Search

Zusammenfassung Hintergrund Bei einzelnen Patienten mit kolorektalen Karzinomen (CRC) zeigt sich ein schlechter klinischer Verlauf innerhalb desselben UICC-Stadiums (Union for International Cancer Control). Die Identifizierung von zusätzlichen Risikofaktoren ist daher notwendig, um eine optimale Therapieplanung zu erreichen. Fragestellung In welchen Situationen kann Tumor Budding die klinische Therapieentscheidung beeinflussen und wie sollte die standardisierte Auswertung erfolgen? Material und Methode Aktuelle Publikationen zum Thema Tumor Budding werden mit Fokus auf die praktische Anwendung und potenzielle Problemfälle in der Bestimmung des Tumor Buddings erläutert. Ergebnisse Tumor Budding ist ein signifikanter Risikofaktor für einen schlechteren Verlauf des CRC und kann bei pT1-Karzinomen sowie Stadium-II-Karzinomen die Behandlung beeinflussen. Die Auswertung wurde durch die International Tumor Budding Consensus Conference (ITBCC) 2016 standardisiert und ist in der Praxis anwendbar. Schwierigkeiten in der Anwendung können durch die Kenntnis von potenziellen Problemfällen vermieden werden.

Naomi Hayashi,1 Yasuyoshi Sato,1 Yu Fujiwara,1,2 Naoki Fukuda,1 Xiaofei Wang,1 Kenji Nakano,1 Testuya Urasaki,1 Akihiro Ohmoto,1 Makiko Ono,1 Junichi Tomomatsu,1 Yukiko Sato,3 Hiroki Mitani,4 Takashi Toshiyasu,5 Shunji Takahashi1 1Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York City, NY, USA; 3Pathology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 4Head and Neck Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; 5Radiation Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JapanCorrespondence: Yasuyoshi SatoThe Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, 135-8550, JapanTel +8135200111Fax +81335200141Email yasuyoshi.sato@jfcr.or.jpPurpose: There have been few reports on the evaluation of cancer cachexia based on skeletal muscle mass index (SMI) in patients with head and neck cancer.Patients and Methods: One hundred and ninety-two head and neck cancer patients were enrolled. In definitive and adjuvant chemoradiotherapy settings, clinical outcomes were compared between cachexia and non-cachexia patients.Results: Forty patients were diagnosed with cachexia (20.8%). In the definitive setting, overall survival (OS) was significantly shorter in the cachexia group (3-year OS: 50.0% vs 88.5%; p < 0.01), and multivariate analysis identified UICC stage IV, baseline albumin of < 4 and cachexia as poor prognostic factors. However, cachexia was not significant in the adjuvant setting.Conclusion: Cancer cachexia was negatively associated with prognosis in patients with HNC who received definitive chemoradiotherapy. Nutritional intervention during chemoradiotherapy may improve survival in these patients.Keywords: head and neck cancer, squamous cell carcinoma of head and neck, sarcopenia, cachexia, muscle, skeletal, chemoradiotherapy, prognosis

Non-small cell lung cancer (NSCLC) is the second most frequently diagnosed tumor worldwide. Despite the clinical progress which has been achieved by multimodal therapies, including radiochemotherapy, and immune checkpoint inhibitor blockade, the overall survival of patients with advanced-stage NSCLC remains poor, with less than 16 months. It is well established that many aggressive tumor entities, including NSCLC, overexpress the major stress-inducible heat shock protein 70 (Hsp70) in the cytosol, present it on the plasma membrane in a tumor-specific manner, and release Hsp70 into circulation. Although high Hsp70 levels are associated with tumor aggressiveness and therapy resistance, membrane-bound Hsp70 can serve as a tumor-specific antigen for Hsp70-primed natural killer (NK) cells, expressing the C-type lectin receptor CD94, which is part of the activator receptor complex CD94/NKG2C. Therefore, we investigated circulating Hsp70 levels and changes in the composition of peripheral blood lymphocyte subsets as potential biomarkers for the advanced Union for International Cancer Control (UICC) stages in NSCLC. As expected, circulating Hsp70 levels were significantly higher in NSCLC patients compared to the healthy controls, as well as in patients with advanced UICC stages compared to those in UICC stage I. Smoking status did not influence the circulating Hsp70 levels significantly. Concomitantly, the proportions of CD4+ T helper cells were lower compared to the healthy controls and stage I tumor patients, whereas that of CD8+ cytotoxic T cells was progressively higher. The prevalence of CD3−/CD56+, CD3−/NKp30, CD3−/NKp46+, and CD3−/NKG2D+ NK cells was higher in stage IV/IIIB of the disease than in stage IIIA but were not statistically different from that in healthy individuals. However, the proportion of NK cells expressing CD94 and the activation/exhaustion marker CD69 significantly increased in higher tumor stages compared with stage I and the healthy controls. We speculate that although elevated circulating Hsp70 levels might promote the prevalence of CD94+ NK cells in patients with advanced-stage NSCLC, the cytolytic activity of these NK cells also failed to control tumor growth due to insufficient support by pro-inflammatory cytokines from CD4+ T helper cells. This hypothesis is supported by a comparative multiplex cytokine analysis of the blood in lung cancer patients with a low proportion of CD4+ T cells, a high proportion of NK cells, and high Hsp70 levels versus patients with a high proportion of CD4+ T cells exhibiting lower IL-2, IL-4, IL-6, IFN-γ, granzyme B levels.

