. These three parameters and liver volume measured by computed tomography volumetry (CT-LV) and the standard liver volume (ST-LV), calculated from the patient's body surface area, were examined for correlations with the patient's age. The K value was compared with the indocyanine green dye retention rate, and both sets of results were examined for correlation with the patient's age. RESULTS: Both the CT-LV and the ST-LV decreased with age, resulting in an unchanged CT-LV/ST-LV ratio with aging. The liver volume and calculated liver volume measured by scintigraphy both decreased with age, even when body size was taken into account. Therefore, in elderly patients, the liver was not morphologically smaller, but the hepatocyte mass in the liver decreased. Furthermore, liver blood flow per unit of functional liver volume determined from the blood flow index did not change with age. CONCLUSIONS: These results, suggesting a discrepancy between liver volume estimated by CT and actual functioning hepatocyte volume in the elderly, may have a critical impact on preoperative liver functional reserve evaluation prior to hepatic resection in elderly patients.

Local expression of tumor necrosis factor-alpha and interleukin-10 on wound healing of intestinal anastomosis during endotoxemia in mice.

BACKGROUND: This study aimed to evaluate the integrity of anastomotic wound healing after digestive surgery under septic conditions and define the participation of local expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) around the anastomotic segment. MATERIALS AND METHODS: Experimental animals were divided into lipopolysaccharide (LPS) and control groups, which had either LPS or normal saline solution injected into the peritoneal cavity 24 h before transection and anastomosis of the colon. Anastomotic bursting pressure (ABP) and tissue hydroxyproline concentration (HP) were measured as indicators of wound healing. Immunohistochemical staining for TNF-alpha and IL-10 on tissue samples obtained from the anastomotic segment were examined 1, 6, and 24 h after the operation. The reactive cells were counted under light microscopy. RESULTS: ABP and HP were significantly lower in the LPS group than in the control group 7 days after surgery. In the LPS group, TNF-alpha expression increased about threefold over that in the control group 1 h after the operation. TNF-alpha-reactive cells were observed until 24 h after the operation in the LPS group, but not in the control group. On the other hand, IL-10 was not expressed in the control group during the observed period, whereas IL-10 was observed 24 h after the operation in the LPS group. CONCLUSIONS: It is suggested that anastomotic wound healing was impaired after the digestive surgery in animals treated with intraperitoneal LPS, and that local expression of TNF-alpha and IL-10 at the anastomotic site acts as an inhibitory factor in the wound healing process.

Hepatic resection for metastatic tumors from gastric cancer.

OBJECTIVE: To assess the surgical results and clinicopathologic features of hepatic metastases from gastric adenocarcinoma to identify patients with a better probability of survival. SUMMARY BACKGROUND DATA: Many studies have reported the benefit of hepatic resection for metastatic tumors from colorectal cancer. However, indications for a surgical approach for gastric adenocarcinoma involving the liver have not been clearly defined. METHODS: Ninety (11%) of 807 patients with primary gastric cancer were diagnosed with synchronous (n = 78) or metachronous (n = 12) hepatic metastases. Of these, 19 underwent 20 resections intended to cure the metastatic lesion in the liver. The clinicopathologic features of the hepatic metastases in, and the surgical results for, the 19 patients were analyzed. RESULTS: The actuarial 1-year, 3-year, and 5-year survival rates after hepatic resection were, respectively, 77%, 34%, and 34%, and three patients survived for more than 5 years after surgery. Solitary and metachronous metastases were significant determinants for a favorable prognosis after hepatic resection. Pathologically, a fibrous pseudocapsule between the tumor and surrounding hepatic parenchyma was found in 13 of the 19 patients (68%). The presence of a peritumoral fibrous pseudocapsule and a well-differentiated histologic type of metastatic nodule were significant prognostic factors. Factors associated with the primary lesion were not significant prognostic determinants in patients who underwent curative resection of the primary cancer. CONCLUSIONS: Solitary and metachronous metastases from gastric cancer should be treated by a surgical approach and confer a better prognosis. A new prognostic factor, the presence of a pseudocapsule, may be helpful in defining indications for postoperative adjuvant treatment.

Lymphocytic infiltration surrounding liver metastases from colorectal cancer.

BACKGROUND AND OBJECTIVES: Tumor infiltrating lymphocytes (TILs) have been recognized as a tumor-host reaction in various primary neoplasms. Although several studies reported TILs surrounding metastatic liver tumors, to the authors' knowledge few evaluations of the clinical significance of such features in patients with colorectal liver metastases have been carried out. METHODS: Forty-one patients who underwent initial hepatic resection for liver metastases from colorectal cancer were studied. Lymphocytic infiltration surrounding metastatic liver tumor was graded as weak or dense according to the mean number of TILs from 10 high-power microscopic fields (< or =50 or >50/HPF). RESULTS: Dense lymphocytic infiltration between the metastatic tumor and hepatic parenchyma was seen in 18 of 41 patients (44%). Histologically, tumor invasion of the portal vein was rare in patients with dense TILs (12%) compared with patients with weak TILs (36%). Patients with dense TILs survived longer than patients with weak TILs after hepatic resection (P = 0.013). Multivariate analysis using the Cox proportional hazard model identified this pathological variable as a significant independent prognostic factor after hepatic resection. CONCLUSIONS: The extent of lymphocytic infiltration between the metastatic nodule and hepatic parenchyma may reflect host defensive activity in the liver and is closely related to prognosis in patients who underwent hepatic resection for liver metastases from colorectal cancer.