Late Recurrence Group Research Articles

Metabolic profiling study of early and late recurrence of hepatocellular carcinoma based on liquid chromatography-mass spectrometry

The objectives of this pilot study were to predict early postoperative recurrence in hepatocellular carcinoma (HCC) patients based on metabolic features and to explore the related metabolic disturbances. Liquid chromatography-mass spectrometry-based metabolic profiling was performed on the plasma of 18 late recurrent and 22 early recurrent HCC patients. Metabolic differences were found to be related to amino acid, bile acid, cholesterol, fatty acid, phospholipid and carbohydrate metabolism. Bile acids, steroids and fatty acids showed significant variation in the early recurrent HCC group compared to the late recurrence group. Decreased levels of polyunsaturated eicosapentaenoic acid, docosahexaenoic acid and linolenic acid were found to be specific metabolic features for early recurrence. With the combination of methionine, GCDCA and cholesterol sulfate, 85% of the early recurrent HCCs can be predicted correctly with the corresponding area under the curve (AUC) equal to 0.95 in the training set, and 80% of the early recurrent HCCs can be predicted correctly with the corresponding AUC equal to 0.91 in the test set.

Early Recurrence After Liver Resection for Colorectal Metastases: Risk Factors, Prognosis, and Treatment. A LiverMetSurvey-Based Study of 6,025 Patients

The aims of this study were to assess the risk of early recurrence after liver resection for colorectal metastases (CRLM) and its prognostic value; identify early recurrence predictive factors; clarify the effect of perioperative chemotherapy on its occurrence; and elucidate the best early recurrence management. Patients of the LiverMetSurvey registry who underwent complete liver resection (R0/R1) between 1998 and 2009 were reviewed. Early recurrence was defined as any recurrence that occurred within 6 months after resection. A total of 6,025 patients were included; 2,734 (45.4 %) had recurrence, including 639 (10.6 %) early recurrences. Early recurrence was mainly hepatic (59.5 vs. 54.4 % for late recurrences; p = 0.023). Independent risk factors of early recurrence were: T3-4 primary tumor (p = 0.0002); synchronous CRLM (p = 0.0001); >3 CRLM (p < 0.0001); 0-mm margin liver resection (p = 0.003); and associated intraoperative radiofrequency ablation (p = 0.0005). Response to preoperative chemotherapy (complete/partial) and administration of adjuvant chemotherapy reduced early recurrence risk (p = 0.003 and p < 0.0001, respectively). Intraoperative ultrasonography reduced hepatic early recurrence rate (p = 0.025). Early recurrence negatively affected prognosis: 5-year survival 26.9 versus 49.4 % for the late recurrence group (p < 0.0001, median follow-up 34.4 months). Overall, 234 (36.6 %) patients with early recurrence underwent re-resection. These patients had survival rates higher than non-re-resected patients (5-year survival 47.2 vs. 8.9 %; p < 0.0001) and similar to re-resected patients for late recurrence (48.7 %). Chemotherapy before early recurrence resection improved later survival (5-year survival 61.5 vs. 43.7 %; p = 0.028). Early recurrence risk is enhanced for extensive disease after poor preoperative disease control and inadequate surgical treatment, but is reduced after adjuvant chemotherapy. Although early recurrence negatively affects prognosis, re-resection may restore better survival. Chemotherapy before early recurrence resection is advocated.

Comparison of clinicopathological characteristics and prognosis between early and late recurrence after curative surgery for colorectal cancer

BackgroundDespite curative surgery for colorectal cancer, some patients experience tumor recurrence. Whether early recurrence is associated with a shorter postrecurrence survival period compared with late recurrence remains unknown. MethodsA total of 395 patients with tumor recurrence after curative surgery for colorectal cancer were enrolled and divided into early (<3 years) and late (≥3 years) recurrence groups. Clinicopathologic characteristics, recurrence patterns, and postrecurrence survival were compared. ResultsFor stage I and II colorectal cancer, patients with T4 lesions tended to experience early recurrence. For stage III colorectal cancer, early recurrence was more common in patients with N2 disease. Patients with older age, mucinous-type tumors, poorly differentiated histology, the presence of lymphovascular invasion, or multiple site recurrence tended to die <2 years after recurrence. Median postrecurrence survival was similar for the 2 groups. Patients undergoing resection of liver or lung metastases demonstrated longer postrecurrence survival compared with those who did not undergo resection. ConclusionsCompared with late recurrence, early recurrence does not indicate a worse outcome in colorectal cancer.