Background/aim We compared patients with advanced gastric cancer [Union for International Cancer Control (UICC) III] versus patients with stage UICC IV and peritoneal carcinomatosis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) versus patients with stage UICC IV treated without HIPEC to ascertain if CRS and HIPEC improve overall survival (OS). Patients and methods We retrospectively analysed thirty-seven advanced gastric cancer patients who had been treated at our department from 2012 to 2017. The endpoint was median OS. Results Eighteen (49%) patients with UICC stage III showed a median OS of 37.4 months. Eight (21%) patients in the HIPEC group reached a median OS of 33.8 months. Median OS in the UICC IV group (11 patients, 30%) treated with a palliative concept was 6.2 months and therefore significantly worse (p=0.004). Conclusion A systemic approach combined with CRS and HIPEC in selected stage IV gastric cancer patients improves the OS comparable to patients in UICC stage III.

Tumor invasion into blood and/or lymphatic vessels, perineural invasion, and histopathological grading are evaluated to assess the biological aggressiveness of oral squamous cell carcinoma (OSCC). We aim to assess the prognostic impact of a novel scoring system, based upon the aforementioned histological parameters. Retrospective chart review of 334 patients with treatment-naive squamous cell carcinoma of the oral cavity. Statistical analysis was performed using univariate and multivariate analysis. Histological grade G1 or G2 were assigned 0 points and G3 or G4 1 point. Invasion of the lymphatic vessels, blood vessels, or perineural space was given 1 point. Zero points were given, when invasion was not detectable. The final score was conducted through addition of each parameter. Therefore, our scoring system ranged between 0 and 4 points. T-classification (p

Lymph node dissection in colon cancer is without a doubt necessary, it is just the extent of that dissection that is still under debate. As the individual steps of an oncologic operation cannot be separated from each other, analysis of the significance of lymph node dissection alone is difficult. It has been proven that the T category is directly related to the number and central spread of lymph node metastases. Micrometastases and isolated tumor cells may be detected in lymph nodes by using special staining techniques; their presence may worsen prognosis significantly and approximate it to UICC stage III. The numbers of dissected lymph nodes and the ratio of involved versus dissected lymph nodes have been used as markers for quality of surgery and histopathological evaluation. JMS 2018: 21 (2):109-113

Currently, right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC) are typically seen as different tumor entities. It is unknown if this subdivision by primary tumor location has an influence on the survival of patients with colorectal pulmonary metastasectomy (PM). We retrospectively analyzed our prospective database of 233 patients operated on for colorectal lung metastases between 1999 and 2014. Differences in the patient characteristics and the primary tumor and metastatic tumor burden were analyzed using χ2-tests. The long-term survival after PM of the three groups was analyzed with the Kaplan-Meier method and log-rank tests. In total, PM was performed for 37 patients with RCC, 57 patients with LCC, and 139 patients with REC. Patients with LCC were significantly more likely to have UICC stage IV primary tumor (44.2% LCC vs. 37.5% RCC vs. 22.8% REC, p = 0.012) and significantly more likely to have a history of additional liver metastases (45.6% LCC vs. 32.4% RCC vs. 27.3% REC, p = 0.046). The 5-year survival rates after PM for patients with RCC, LCC, and REC were 47, 66, and 39%, respectively (p = 0.001). The median survival times of patients with RCC, LCC, and REC were 55 months (95% CI: 42.2–66.8), 108 months (95% CI: 52.7–163.3), and 44 months (95% CI: 50.4–63.6), respectively. This study demonstrated a prognostic impact of the primary tumor localization in patients undergoing PM for colorectal lung metastases. Nevertheless, long-term survival was achievable in all groups.

