Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?

BACKGROUND/AIMS: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy. METHODOLOGY: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect. CONCLUSIONS: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

What is the optimal treatment in clinical stage T3N0M0 rectal cancer?

PURPOSE: Some previous studies suggested that certain rectal cancer patients with stage T3N0 and favorable features may be adequately treated with surgery and adjuvant chemotherapy. However, the optimal management of clinical (c) T3N0 rectal adenocarcinoma based on preoperative imaging is unclear. In this study, we aimed to determine the frequency of lymph node metastases in patients clinically staged as T3N0 rectal adenocarcinoma following preoperative chemoradiotherapy (CTR). METHODS: The medical records of 105 patients with clinico- imaging stage T3N0M0 rectal cancer who received preoperative CRT between 2004-2011 were retrospectively analyzed. Chemotherapy used concurrently with preoperative radiotherapy (RT) was protracted 5-fluorouracil (5FU) infusion. RESULTS: Twenty-seven percent of the patients clinically staged as T3N0 before preoperative CRT had pathological (p) lymph node involvement on surgical material. The rate of pathological lymph node involvement was 0% in pT1, 20% in pT2 , 35% in pT3 and 34% in pT4 patients. A significant association was demonstrated between pT stages and pN status (p=0.03). CONCLUSION: Our study demonstrated that the accuracy of preoperative imaging for staging rectal cancer is limited because at least 27% of the patients may have undetected lymph node involvement after preoperative CRT in surgical material.

Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer.

BACKGROUND: The study populations of previous preoperative chemoradiotherapy (pre-CRT) studies have consisted of mixed clinical stages, such as cT3-cT4 and/or cN positive. For this reason, it has not been possible to demonstrate whether pre-CRT is of benefit for individual subgroups. METHODS: The medical records of 137 rectal cancer patients with clinical stage T3, N0 disease who received either pre-CRT or postoperative chemoradiotherapy (post-CRT) between 2002 and 2011 were retrospectively analyzed. The regimen of pre-CRT consisted of slow fluorouracil (5FU) infusion and that of post-CRT consisted of bolus 5FU and leucovorin concurrent with radiation. RESULTS: Following pre-CRT, significant downstaging was achieved. However, administration of pre-CRT did not influence the type of surgical resection in tumours ≤5 cm distant from the anal verge (p = 0.14). Pathological complete response was achieved in 16 % of the patients in the pre-CRT group. The local recurrence rate (LRR) at 5 years was 5.7 % in the pre-CRT and 11.1 % in the post-CRT groups (p = 0.04). The distant recurrence rate (DRR) at 5 years was 76 % and 77 % in the pre-CRT and post-CRT groups, respectively (p = 0.1). Overall survival was similar in two groups (74.8 % vs. 75.3 %, p = 0.3). CONCLUSIONS: The treatment of stage T3, N0 rectal cancer patients with pre-CRT followed by surgery decreased LRR, but did not improve DRR or OS as compared with surgery followed by post-CRT in our patient cohort.

Is her-2 status in the primary tumor correlated with matched lymph node metastases in patients with gastric cancer undergoing curative gastrectomy?

BACKGROUND: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. MATERIALS AND METHODS: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). RESULTS: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05). CONCLUSIONS: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

The relation between pathological complete response and clinical outcome in patients with rectal cancer.

BACKGROUND/AIMS: Preoperative chemoradiotherapy (CRT) is the standard treatment modality in locally advanced rectal cancer. The primary aim was to correlate pathological complete response (pCR) with patient outcome, and the secondary objective was to identify predictive factors of pCR. METHODOLOGY: Patients with clinical stage II/III rectal cancer who received preoperative CRT between 2002 and 2010 were retrospectively studied.The median radiotherapy dose was 54 Gy (range, 45 to 64 Gy), and all patients received concurrent infusional 5-fluorouracil-based chemotherapy. RESULTS: Median follow-up time was 48.3 months (range, 24 to 96 months) and 51 months (range, 44 to 110 months) for no-pCR and pCR groups, respectively. Eighteen patients (18.6%) had pCR. The 5-year overall survival was 95% for patients with pCR and 74.8% in patients without pCR (p=0.009). The 5-year local relapse free survival was 87.5% and 95% for the no-pCR and pCR groups, respectively (p=0.09). The 5-year distant relapse free survival was 93% in pCR group and 79.8% in no-pCR group (p=0.02). The 5-year distant free survival was 94% and 66% in patients with and without pCR, respectively (p=0.017). The clinical T4 (p=0.043) and pretreatment carcinoembryonic antigen level (CEA) >5ng/mL (p=0.012) were significantly associated with a lower pCR rate. In the multivariate logistic regression analysis, pretreatment CEA level >5ng/mL (p=0.008) was the only independent factor associated with a lower pCR rate. CONCLUSIONS: Patients with pCR after preoperative CRT had a significantly improved outcome. Furthermore, the pretreatment CEA level was independently associated with pCR.

Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III 'Stop and Go' study results--a Turkish Oncology Group Trial.

OBJECTIVE: It was the aim of this study to evaluate maintenance therapy with bevacizumab + capecitabine following induction with bevacizumab + capecitabine + oxaliplatin (XELOX) versus bevacizumab + XELOX until progression as first-line therapy in metastatic colorectal cancer (mCRC). METHODS: Patients received either bevacizumab (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m(2) twice daily on days 1-14 + oxaliplatin 130 mg/m(2) on day 1 every 3 weeks) until disease progression (arm A) or the same doses of bevacizumab + XELOX for 6 cycles followed by bevacizumab + capecitabine until disease progression (arm B). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. RESULTS: One hundred and twenty-three patients were randomized. Treatment compliance was similar in both groups. Median PFS was significantly longer for arm B than for arm A (11.0 vs. 8.3 months; p = 0.002). There was no significant difference between the two arms for ORR (66.7 vs. 59.0%; p = 0.861) or median OS (23.8 vs. 20.2 months; p = 0.100). Tolerability was acceptable in both treatment arms; the most frequent grade 3/4 treatment-related adverse events (arm B vs. arm A) were fatigue (6.6 vs. 16.1%), diarrhoea (3.3 vs. 11.3%), anorexia (3.3 vs. 11.3%), and neuropathy (1.6 vs. 8.1%). CONCLUSIONS: Maintenance therapy with bevacizumab + capecitabine can be considered an appropriate option following induction bevacizumab + XELOX in patients with mCRC instead of continuation of bevacizumab + XELOX.

Is Helicobacter pylori a poor prognostic factor for HER-2 SISH positive gastric cancer?

BACKGROUND: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown. MATERIALS AND METHODS: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated. RESULTS: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes. CONCLUSIONS: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.

Are high initial CEA and CA 19-9 levels associated with the presence of K-ras mutation in patients with metastatic colorectal cancer?

In certain cell culture studies, significant CEA expression was observed in K-ras mutant cells. However, the relationship between high CEA levels and K-ras status has not been sufficiently investigated. In the present study, we aimed to determine the prognostic role of initial CEA and CA 19-9 values in metastatic colorectal cancer patients according to the status of K-ras. Between 2000 and 2010, a total of 215 patients with metastatic colorectal cancer who were treated and followed up in our oncology center were analyzed. Smokers were excluded from the study. The clinicopathological findings and initial CEA and CA19-9 values were determined. K-ras mutation analysis was performed using quantitative PCR evaluation of the DNA from the tumor tissues. Eighty-two patients (38.1 %) were female and 133 (61.9 %) were male, with a median age of 59 years (range 27-83). Based on tumor localization, 127 patients (59 %) were classified as colon cancer patients and 88 patients (41 %) were classified as rectal cancer patients. The majority of patients (83.3 %) had pure adenocarcinoma histology, while 36 cases (16.7 %) had mucinous adenocarcinoma. The initial CEA levels were detected to be high (>5 ng/mL) in 108 of the patients (50.2 %), while high levels of initial CA 19-9 (>37 ng/mL) were found in 90 patients (41.8 %). K-ras mutations were detected in 99 of the patients (46 %). K-ras was found to be wild type in 116 patients (54 %). Significant differences were detected between the K-ras wild-type and mutant groups with respect to age and the initial serum CEA levels. Patients with K-ras mutations were younger (p = 0.04) and had higher initial CEA levels (p = 0.02) compared to patients with K-ras wild type. The median overall survival (OS) time and 3-year OS rate for patients with a high initial CEA level (>5 ng/mL) were significantly shorter than those of patients with a low initial CEA level (<5 ng/mL) (50.5 months and 61.8 % vs. 78.6 months and 79.1 %, p = 0.014). Furthermore, the patients with low initial CA 19-9 levels (<37 ng/mL) had a significant better median OS interval and 3-year OS rate (76.1 months and 80.1 %) compared to patients with high initial CA 19-9 levels (>37 ng/mL) (37.6 months and 55.7 %, p = 0.04). Multivariate analysis indicated that stage at the time of diagnosis (p < 0.001) and low initial serum CEA level (p = 0.037) were independent prognostic factors of OS. For K-ras mutant patients, the stage at diagnosis (p = 0.017), low initial serum CEA level (p = 0.001), and low initial serum CA 19-9 level were found to be independent prognostic indicators of OS. Our findings demonstrate for the first time that the presence of a K-ras mutation correlated with high initial CEA and CA 19-9 levels in patients with metastatic colorectal cancer. Patients with high initial CEA and CA 19-9 levels may potentially predict the presence of a K-ras mutation, and this prediction may guide targeted therapies in these patients.