Predicting late recurrence in surgically treated patients with Cushing's disease

Cushing's disease (CD) has an uncertain prognosis because patients achieving remission after transsphenoidal pituitary neurosurgery (TSS) may relapse. We aimed to identify factors predicting relapse, focusing on desmopressin (DDAVP) and corticotropin-releasing hormone (CRH) tests after surgery. Fifty-seven patients with CD (mean age 36 years) after TSS experienced remission (24 cases), late relapse (LR) (15 cases), or persistent disease (18 cases). The median time to relapse was 40 months. ACTH levels increased after both DDAVP and CRH stimulation, with a significantly higher response in the late recurrence group, showing this to be an indicator of increased risk of relapse. In the logistic regression model, a rise in ACTH >9 pg/ml after DDAVP and >36·7 pg/ml after CRH showed a sensitivity of 93% and 73%, respectively, a specificity of 82% and 76% in LR group. The area under the curve was 0·91 for DDAVP, 0·80 for CRH and 0·95 for DDAVP+CRH test, i.e. the combined tests performed better than each test alone, but not to a statistically significant degree. A response to both tests resulted in a positive predictive value (PPV) of 100%, while no response to either test in a negative predictive value (NPV) of 100%. ACTH hyper-responsiveness to DDAVP stimulation proved a valuable indicator of relapsing patients with high sensitivity and specificity; in selected cases when a clear high increment of ACTH level is not evident, the CRH test might be used as additional tool to confirm the risk of future relapses.

Late Recurrence in Melanoma: Clinical Implications of Lost Dormancy

For patients with melanoma, if there has been no recurrence of disease 10 years after initial treatment, additional disease is believed to be very unlikely. However, such late recurrences are known to occur. The frequency of this phenomenon and its clinical significance are not well characterized due to the difficulty in obtaining relevant data. We examined a large, mature, institutional database to evaluate late recurrence. The late recurrence cohort was defined as having a disease-free interval of 10 or more years after potentially curative treatment and was compared with an early recurrence cohort recurring within 3 years. Actuarial late recurrence frequency and factors associated with late recurrence were examined. Post-recurrence overall and melanoma-specific survival and prognostic variables were analyzed. Among all patients, 408 exhibited late recurrence (mean disease-free interval 15.7 years). For patients who received primary treatment at our institution with 10 or more years follow-up, 327 of 4,731 (6.9%) showed late recurrence. On an actuarial basis, late recurrence rates were 6.8% and 11.3% at 15 and 20 years, respectively, for those with no recurrence at 10 years. Late recurrence was associated with both tumor (thin, non-ulcerated, non-head/neck, node negative) and patient (younger age, less male predominant) characteristics. Multivariate analysis confirmed younger age, thinner and node negative tumors in the late recurrence group. Late recurrences were more likely to be distant, but were associated with better post-recurrence survival on univariate and multivariate analyses. Late melanoma recurrence is not rare. It occurs more frequently in certain clinical groups and is associated with improved post-recurrence survival.