Purpose To compare laparoscopic non-CME colectomy with laparoscopic CME colectomy in two hospitals with similar experience in laparoscopic colorectal surgery. Methods Data was collected retrospectively from Päijät-Häme Central Hospital (PHCH, NCME group) and Central Finland Central Hospital (CFCH, CME group) records. Elective laparoscopic resections performed during 2007–2016 for UICC stage I–III adenocarcinoma were included to assess differences in short-term outcome and survival. Results There were 340 patients in the NCME group and 325 patients in the CME group. CME delivered longer specimens (p p p p = 0.528, NCME 93.2% vs CME 88.9%, p = 0.132, respectively). Thirty-day morbidity, mortality, and length of hospital stay were similar between the groups. Conversion to open surgery was associated with decreased survival. Discussion Complete mesocolic excision (CME) is reported to improve survival. Most previous studies have compared open CME with open non-CME (NCME) or open CME with laparoscopic CME. NCME populations have been historical or heterogeneous, potentially causing bias in the interpretation of results. Studies comparing laparoscopic CME with laparoscopic NCME are few and involve only small numbers of patients. In this study, diligently performed laparoscopic non-CME D2 resection delivered disease-free survival results comparable with laparoscopic CME but was not safer.

AIM Multidetector computed tomography (MDCT) is the main preoperative decision-making tool in colon cancer treatment, thus the validation of daily clinical practice is warranted. The only published study validating the accuracy of MDCT in a national cohort was performed more than a decade ago. With neoadjuvant chemotherapy for patients with preoperatively assessed locally advanced cancer and the emergence of other personalized treatments we aimed to validate the accuracy of MDCT in a national cohort. METHOD The study is based on the Danish Colorectal Cancer Group (DCCG) database and included all Danish patients diagnosed with primary colon adenocarcinoma between January 2015 and December 2018. The primary study outcome was the accuracy of MDCT in identifying patients with locally advanced disease. The secondary outcomes were the accuracy of predicting UICC Stage I based on predicting the tumour category (pT3-T4 versus pT1-T2) and lymph node metastasis. RESULTS A total 3465 patients were included in the analyses regarding locally advanced colon cancer. The sensitivity and specificity were 0.61 (0.58-0.64) and 0.85 (0.83-0.86), respectively, for CT to predict locally advanced disease. The sensitivity and specificity were 0.63 (0.59-0.66) and 0.80 (0.78-0.81), respectively, for predicting UICC Stage I in 4496 patients. Thirty six per cent of the patients assessed as having locally advanced disease and 58% assessed as Stage I were misclassified by MDCT. CONCLUSION The present standard in Denmark questions whether the implementation of personalized medicine such as neoadjuvant adjuvant chemotherapy and tailor-made resections based on MDCT is justified.

Background In esophageal carcinoma, the numbers of metastatic and total removed lymph nodes (LN) are well-established variables of long-term prognosis. The overall rate of retrieved LN depends on neoadjuvant treatment, the extent of surgical lymphadenectomy, and the modality of the pathological workup. The question in this study is whether technically extended histopathological preparation can increase the number of detected (metastatic) LN with an impact on nodal UICC staging. Patients and Methods A cohort of 77 patients with esophageal adenocarcinoma was treated with Ivor Lewis esophagectomy including standardized two-field lymphadenectomy. The specimens were grossed, and all manually detectable LN were retrieved. The remaining tissue was completely embedded by the advanced “acetone compression” retrieval technique. The primary outcome parameter was the total number of detected lymph nodes before and after acetone workup. Results A mean number of 23,1 LN was diagnosed after standard manual LN preparation. With complete embedding of the fatty tissue using acetone compression, the number increased to 40.5 lymph nodes (p p Conclusions Advanced lymph node retrieval by acetone compression allows a reliable statement on the real number of removed LN. Results demonstrate an impact on the nodal UICC stage. A future multicenter study will examine the prognostic impact of improved lymph node retrieval on long-term oncologic outcome.