Male breast cancer: 37-year data study at a single experience center in Turkey.

PURPOSE: The aim of this study is to evaluate the effects of prognostic factors on the overall survival (OS) and locoregional control (LC) among male breast cancer (MBC) patients treated at Cerrahpasa Medical School Hospital, along with a review of the related literature. METHODS: The data of 86 patients treated for MBC from 1973 to 2010 are retrospectively reviewed. Patient demographics and clinical information, including the date of diagnosis, treatment, clinical course, and the date and causes of death are routinely recorded. RESULTS: Median follow-up was 66 months. Isolated local-regional recurrence and distant metastases were observed in 15 (17.4%) and 24 (34.1%) of the cases, respectively. The 5-year OS rate was 65.8%; the disease-free survival rate was 72.4%, and the LC rate was 89.7%. The prognostic factors influencing local relapse were the T stage (p=0.002) and the chest wall muscular invasion (p=0.027) in the univariate analysis. The prognostic factors influencing OS were the presence of a positive axillary lymph node (p=0.001) and the T stage (p=0.001) in the univariate analysis. The T stage (p=0.008) and node (N) stage (p=0.038) were significant prognostic factors for OS in the multivariate analyses. Also, the T stage (p=0.034) was found to be significant for LC. CONCLUSION: We found that only the tumor size and lymph node status were independent prognostic factors for survival. In addition, only the tumor size was an independent prognostic factor for locoregional relapse. Modified radical mastectomy and conservative surgical procedures had similar outcomes for LC.

Clinicopathological features and outcomes of patients with gastric cancer: a single-center experience.

AIM: To evaluate the location, histopathology, stages, and treatment of gastric cancer and to conduct survival analysis on prognostic factors. METHODS: Patients diagnosed with of stomach cancer in our clinic between 2000 and 2011, with follow-up or a treatment decision, were evaluated retrospectively. They were followed up by no treatment, adjuvant therapy, or metastatic therapy. We excluded from the study any patients whose laboratory records lacked the operating parameters. The type of surgery in patients diagnosed with gastric cancer was total gastrectomy, subtotal gastrectomy or palliative surgery. Patients with indications for adjuvant treatment were treated with adjuvant and/or radio-chemotherapy. Prognostic evaluation was made based on the parameters of the patient, tumor and treatment. RESULTS: In this study, outpatient clinic records of patients with gastric cancer diagnosis were analyzed retrospectively. A total of 796 patients were evaluated (552 male, 244 female). The median age was 58 years (22-90 years). The median follow-up period was 12 mo (1-276 mo), and median survival time was 12 mo (11.5-12.4 mo). Increased T stage and N stage resulted in a decrease in survival. Other prognostic factors related to the disease were positive surgical margins, lymphovascular invasion, perineural invasion, cardio-esophageal settlement, and the levels of tumor markers in metastatic disease. No prognostic significance of the patient's age, sex or tumor histopathology was detected. CONCLUSION: The prognostic factors identified in all groups and the proposed treatments according to stage should be applied, and innovations in the new targeted therapies should be followed.

Clinicopathological features and localization of gastric cancers and their effects on survival in Turkey.

BACKGROUND: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. MATERIALS AND METHODS: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. RESULTS: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. CONCLUSIONS: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

Male breast cancers behave differently in elderly patients.