1913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced (II)1 Apr 20131913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA Takehiro Sejima, Hideto Iwamoto, Toshihiko Masago, Shuichi Morizane, Akihisa Yao, Tadahiro Isoyama, and Atsushi Takenaka Takehiro SejimaTakehiro Sejima Yonago, Japan More articles by this author , Hideto IwamotoHideto Iwamoto Yonago, Japan More articles by this author , Toshihiko MasagoToshihiko Masago Yonago, Japan More articles by this author , Shuichi MorizaneShuichi Morizane Yonago, Japan More articles by this author , Akihisa YaoAkihisa Yao Yonago, Japan More articles by this author , Tadahiro IsoyamaTadahiro Isoyama Yonago, Japan More articles by this author , and Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2332AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine the role of the immune system in patients with metastatic renal cell carcinoma (RCC), we investigated the relationship between metastatic characteristics, immunological parameters including expression of Fas ligand (FasL) in nephrectomized tumors and patient prognosis. METHODS 1) Stratification into three groups; forty-five patients with metastatic RCC had undergone nephrectomy followed by Interferon (IFN) α treatment were stratified into three groups based on the time of metastasis occurrence (i.e., at first presentation [METS at FP, n = 14], within five years of nephrectomy [early recurrence, n = 17] and five years after nephrectomy [late recurrence, n = 14]). Patient prognosis (i.e., progression-free survival [PFS] during IFN α treatment and overall survival [OS] from metastasis occurrence) and immunological parameters (i.e., neutrophil / lymphocyte ratio [NLR], serum albumin and FasL expression in RCC) were compared among the groups. FasL expression was analyzed by immunohistochemistry (IHC) and mRNA quantification. 2) Stratification into two groups; forty-five patients were stratified into two groups based on FasL positivity as determined by IHC. Patient prognosis and the aforementioned immunological parameters were compared between the groups. RESULTS 1) The patients in the late recurrence group had significantly longer PFS during IFN α treatment and OS compared to those in the other two groups. The NLR was significantly lower in the late recurrence group than in the METS at FP (P < 0.0001) and early recurrence (P = 0.0043) groups. The FasL mRNA expression was significantly lower in the late recurrence group than in the METS at FP (P = 0.0016) and early recurrence (P = 0.0076) groups. 2) The PFS during IFN α treatment was significantly longer in the FasL-negative (n = 18; median 18.4 mo.) than in the FasL-positive (n = 27; median 11.6 mo.) group (P = 0.0475). The NLR was significantly lower in the FasL-negative than in the FasL-positive group (P = 0.0085). CONCLUSIONS Our results suggest that strong host immune activity as determined by the effectiveness of IFN α treatment and OS in metastatic RCC is associated with delayed occurrence of metastasis, high peripheral blood lymphocyte activity and low FasL expression in nephrectomized tumors. “FasL counter attack” may occur in metastatic RCC; that is, FasL on the surface of circulating tumor cells binds to the Fas receptor on peripheral blood lymphocytes and diminishes the effectiveness of IFN α treatment. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e784-e785 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takehiro Sejima Yonago, Japan More articles by this author Hideto Iwamoto Yonago, Japan More articles by this author Toshihiko Masago Yonago, Japan More articles by this author Shuichi Morizane Yonago, Japan More articles by this author Akihisa Yao Yonago, Japan More articles by this author Tadahiro Isoyama Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Factors Affecting the Time to Recurrence After Radical Nephrectomy for Localized Renal Cell Carcinoma

PurposeThe objective of this study was to determine the factors affecting the time to recurrence after radical nephrectomy for localized renal cell carcinoma.Materials and MethodsWe retrospectively evaluated 321 patients who received radical nephrectomies for localized renal cell carcinoma (pT1a-pT2b N0M0). Of 29 patients with disease recurrence, 9 had recurrence more than 5 years after radical nephrectomy. We evaluated the clinicopathological factors, with the use of a retrospective study design.ResultsTumor necrosis was statistically different between the late recurrence group and the recurrence free group (Fisher exact test, p=0.046). Hematuria at diagnosis (chi-square test, p=0.045) was statistically significant in early recurrence. In the univariate logistic regression analysis, tumor necrosis (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.106 to 19.379; p=0.036) and pT stage>1 (OR, 7.232; 95% CI, 1.727 to 30.280; p=0.007) were risk factors of late recurrence. In the multivariable logistic regression analysis, pT stage>1 (OR, 7.143; 5% CI 1.706 to 29.912, p=0.007) was associated with late recurrence. Regarding early recurrence, initial symptoms at diagnosis and pathologic T stage>1 were statistically significant in both univariate and multivariable logistic regression analysis. In terms of recurrence site, patients with late recurrence tended to have unusual metastasis sites other than lung, liver or bone (chi-square test, p=0.012).ConclusionsThese data suggest that tumor necrosis may affect late disease recurrence. Patients with initial symptoms and hematuria at diagnosis are vulnerable to recurrence in a shorter period after nephrectomy. Patients with late recurrence showed a tendency to have unusual metastasis site other than lung, liver or bone.