The function of Forkhead box O 1 (FOXO1) and pSerine256-FOXO1 immunostaining in esophageal cancer is unclear. To clarify the prognostic role of nuclear FOXO1 and cytoplasmic pSerine256-FOXO1 immunostaining, a tissue microarray containing more than 600 esophageal cancers was analyzed. In non-neoplastic esophageal mucosae, FOXO1 expression was detectable in low and pSerine256-FOXO1 expression in high intensities. Increased FOXO1 and decreased pSerine256-FOXO1 expression were linked to advanced tumor stage and high UICC stage in esophageal adenocarcinomas (EACs) (tumor stage: p = 0.0209 and p

Local failure is a major cause for low overall survival rates in advanced non small cell lung cancer (NSCLC). Among others, radioresistant tumor clones as well as geographical miss can explain these high local failure rates. One reason for geographical miss is a change of tumor related atelectasis in the course of radiotherapy. We present the case of a patient with UICC Stage IIIb NSCLC who presented with a large tumor related atelectasis. During definitive radiochemotherapy, the atelectasis resolved, which resulted in a massive tumor shift out of the planning target volume within 2 days. Without close monitoring by cone beam CTs and prompt replanning, this would have led to a geographical miss and relevant underdosage of the tumor. Furthermore, changes in anatomy and pulmonary function during treatment had implications for organs at risk and opened windows for dose escalation. We suggest at least biweekly CBCTs in patients with poststenotic atelectasis to ensure the rapid detection of geographical changes of the target and subsequent intervention if necessary.

Objective To analyze the survival rate of a nonselected pyriform sinus cancer population. Study Design Case series with chart review. Setting University hospital. Subjects and Methods A total of 122 patients were included in this study covering the 2002-2008 period. All patients had squamous cell carcinoma originating from the pyriform sinus. Survival and prognostic factors were analyzed. Results The 3- and 5-year overall survival rates were 39.7% and 2.4%, respectively. The 3- and 5-year survival rates without recurrence were 34% and 27%, respectively. The median survival rates by UICC stage were as follows: stage 1 and 2 patients, 60 months; stage 3, 40 months; stage 4, 19 months. Stage 4 patients had a lower median survival rate than other stages ( P = .039). The 5-year survival rate was 46% for patients having T3-T4 operable cancers treated by surgery vs 45% for patients treated by laryngeal conservation protocol (not significant). The 5-year survival rate for patients having nonoperable T4 cancers was 17.2%. The 3- and 5-year overall survival rates of N0 patients was significantly higher than N1 patients ( P = .042). N2 and N3 patients had 100% 5-year mortality. Conclusion This study showed that overall survival and therapeutic management depend on the initial stage of pyriform sinus cancer, notably on the N status. In particular, nonoperable T4 pyriform sinus cancer and N2 and N3 patients had a very poor prognosis. A laryngeal conservation protocol seemed as effective as surgical management in terms of survival.

Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p

Background: The only curative treatment option for intrahepatic cholangiocarcinoma (iCCA) is liver resection. Due to central tumor localization and vascular invasion, complex liver resections play an important role in curative treatment. However, the long-term outcomes after complex liver resection are not known. Methods: A retrospective cohort study was conducted for all patients undergoing liver surgery for iCCA. Complex liver resections included ante situm resections, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and major liver resection with vascular reconstructions. Results: Forty-nine patients (34%) received complex liver resection, 66 patients (46%) received conventional liver resection and 28 patients (20%) were not resectable during exploration. Preoperative characteristics were not different between the groups, except for Union for International Cancer Control (UICC) stages. The postoperative course for complex liver resections was associated with more complications and perioperative mortality. However, long-term survival was not different between complex and conventional resections. Independent risk factors for survival were R0 resections and UICC stage. Four patients underwent ante situm resection without any mortality. Conclusions: Complex liver resections are justified in selected patients and survival is comparable with conventional liver resections. Survival in iCCA is affected by UICC stage or resections margins and not by the complexity of the case.

BACKGROUND Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted. METHODS In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection. RESULTS Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P

Anastomotic leakage is the most serious surgical complication following colorectal resection, and surgical intervention is often required. The purpose of the study was to investigate short- and long-term outcomes after reoperation for anastomotic leakage. Patients with a symptomatic anastomotic leakage following a laparoscopic colorectal cancer resection from January 2009 to December 2014 were identified from our local prospective database. Patients were grouped according to the management of anastomotic leaks: local, lap, or open approach. Primary outcomes were length of stay, chance of bowel continuity, and overall mortality. A total of 113 patients were included. The median follow-up time was 40 months (0–82 months). Overall mortality was significantly associated with UICC stage III–VI disease (vs. UICC stage I–II disease) [adj. HR 5.35 (CI 2.32–12.4), p = 0.0001] and minimal invasive reoperation compared with open approach [local: adj. HR 0.12 (CI 0.03–0.52), p = 0.004; lap: adj. HR 0.32 (CI 0.12–0.86), p = 0.024]. Chance of bowel continuity was significantly increased in younger patients below 67 years [adj. OR 6.15 (1.76–21.5), p = 0.004] and following a local procedure [adj. OR 7.45 (1.07–51.8), p = 0.043]. Patients in the open group had significantly longer length of stay and time to initiation of adjuvant chemotherapy compared with those in the lap group. Our data confirms that minimal invasive reoperation for anastomotic leakage is a safe and feasible approach associated with short- and long-term advantages and can be chosen in selected cases.