OBJECTIVE: The aim of this study was to evaluate tumor characteristics, management and survival in elderly male breast cancer patients in comparison with younger men. METHODS: We reviewed medical records of 99 male breast cancer patients between 1972 and 2011. The median age of the patients was 64.5 years. Patient characteristics including clinicopathologic factors, treatment modalities, survival and prognostic factors were evaluated. Patients were subdivided into two groups according to their age (young, <65 years; old, ≥ 65 years) and compared based on these factors. RESULTS: Elderly male breast cancer patients had larger tumors in more advanced stages at the time of diagnosis compared with younger patients. In spite of the larger tumors at presentation, older patients had tumors with more favorable biological characteristics, such as higher ratio of estrogen and progesterone receptor expression. Ten-year cancer-specific survival for older patients was 49.2% compared with 55.8% in younger men (P = 0.8). Prognostic factors influencing overall survival in univariate analysis were: the presence of metastatic axillary lymph nodes (P = 0.0001), T stage (P = 0.001) and age ≥ 65 years. Multivariate analysis indicated T stage (P = 0.008) and N stage (P = 0.038) as the significant negative prognostic factors for overall survival. Although surgery, radiotherapy and hormone therapy were equally utilized in old and young patients, old patients were less likely to receive adjuvant chemotherapy. CONCLUSIONS: Our study demonstrated the differences in the clinical and biological characteristics of male breast cancer according to the age of the patients.

Gastric cancer: a case study in Turkey.

OBJECTIVE: The aim of this study was to determine age-specific incidence ratios, gastric cancer localization trend, histologic subtype and cancer related survival that whether have changed during the period from 1999 to 2010. MATERIALS AND METHODS: A total of 866 gastric cancer patients treated at the hospital were retrospectively evaluated. Categorical and continuous variables were summarized using descriptive statistics and were compared using the Chi-square and Mann-Whitney U-tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. RESULTS: The median age at diagnosis was 58 years. Trends concerning the median ages of the patients were increased (from 57 years to 59 years). The proportion of diffuse histological subtype gastric adenocarcinoma increased during the period from 1999 to 2010, and it was 27% between 1999 and 2002 and 32% between 2007 and 2010 (P = 0.04). The proportion of gastric adenocarcinoma localized in cardia increased during the period from 1999 to 2010, and was 7.2% between 1999 and 2002; and 22.5% in 2007 and 2010 (P = 0.004). For stage I that was diagnosed between 1999 and 2002, the relative survival was 67% and in patients diagnosed between 2007 and 2010 the rate was 85%. For stage II that was diagnosed between 1999 and 2002, the relative survival was 35% and in patients diagnosed between 2007 and 2010, the rate was 65%. Cox regression analysis was conducted based on age subgroup, diagnosis time, and gastric localization (proximal/distal) and for adenocarcinoma subtypes. Hazard ratio was 31.6 for stage IV (confidence interval [CI] = 10-42), 1.3 for cardia localization (CI = 1.04-1.6) and 1.37 for patients who had been diagnosed between 1999 and 2002 (1.14-1.78). CONCLUSIONS: The ratio of median age at diagnosis and proximal gastric adenocarcinoma, diffuse histologic subtype increased between 1999 and 2010. Cancer related survival significantly improved for stage I and stage II. Cardia localization and time of diagnosis between 1999 and 2002 had significantly poor outcome on relative survival.

Metachronous rectum metastases from gastric adenocarcinoma: a case report.

Introduction. Hepatic metastases of gastric adenocarcinomas are frequently observed due to the drainage into portal vein. Intestinal metastases disseminate from gastrocolic and mesenteric ligaments but they are seen very rarely and in most cases detected in postmortem studies. Case Report. A 74-year-old female patient with no known history of disease. Her complaints on application were epigastric pain, burning, and constipation. Gastroscopy showed a submucosal mass in the greater curvature of fundus and in colonoscopy, a mass with polypoid appearance that narrows the lumen at the rectum was detected. No far metastases or pathology were detected. Pathology report from gastric biopsy material demonstrated well-differentiated adenocarcinoma. Cytokeratin 7 (CK7) was found to be extensively strongly positive, Cytokeratin 20 (CK20) was negative in the immunohistochemical staining of the biopsy obtained from rectosigmoid area. Conclusion. Gastric cancer is among the frequent cancers today, most of which are adenocarcinomas. Although most of the metastases are observed in the liver, lungs, lymph nodes, and peritoneum, it should be remembered that intestinal metastases may be seen without the presence of any other metastatic focus. Our case is the first in literature reporting a rectum metastasis without any other organ metastasis.

A comparison of patient characteristics, prognosis, treatment modalities, and survival according to age group in gastric cancer patients.