Cause of Very Late Recurrence of Atrial Fibrillation or Flutter After Catheter Ablation for Atrial Fibrillation

The major mechanism underlying the early recurrence of atrial fibrillation (AF) after ablation is mainly reconnection of the isolated pulmonary vein (PV); however, the mechanism responsible for very late recurrence (VLR) has not been fully elucidated. The purpose of the present study was to investigate the mechanism underlying VLR. The study population included 150 consecutive patients with AF who underwent a second session of catheter ablation because of recurrence. We divided them into 2 groups according to the point of initial AF recurrence: the late recurrence group (LR group, initial recurrence 3 to 12 months after ablation, n= 124) and the VLR group (initial recurrence >12 months after ablation, n= 26). We identified PVs with ectopic foci (trigger PVs) in the first procedure and checked their electrical reconnection in the second procedure. The prevalence of PV reconnection and trigger PV reconnection were significantly lower in the VLR group than in LR group (LR vs VLR, 90% vs 69% and 48% vs 27%, p= 0.007 and p= 0.045, respectively). In the VLR group, left ventricular systolic and diastolic function were significantly worse than in the LR group, and more patients in the VLR group required non-PV trigger ablation in the second session than did those in the LR group (30% vs 54%, p= 0.034). In conclusion, electrical PV reconnection contributed less to VLR than to LR. Progression of the AF substrate might be an important mechanism responsible for VLR.

Cardioembolic Stroke is Frequent in Late Recurrence After Transient Ischemic Attack

Transient ischemic attack (TIA) is often followed by a stroke episode. Differences between early and late recurrent stroke, however, have not been elucidated. We enrolled 133 consecutive patients with acute ischemic stroke who presented to our hospital and had previously been diagnosed with TIA. They were divided into 5 groups according to the interval between TIA and subsequent stroke: <48 hours (group 1); 48 hours to 1 week (group 2); 1 week to 1 month (group 3); 1 month to 3 months (group 4); and >3 months (group 5). Patients who underwent recurrent stroke within and after 1 week subsequent to TIA (the early and late recurrence groups, respectively) were compared with regard to clinical findings. Of the 133 patients, 46 (34.6%) were in group 1, 29 (21.8%) in group 2, 23 (17.3%) in group 3, 18 (13.5%) in group 4, and 17 (12.8%) in group 5. Most of the noncardioembolic strokes were observed shortly after TIA, while the percentage of cardioembolic stroke remained high even after long post-TIA periods. The prevalence of atrial fibrillation (AF) was higher in the late recurrence group than in the early recurrence group (41.4% v 24.0%, P = .033). Among 42 patients with AF, 12 (28.6%) were newly diagnosed at the time of stroke. The frequency of cardioembolic stroke did not decline as time after TIA passed. More than one quarter of AF patients had been asymptomatic before stroke, suggesting the need for repeated examinations to detect AF in patients with TIA of unknown etiology.

Abstract 3396: Predictive value of metastatic lymph node ratio in diagnosis of recurrence after surgical resection of gastric cancer

Abstract Peritoneal meatastasis is the most important pattern in postoperative recurrence of gastric cancer. The purpose of this study was to investigate the predictive factors of peritoneal recurrence in gastric cancer patients who underwent surgical resection. We retrospectively analyzed clinical data of 137 consecutive patients diagnosed with peritoneal recurrence after curative gastrectomy at Department of Osaka City University Hospital. We evaluated association of clinicopathological features with relapse free survival rate. Parameters analyzed in this study included age, sex, tumor diameter, histological type, tumor infiltration, number of lymph node metastasis, TNM stage, lymphatic invasion, venous invasion, and metastatic lymph node ratio (MLR). Median survival time of entire patients was 12 months and mean MLR was 34%. For statistical analysis, we divided patients into two groups based on relapse free survival time. 78 patients who had peritoneal recurrence within one year after gastrectomy were defined as early recurrence group. The remaining 59 patients were stratified to late recurrence group. In comparison of both groups, univariate analysis showed statistically significant predictive factors associated with recurrence, for example, peritoneal lavage cytology, lymphatic invasion, tumor diameter, number of lymph node metastasis, and MLR. In multivariate analysis, MLR was identified as an independent predictive factor. Also the patients with 20% or higher MLR had poorer prognosis in overall survival. We demonstrated that lymph node metastasis was associated with peritoneal recurrence. Our findings suggested that MLR should be considered for postoperative adjuvant therapy to impede progression of peritoneal metastasis for gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3396. doi:1538-7445.AM2012-3396