Background/aim This study aimed to clarify the potential of modified Glasgow Prognostic Score (mGPS) as a prognostic biomarker and reveal the significance of fish oil (FO)-enriched nutrition in colorectal cancer (CRC). Patients and methods A total of 738 CRC patients from three different patient cohorts, including 670 patients in the biomarker study and 68 patients in the nutrition-intervention study, were analyzed. Results High preoperative mGPS was significantly correlated with well-recognized disease progression factors and advanced UICC stage classification. In addition, high mGPS was an independent prognostic factor in both cohorts, especially in stage III and IV patients. These statuses were maintained in postoperative course and correlated with sarcopenia. Furthermore, FO-enriched nutrition suppressed systemic inflammatory reaction and improved skeletal muscle mass and prognosis, especially in CRC patients with mGPS 1 or 2. Conclusion Assessment of mGPS could identify patients with high-risk CRC, who might be candidates for FO-enriched nutrition.

Objective: To detect the expression of CD133, E-cadherin and WWOX in colorectal cancer, analyze the correlations and pathological significance of the biomarkers. Methods: Two hundred and ten patients with colorectal cancer treated surgically between January 2007 and December 2015 were analyzed retrospectively. All patients had pathologic specimens and integrated clinical data. Pathologic specimens were retrieved for immunohistochemical examination of the expressions of CD133, WWOX and E-cadherin. The clinical data of these patients including gender, age, tumor location, tumor size, tumor differentiation, invasion depth, hepatic metastases, lymphatic metastasis, UICC stage and recurrence of tumor were retrieved to investigate their demographics and clinical characteristics. Results: In 210 specimens of colorectal cancer, the positive expression rate of CD133, E-cadherin and WWOX was 61.9%, 40.5% and 41.9%, respectively. The expression of CD133, E-cadherin and WWOX was significantly correlated with lymphatic metastasis, hepatic metastases and UICC stage (p

Summary The programmed death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are co-stimulatory molecules that contribute to the negative regulation of T lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumour-infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyse PD-L1 and PD-L2 expression and dendritic cells infiltration in tumour tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a and CD83 in 61 CSCC tissues. The immunofluoresence double-labelling technique was performed to detect the co-expression of PD-L1 or PD-L2 and CD1a or CD83 in tumour tissues. We found that 25 of 61 cases CSCC (40·98%) exhibited positivity for PD-L1, whereas 37 of 61 cases CSCC (60·66%) exhibited positivity for PD-L2. A higher percentage of CD1a-positive cases were observed on both PD-L1-positive and PD-L2-positive specimens compared with that of CD83-positive cases (92·29% versus 37·60%, 83·20% versus 33·16%). The expression of PD-L1 and PD-L2 on CD1a+ cells was significantly higher than that on CD83+ cells in tumour tissues of CSCC patients. Furthermore, the expression rate of PD-L1 was associated with UICC stage, and the expression rate of PD-L2 was associated with predominant differentiation and tumour size in CSCC. Our results indicated that higher expression of PD-L1 and PD-L2 on CD1a+ cells than that on CD83+ cells in CSCC tumour tissues may contribute to negative regulation in anti-tumour immune responses.