BACKGROUND: The aim of this study was to investigate age-specific incidence rates and to compare disease stage, treatment, and survival according to age group in patients with gastric adenocarcinoma. METHODS: Gastric cancer patients treated at our hospital between 1999 and 2010 were retrospectively evaluated. We divided the cases into two subgroups: group 1 consisted of patients older than 70 years at the time of treatment, and group 2 included patients aged 70 years or younger. In all, 151 patients over 70 years of age and 715 patients age 70 years or younger were analyzed. Categorical and continuous variables were summarized using descriptive statistics and compared using statistical software. Overall survival rates were estimated via the Kaplan-Meier method. RESULTS: Median age at diagnosis was 58 years (range: 22 to 90 years). Between 1999 and 2002 the annual median age for patients aged older than70 years was 9.8%, which increased to 20% between 2007 and 2010. The one-year survival rate for patients with metastatic disease (stage IV) was 10.9% (95% CI: 8.9% to 12.9%) and 27.8% (95% CI: 17.3% to 38.2%) in groups 1 and 2, respectively (P = 0.015). The five-year survival rate for patients with non-metastatic disease (in whom curative surgery was performed) was 15.5% (95% CI = 12% to 19%) and 26.9% (95% CI = 25.9% to 27.9%) in groups 1 and 2, respectively (P = 0.03). There were no significant differences in gender, tumor localization in the stomach, tumor histology, perineural invasion (PNI), lymphovascular invasion (LVI), tumor stage, or type of surgery between the two groups. However, fewer of the patients in group 1 underwent adjuvant treatment (P = 0.02) and palliative chemotherapy (P = 0.007) than group 2 patients that were non-metastatic and metastatic at presentation, respectively. CONCLUSIONS: Groups 1 and 2 were similar in terms of histopathological features and surgical modality; however, the survival rate was lower in group 1 than in group 2. The incidence of gastric cancer was higher in the patients older than 70 years of age. Additional randomized studies are needed to further assess the safety and clinical benefit of chemotherapy in gastric cancer patients older than70 years of age.

Perineural invasion independent prognostic factors in patients with gastric cancer undergoing curative resection.

OBJECTIVE: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. METHODS: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. RESULTS: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. CONCLUSIONS: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors.

Paraneoplastic pemphigus associated with fludarabine use.

Paraneoplastic pemphigus is a severe mucocutaneous disease associated with B-cell lymphoproliferative disorders. A 51-yr-old man presented to the oncology clinic with mucocutaneous skin lesions after six cycles of fludarabine for non-Hodgkin's lymphoma. A punch biopsy from the skin showed suprabasal acantholysis and blister formation in the epidermis and upper dermis. Direct immunofluorescence demonstrated intercellular IgG deposition in all epidermal layers and complement (C3) at the basement membrane. The indirect immunofluorescence on rat bladder showed intercellular binding of IgG. These findings were consistent with paraneoplastic pemphigus associated with fludarabine use. The temporal association between fludarabine use and paraneoplastic pemphigus suggests there is an etiopathological link between these two entities.

Toxicity and survival results of a phase II study investigating the role of postoperative chemo-radioimmunotherapy for gastric adenocarcinoma.

BACKGROUND AND PURPOSE: To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. PATIENTS AND METHODS: 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). RESULTS: Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. CONCLUSION: Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Primitive neuroectodermal tumor of the pancreas. A case report of an extremely rare tumor.

Primitive neuroectodermal tumor (PNET) of the pancreas is extremely rare. Although the diagnosis of PNET is suggested by the light microscopic appearance of the tumor, it should be confirmed by the immunohistochemical evaluation of the c-myc expression and if possible, further determination of the particular chromosome translocation, t(11;22)(q24,q12). In this report, we present a male patient with pancreatic PPNET who had been followed up for 50 months. The related literature is also reviewed. In our case, the pathologic diagnosis was based on the positive immunoreactivity for CD99 in many of the tumor cells. The complementary cytogenetic studies were not possible in the private setting of the patient's treatment. The patient was 31 years old when first operated. Within 4 months of the first operation he had local recurrence. In the third year of his follow-up he had been discovered to have pulmonary metastases and another metastatic tumor in his lung was diagnosed the year after. The metastatic foci were primarily treated by surgical resections. He had chemotherapy after each resection of pulmonary metastatic foci. After 50 months of the initial surgical intervention, he succumbed to widespread thoracic and bone metastases. Because of the extreme rarity of PPNET in the pancreas, and its rather protracted course, we think our case may further contribute to the ever expanding database for this particular entity.

Simultaneous presentation of hepatocellular carcinoma in identical twin brothers.

Family history and hepatitis B virus (HBV) infection have been identified as risk factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC) diagnosed at the same time in identical twin brothers. Serological analyses of the patients showed that both were chronically infected with HBV. Molecular analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene region. Both of the patients were unresponsive to chemotherapy and died within the same month with an interval of I wk. With a review of the current literature, we discuss the role of HBV infection and genetic factors on hepatic carcinogenesis.