Abstract 2739: Cardioembolic Stroke Is Frequent in the Late Recurrence After Transient Ischemic Attack

Background The high risk of stroke after transient ischemic attack (TIA) has been widely recognized, although the differences of clinical characteristics between early and late recurrent stroke were not well-known. Materials and methods The subjects were 133 consecutive ischemic stroke patients who were admitted to our hospital within one week of onset, and had previously diagnosed as “definite TIA” by trained stroke neurologists. They were divided into five groups according to the interval between prior TIA and subsequent stroke; (1) within 48 hours, (2) 48 hours to 1 week, (3) 1 week to 1 month, (4) 1 month to 3 months, and (5) after 3 months (group 1 to 5, respectively). Then, we compared clinical characteristics and prognosis between the patients who presented recurrent stroke within and after 1 week subsequent to TIA (early recurrence group and late recurrence group, respectively). Results Of the 133 acute stroke patients (mean age 69.9 years, male 66.9%), 46 (34.9%) were in group 1, 28 (21.2%) in group 2, 23 (17.4%) in group 3, 18 (13.6%) in group 4, and 17 (12.9%) in group 5. As to stroke subtypes, most of the non-cardioembolic strokes were frequently observed shortly after TIA, while the percentage of cardioembolism remained high even the time from prior TIA passed ( Figure ). The prevalence of atrial fibrillation (Af) was higher (39.7% vs. 21.3%, P =0.034), and dyslipidemia was lower (41.4% vs. 64.0%, P =0.014) in the late recurrence group than in the early recurrence group. The percentages of patients with hypertension, diabetes mellitus, and higher ABCD 2 score (≥3 or ≥5) were similar in both groups. Among 42 patients with Af, 14 (33.3%) were premorbid, 16 (38.1%) were diagnosed when TIA presented, and 12(28.6%) were diagnosed when stroke presented. In the late recurrence group, 37/58 patients (63.8%) had a poor outcome (modified Rankin Scale ≥3) at 3 month of stroke onset, significantly higher than the 29/75 (38.7%) patients in the early recurrence group ( P =0.005). Conclusions The frequency of cardioembolic stroke dose not decline during the time course after TIA, while most of the non-cardioembolic stroke recur early after TIA. This might be responsible for the poorer functional outcome in late recurrent stroke. More than quarter of Af patients had been asymptomatic before stroke, which suggests the need for repeated examinations to detect Af in patients with TIA of unknown etiology.

Activation of c‐Jun N‐terminal kinase in non‐cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. Hepatic resection is the mainstay of curative treatment for early stage HCC. Although c-Jun N-terminal kinase (JNK) activation contributes to hepatocyte proliferation and HCC development in mice, the extent of involvement of JNK in human HCC development is unknown. The aim of this study is to assess the predictive value of JNK for postoperative recurrence in HCC. From April 2005 to March 2008, 159 patients underwent curative resection for HCC. From the 159 patients, 20 patients each matched for age, gender and etiology were registered as three groups: (i) without recurrence (no recurrence group), (ii) with recurrence within one year after surgery (early recurrence group), and (iii) with recurrence at one year or more after surgery (late recurrence group) (a cross-sectional control study). We investigated factors contributing to postoperative early and late phase recurrence. Multivariate analysis using a Logistic regression model showed that JNK activity in non-cancerous liver tissue was correlated with postoperative late recurrence. (P = 0.02, odds ratio; 5.79, 95% confidence interval [CI]; 1.33-25.36). JNK activity in non-cancerous liver tissue is considered as a reliable predictive biomarker for post-operative recurrence in HCC.