628 Background: The benefit of adjuvant chemotherapy in UICC stage III colon carcinoma has been demonstrated in numerous studies. For UICC stage II such an advantage was not shown. However, it remains controversial whether adjuvant chemotherapy might be considered in certain high-risk UICC stage II situations. High-risk factors include T4 tumors, associated with an increased risk of recurrence and poorer prognosis due to their more aggressive biological behavior. Methods: The present population-based, multicenter cohort study investigated the influence of adjuvant chemotherapy on survival and recurrence rates in UICC stage II in the high-risk situation T4N0M0. It is based on an anonymized nationwide ADT dataset and includes 208,030 patients diagnosed with colorectal cancer from 2002 to 2011. A total of 3544 patients with a T4 tumor were identified, of whom 34.3% (1215 patients) received adjuvant chemotherapy and 65.7% (2329 patients) none. Results: Median overall survival was markedly prolonged in subjects who received adjuvant chemotherapy from 4.5 years (SD 0.163, 95% CI 4.1-4.8) to 8.1 years (SD 0.474, 95% CI 7.2 -9.0; p < .001). After 5 years, 69.5% of chemotherapy patients were still alive compared to 45.1% of non-chemotherapy patients. After adjusting for factors in a multivariable Cox regression analysis, the significant benefit of adjuvant chemotherapy for overall survival was maintained (HR = 0.642, 95% CI 0.555-0.743, p < .001). The relative cumulative risk of recurrence in the multivariable analysis was HR = 0.696 (95% CI 0.580-0.843, p < .001) for chemotherapy patients. Furthermore, a highly significant improvement in relapse-free survival through chemotherapy was demonstrated (HR = 0.634, 95% CI 0.555-0.725, p < .001). Conclusions: In this representative study, a significant advantage of adjuvant chemotherapy for UICC stage II colon carcinoma patients with a T4 tumor was demonstrated in terms of overall survival, recurrence rate and relapse-free survival. On the basis of these results, adjuvant chemotherapy is recommended for the high-risk situation T4.

Aim Elevated levels of von Willebrand factor (VWF) are often observed in many diseases including colorectal cancer, but this finding is not definite. The aim of our study was to examine the change in VWF multimer distribution in patients with colorectal cancer. Method We randomly selected nine patients from each of the four Union for International Cancer Control (UICC) stages of colon cancer. VWF antigen (VWF:Ag), VWF-cleaving protease ADAMTS-13 level and factor VIII activity (FVIII:C) were determined. The multimer distribution of VWF was visualized using electrophoretic multimer analysis. Results The VWF multimer structure was normal with no difference between the four UICC stages. There was no significant increase in VWF:Ag and FVIII:C levels in the more advanced UICC stages. There was no significant difference in the ADAMTS-13 level according to the UICC stage. Conclusion There was no change in the VWF multimer distribution to indicate acquired von Willebrand disease.

The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status.

Objective: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). Patients: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. Results: Gender (P=0.0086), UICC stage (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I–II):UICC (III–IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19-9 (

BACKGROUND: Gastric carcinoma is often diagnosed at UICC stage 3 b or 4. R0 resection can be achieved only in very few such cases. Even for these patients the 5-year survival rate is less than 5 %. Surgical palliation is traditionally reserved for the treatment of severe tumour complications not responding to other forms of treatment. PATIENTS AND METHODS: We report on 21 patients who underwent palliative resection for gastric carcinoma at our institution between 2004 and 2007. Ten of these were assigned to palliative surgical treatment pre-operatively while this choice was made for 11 patients on the grounds of the intra-operative findings. We performed 17 gastrectomies, 3 proximal gastric resections and one distal gastric resection. RESULTS: It has been shown that the patients have an improved overall survival time as compared to patients who received non-surgical treatment. The perioperative risk was reasonable when pa-tients were carefully selected. Median survi-val for resected patients was 16 months. 80 % of pa-tients were alive after 6 months and approxi-mate-ly 60 % of patients were alive after 12 months. The peri-operative mortality was 0 % with a mean hospi-tal stay of 12 days. All patients were discharged home with proper bowel passage and analgesia as individually required. CONCLUSIONS: We are convinced that palliative gastric resection provides a pronounced survival benefit over any other palliative treatment options. Patients also have an improved quality of life.

Purpose Neoadjuvant therapy may reduce local rectal cancer recurrence after total mesorectum extirpation. This study was performed to assess whether multi-detector row CT (MDCT) is capable of reliably differentiating UICC I (surgery) from UICC II-IV (neoadjuvant therapy). Materials and methods 29 patients underwent preoperative MDCT of the abdomen in a portal venous phase. Two blinded readers independently evaluated the datasets on a dedicated workstation using axial and coronal reformations. Local tumor extension (T), nodal status (N) and distant metastases (M) were evaluated and the UICC stage was determined. Findings were correlated with postoperative histology. Results Histologically, 9 patients were UICC I; 20 UICC > I (II: 7; III: 11; IV: 2). Reader 1 correctly identified 3 / 9 as UICC I, overstaged 6 / 9, and correctly staged 20 / 20 as UICC > I. Reader 2 correctly identified 4 / 9 as UICC I, overstaged 5 / 9, understaged 4 / 20 and correctly staged 16 / 20 as UICC > I (PPV UICC I 100 % [50 %] reader 1 [reader 2], NPV 77 % [76 %], accuracy 79 % [69 %]). Reasons for overstaging by reader 1 (reader 2) included false-positive lymph nodes (LN) in 5 (5), overgrading T 1 tumors as T 3 in 1(0), and T overgrading in 4 / 5 (2 / 5) patients with false-positive LN. Conclusion MDCT failed to reliably identify UICC I in rectal cancer patients. Therefore, a strategy based solely on MDCT to identify patients who would benefit from neoadjuvant therapy does not seem appropriate.

Objective Anaplastic thyroid carcinoma arises from differentiated carcinoma and has a very aggressive character. In this study, we investigated the prognosis of patients with anaplastic carcinoma based on UICC stage. Patients and Methods We investigated the prognosis of 75 patients who were diagnosed as having anaplastic carcinoma at Kuma Hospital between 1983 and 2006. Of these patients, 14, 49 and 12 were classified into Stages IVA, IVB, and IVC respectively. Results Stage IVA patients showed a significantly better prognosis than Stage IVB or IVC patients ( p = 0.0017). All patients with Stage IVC died of carcinoma within 1 year regardless of whether locally complete resection was performed. Prognosis of Stage IVB patients who underwent curative surgery did not differ from that of Stage IVA patients, but the prognosis of those who did not undergo surgery or only received palliative surgery was as poor as that of Stage IVC patients. Conclusions Extensive surgical treatment is recommended for Stage IVA patients and palliative care is appropriate for Stage IVC patients. For Stage IVB patients, surgical treatment as a primary therapy is appropriate only when curative resection of the tumour is expected.

In a prospective multi-centre study data were collected on 1,999 patients (1273 men, 726 women; mean age 62.3 [19-99] years) with gastric carcinoma, admitted to one of 19 surgical departments in Germany between 1.4. 1986 to 30. 6. 1989. Previously treated patients as well as those with synchronous or metachronous tumours and carcinoma of the gastric stump had been excluded. The resection rate for gastric carcinoma was 82.7%, i.e. resection was no longer possible because of the advanced tumour stage in nearly 20%. The tumour was located in the upper third of the stomach in 30%, the antrum in 26.3%. An intestinal type of growth was present in 51.9%. An early carcinoma was diagnosed in 16.9% of operated patients; it had already metastasized to regional lymph nodes in 16.5%. Nearly 70% of patients with resectable tumours had metastases to the regional lymph-nodes, with distant metastases in 30%. An advanced tumour stage (UICC stage IIIB or IV) was present in 43%. Exclusively surgical treatment is not effective in these cases.

Aims:Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available for peripheral blood circulating tumor cell (CTC) evaluations in colorectal cancer(CRC) patients. Results are non-existent for the application of these techniques to the determination of progression and therapy response in Dukes stage D CRC patients.Patients and methods:Each month 30 ml peripheral blood of 30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA-M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed, as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC counting. Correlation between elevated CTC and macroscopic progression within 3 months was determined by Chi2test.Results:Microscopic CTC single cell, doublet, cluster number were found in correlation with CK20 QRT-PCR results (p< 0.01). There was a significant increase in microscopic CTC number, CK20 and decrease in TS QRT-PCR levels (p< 0.05) in the peripheral blood of the non-responder as compared to responder patients. Elevation of the CTC was in significant correlation with macroscopic progression of the disease in 3 months (p< 0.01).Conclusions:CTC number reflects the chemotherapeutic sensitivity of CRC patients. Elevation of circulating tumor cell number in peripheral blood is in correlation with macroscopic progression.

Radiochemotherapy (RChT) as adjuvant treatment for rectal cancer UICC stage II/III has been recommended by the National Cancer Institute (NCI) since 1991 and in Germany since 1994. Quality and results of postoperative treatment in day-to-day clinical practice in a complete region are evaluated retrospectively in a multi-institutional approach. 534 patients from six institutions treated between 1993 and 1998 were evaluated. The institutions covered a complete region with radiotherapeutic care. Patients were staged as follows: UICC I 1%, II 28%, III 69%, and IV 2%. 92% received RChT, 8% radiotherapy (RT) alone. Median follow-up of patients was 47 months (17–91 months). Only about 37% of expected patients were referred for postoperative treatment. The 5-year actuarial rate was as follows: local control 75% (63–84%), freedom from distant metastases 56% (44–63%), disease-free survival (DFS) 53% (42–59%), and overall survival (OS) 53% (45–64%). In multivariate analysis, local control was significantly influenced by T- and N-category, tumor grading, and RChT instead of RT alone. 6% (2–11%) of patients showed involved resection margins, in 33% of patients categorized pN0 less than the required twelve lymph nodes were examined, both leading to a significant decrease of local control. While the quality of adjuvant treatment followed consensus guidelines, the number of referred patients which was lower as expected and the inferior treatment results as compared to randomized studies indicate that the consensus recommendations for adjuvant treatment have not been fully accepted. Instead of patient referral according to UICC stage, patient selection by the surgeons has been performed according to individual risk factors. Efforts have to be made not only to improve treatment results in randomized studies but also to transfer and control these standards in daily practice.