The significant immunological characteristics of peripheral blood neutrophil-to-lymphocyte ratio and Fas ligand expression incidence in nephrectomized tumor in late recurrence from renal cell carcinoma

ObjectiveIn order to characterize the significance of immune system function in patients with advanced renal cell carcinoma (RCC), we investigated the interactive relationships among the following parameters: metastatic characteristics, expression of Fas ligand (FasL) in nephrectomized specimens, immunological parameters, and patient's prognosis. Materials and methodsThirty-five patients with advanced RCC were stratified into 3 groups according to the characteristics of metastasis timing, at first presentation (mFP), within 5 years of nephrectomy (early-recurrence), after 5 years (late-recurrence). Immunological parameters [hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio (NLR), serum albumin, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and Charlson Comorbidity Index], FasL expression in RCC, and patient prognosis from occurrence of metastasis were compared among the groups. Thirty-five patients were also stratified into 2 groups according to FasL positivity and individual parameters. Patient's prognosis and the remaining immunological parameters were compared between groups. ResultsThe NLRs of the late-recurrence group were significantly lower than those of the mFP (P = 0.0004) and early-recurrence (P = 0.013) groups. The FasL mRNA positivity of the late-recurrence group was significantly lower than those of the mFP (P = 0.001) and early-recurrence (P = 0.0277) groups. The prognosis of the late-recurrence group was significantly better than that of the early-recurrence group (P = 0.0255). NLRs were significantly lower in the FasL-negative group than in the -positive group (P = 0.0182). The cause-specific survival rates of the ECOG PS 0 group were significantly higher than that of the ECOG PS > 0 group (P < 0.0001). ConclusionsOur results suggest the associations of the prognosis in advanced RCC with peripheral blood NLR and FasL expression in nephrectomized tumor. The characteristics of lower values of NLR and FasL expression positivity in late-recurrence compared with other metastatic timings suggest strong host immune activity, and may imply relatively long survival. On the other hand, elucidation of the patient's general condition obtained not only by chemical data but also by ECOG PS is crucial in the management of patients with advanced RCC.

Late Recurrence of Hepatocellular Carcinoma after Liver Transplantation

BackgroundLong-term survival of patients with hepatocellular carcinoma (HCC) after liver transplantation is affected mainly by recurrence of HCC. There is the opinion that the chance of recurrence after 2 years post-transplantation is remote, and therefore lifelong surveillance is not justified because of limited resources. The aims of the present study were to determine the rate of late HCC recurrence (≥2 years after transplantation) and to compare the long-term patient survival outcomes between cases of early recurrence (<2 years after transplantation) and late recurrence.PatientsA total of 139 adult HCC patients having liver transplantation during the period from July 1994 to December 2007 were included in the analysis. The median follow-up period was 55 months. Thirty-two patients received deceased-donor grafts and 107 received living-donor grafts.ResultsHepatocellular carcinoma recurrence occurred in 24 (17.3%) patients, among them 22 (86%) had living-donor grafts and 7 (5%) developed late recurrence. Patients in the early recurrence group and patients in the late recurrence group had comparable demographics and disease pathology. The former group, when compared with the latter, had significantly worse overall survival at 3 years (13.3 versus 100%) and 5 years (6.67 versus 71.4%) (log-rank test; p < 0.001).ConclusionsBoth early recurrence and late recurrence of HCC after liver transplantation were not uncommon, mostly detected at a subclinical stage. Regular and long-term surveillance with imaging and blood tests is essential for early detection.

Risk Factors, Prognosis, and Management of Early and Late Intrahepatic Recurrence After Resection of Primary Clear Cell Carcinoma of the Liver

Primary clear cell carcinoma of the liver (PCCCL) is an uncommon variant of hepatocellular carcinoma (HCC). The prognostic factors influencing its recurrence and survival are not clarified. This study is to evaluate the predictive factors, the therapy, and prognosis of intrahepatic recurrences after resection of PCCCL. A total of 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed. Intrahepatic recurrences were classified into early (≤1 year) and late (>1 year) recurrences. The 1-, 3-, and 5-year overall survival (OS) rates for PCCCL patients were significantly better than those of HCC patients (P = .001). Serum a-fetoprotein (AFP) level, tumor size, liver cirrhosis, and vascular invasion were independent risk factors for both OS and disease-free survival (DFS) of PCCCL. Early and late intrahepatic recurrences developed in 28 patients and 71 patients, respectively. In multivariate analysis, ALT level and vascular invasion were independent risk factors for early recurrence, whereas age was the only significant risk factor for late recurrence. OS of late-recurrence group was significantly better than that of early-recurrence group (P = .001), and re-resection rate was higher in late than in early-recurrence group (P = .04). The 1-, 3-, and 5-year OS of patients with recurrence who received curative treatment was comparable to those who never had tumor recur (P = .71). PCCCL has a better prognosis and tends to recur later than HCC. Early and late recurrences of PCCCL are linked to different predictive factors. The time to recurrence and feasibility of curative treatment are the best determinants for the prognosis.

Clinicopathologic Characteristics of Gastric Cancer Patients according to the Timing of the Recurrence after Curative Surgery

PurposeThere are few studies that have focused on the predictors of recurrence after gastrectomy for gastric carcinoma. This study analyzed the patients who died of recurrent gastric carcinoma and we attempted to clarify the clinicopathologic factors that are associated with the timing of recurrence.Materials and MethodsFrom June 1992 to March 2009, 1,795 patients underwent curative gastric resection at the Department of Surgery, Hanyang University College of Medicine. Among them, 428 patients died and 311 of these patients who died of recurrent gastric carcinoma were enrolled in this study. The clinicopathologic findings were compared between the 72 patients who died within one year after curative gastrectomy (the early recurrence group) and the 92 patients who died 3 years after curative gastrectomy (the late recurrence group).ResultsCompared with the late recurrence group, the early recurrence group showed an older age, a more advanced stage, a poorly differentiated type of cancer and a significantly higher tendency to have lymphatic invasion, vascular invasion and perineural invasion.Especially in the gastric cancer patients with a more advanced stage (stage III and IV), the early recurrence group was characterized by a significantly higher preoperative serum carcino embryonic antigen level, perineural invasion and a relatively small number of dissected lymph nodes.ConclusionsThe clinicopathologic characteristics of recurrent gastric cancer are significantly different according to the stage of disease, and even in the same stage. For the early detection of recurrence after curative surgery, it is important to recognize the clinicopathological factors that foretell a high risk of recurrence. It is mandatory to make an individualized surveillance schedule according to the clinicopathologic factors.

High TSC22D3 and low GBP1 expression in the liver is a risk factor for early recurrence of hepatocellular carcinoma

Recurrence after liver resection for hepatocellular carcinoma (HCC) is a major clinical problem, and prognostic markers for recurrence are urgently required. For 390 HCC cases, segmented linear regression analysis with two segments was performed, and the interval for the early and late recurrence groups was partitioned at the crosspoint (676 days). We investigated whether gene expression in non-tumorous tissues of remnant liver from 39 hepatitis C virus-positive HCC cases may be associated with early recurrence of this disease. By microarray analysis, 21 genes were identified as candidate recurrence-associated genes. Further gene expression analysis was performed, and the localization and expression of the gene products of these candidate genes were immunohistochemically evaluated. Low expression of the GBP1 gene and high expression of the TSC22D3 gene were significantly (both P=0.04) associated with the risk of early recurrence. Through backward step-wise multivariate logistic regression analysis for the 21 candidate genes, high expression of GBP1 reduced [odds ratio (OR)=0.20; 95% confidence interval (CI) 0.06-0.73, P=0.02] and high expression of TSC22D3 increased the risk of early recurrence (OR=19.6; 95% CI 1.14-337.2; P=0.04). Immunohistochemical analysis revealed that hepatocytes showed strong membranous expression for GBP1 in the late recurrence group, but weak membranous expression for GBP1 in the early recurrence group. TSC22D3 was frequently expressed in lymphocytes and in a few hepatocytes in tissues of the early recurrence group. Our observations suggest that the combination of the high expression of the TSC22D3 gene and low expression of the GBP1 gene in the non-tumorous tissue of the remnant liver is significantly associated with early recurrence after surgical resection of HCC.

Predictors of Timing and Patterns of Recurrence after Curative Resection for Gastric Cancer

Aims: The aim of the study was to characterize recurrence patterns and identify predictors of recurrence after curative resection. Methods: Of 2,786 patients that underwent curative resection for gastric cancer from 2001 to 2006 at the Korean National Cancer Center, 439 (15.8%) experienced recurrence. Patterns of recurrence, clinicopathological characteristics, and therapeutic modalities were compared between 251 patients who had recurrence within 1 year (the early recurrence group) and 188 patients who had recurrence after more than a year (the late recurrence group). Multivariate analysis was performed to identify independent factors associated with the timing of recurrence. Results: In the early recurrence group, the most common pattern was hematogenous metastasis, and in the late recurrence group, the most common pattern was locoregional and peritoneal recurrence. The early recurrence group was characterized by a larger tumor, frequent lymph node (LN) metastasis, and venous, and perineural invasion. Multivariate analysis showed that LN metastasis and venous invasion were independent predictors of early recurrence. Median survival after recurrence was significantly shorter in the early recurrence group (p < 0.001). Conclusion: Hematogeneous metastasis was more common in the early recurrence group and LN metastasis and venous invasion were independent predictors of the timing of recurrence.

Clinical and pathological evaluation of patients with early and late recurrence of colorectal cancer

To compare the characteristics of primary cancer between patients with early recurrence and those with late recurrence of colorectal cancer. Overall 535 patients with primary colorectal cancer were reviewed and of these 130 patients with demonstrated recurrence were evaluated. Of the 130 patients, 91 had early recurrence (less than 2 years after surgery) and 39 had late recurrence (2 years or more after surgery). The clinical and pathological characteristics of primary cancer in these two groups were compared. The rate of late recurrence was 30% of total recurrences (39/130). On average, patients with early recurrence were younger than patients with late recurrence (mean age 48 vs 54 years, p = 0.027). Adjacent organ involvement and Dukes stage C was more prevalent in the early recurrence group than in the late group. The liver was the main site of distant recurrence in the early recurrence group (64% of distant recurrences), whereas bone and peritoneum were the most frequent sites of metastases in the late recurrence group (58%). In Dukes C colon cancer patients the disease-free interval was significantly longer in those who received both adjuvant therapies than in those who received either radiotherapy or chemotherapy or neither of them. This study showed that factors such as primary clinical signs, stage of primary tumor, and adjacent organ involvement are significant with respect to the time for recurrence of colorectal cancer. It is important to take these characteristics into account in patient care management after curative resection for colorectal cancer.

Early Recurrence of Papillary and Follicular Thyroid Carcinoma Predicts a Worse Outcome

The occurrence of recurrent papillary and follicular thyroid carcinomas is not unusual. Numerous studies have reported the association between risk factors of initial surgery and recurrence of papillary and follicular thyroid carcinomas. However, we do not have sufficient data to analyze the time of postoperative recurrence associated with therapeutic results and cancer mortality. We hypothesized that an early recurrence of papillary and follicular thyroid cancers implies a rapid growth of cancer resulting in high mortality rate. We conducted a retrospective study in a medical center in northern Taiwan. The investigation included 2148 cases of papillary and follicular thyroid carcinoma, including 325 recurrent cases during the period between 1977 and 2006. The studied cases were categorized into early or late recurrence groups. Cases with an early recurrence were defined as those in which recurrence occurred in the first year following thyroid surgery. Tumor size, radioactive iodide treatment, multifocality, and tumor-node metastasis stage were independent predictors of recurrence. After a mean follow-up of 8.7 +/- 0.1 years, death due to thyroid cancer was observed to occur in 105 (32.3%) recurrent cases. Among the 325 recurrent cases, early recurrence was detected in 185 cases, and late recurrence was detected in 140 cases. Early recurrence was mostly observed in older male patients; a high mortality rate was associated with these cases. Distant metastases were observed in about 80% of the cases in the early recurrence group, whereas localized metastases in the neck region were observed in more than half the cases in the late recurrence group. The percentage of patients with a non-disease-free status and distant metastases in the early recurrence group was higher than that in the late recurrence group. The 10-year disease-specific survival rates were 52.5% and 85.1% for the early and late recurrence groups, respectively. Early recurrent papillary and follicular thyroid carcinomas are associated with high mortalities. Tumor size and multifocality deserve consideration as indicators of recurrence. Therefore, patients whose primary follicular or papillary thyroid carcinoma has features associated with early recurrence should probably receive more aggressive initial treatment.