The aim of this study was to evaluate the prognostic value of p53 nuclear accumulation and Bcl-2 expression after curative surgery for rectal cancer. Immunohistochemistry was performed using monoclonal antibodies (MAb) (DO-1 for p53; anti-human Bcl-2 MAb, clone 124, for Bcl-2) on formalin-fixed, paraffin-embedded tissues of 160 rectal carcinomas (UICC stages I-III), and results were compared with data from the prospective registry of rectal cancer by univariate and multivariate logistic regression model focusing specifically on recurrence. Survival was calculated by the Kaplan-Meier method and proportional hazards model. p53 nuclear accumulation was documented in 39% (n=63) of tumours and was associated with a higher incidence of tumour progression (local or distant recurrence) and poorer disease-free survival (P

100 consecutive newly diagnosed patients with nasopharyngeal carcinoma (NPC) since January 1994 were the subjects for studying various factors related to the delay in the confirmation of the diagnosis. 79 of them were males and the peak age of incidence was the 5th decade. 92% were Chinese, 7% Malay and 1% Indian. 76% were agriculture worker or labourers with 66% having either no formal education (16%) or only primary level education (50%). For 50% of patients neck swelling was the firstsymptom, 26% had nasal symptoms, 12% ear symptoms and 11% had symptoms due to intracranial extension of tumour. As many as 80% were at UICC Stage IV at the time of diagnosis. Wliile the median delay, on the part of patients, in consulting a doctor was 2.5 days, the median delay on the part of the doctors to confirm the diagnosis of NPC was as long as 127 days, which was particularly worse when the patients presented with ear symptoms (266 days) followed by those with neck swelling (94 days). For those patients who were required to undergo more than one nasopharyngoscopy and biopsy the median doctor's delay was 144 days. Since 82% of patients had consulted general practitioners who remained the first-line healtl1~service provider, it is suggested that their level of awareness with regards to NPC be significantly raised so that the delay on their part be greatly minimized.

Osseous metastases to the hand are very rare. Only a single case of osseous metastasis of hepatocellular carcinoma to the hand has been reported in the literature to date. We report a case of osteolytic metastasis of the right first metacarpal as first manifestation of unresectable, alpha-fetoprotein-negative hepatocellular carcinoma (pT3, Nx, M1, UICC stage IVB, Okuda's stage I). The therapy consisted of R0-resection and hormonal therapy with tamoxifen 2 x 10 mg/d orally. Generally patients with metastatic cancer to the bones of the hand have a very poor prognosis.

Long-term control of hilar cholangiocarcinoma (CCA) and extrahepatic cholangiocarcinoma (CCA) in general can only be obtained with complete surgical removal of all neoplastic tissue in toto either via surgical resection or transplantation [1]. Most investigators have demonstrated that complete surgical resection with negative margins (R0 resection) is the most important determinant of survival in hilar CCA [2, 3]. However, only a minority of patients are able to receive an oncologic resection [4]. Moreover, even after complete resection with negative margins the overall survival of patients with hilar CCA has been reported to range from 30 % to 52 % [5]. Murakami et al. [6] suggested that patients with UICC stage II and III CCAs to receive adjuvant therapy due to the high recurrence rate compare to Stage I tumors. The most common site of first recurrence after oncologic resection of hilar CCA is locoregional which often leads to potentially fatal complications such as biliary obstruction, sepsis and liver failure [4, 7, 8]. Only approximately 10–15 % of patients develop distant metastases before locoregional recurrence [7].

Background: The feasibility of the latest edition of the Japanese General Rules for Gastric Cancer Study (GRGCS) is evaluated by comparison with the TNM system. Methods: In a 5-year period from 1985 to 1989, 978 patients with gastric cancer underwent laparotomies at the Dept. of Gastroenterological Surgery, Aichi Cancer Centre, Japan. All the patients have now been followed up for 5 years or until death. These patients were retrospectively classified into appropriate clinical stages and residual tumour status on the basis of the GRGCS and the 4th edition of the TNM classification by the UICC, and survival curves for various stages and subgroups were evaluated. Results: The GRGCS classification provided useful information by splitting UICC stage IV into stages IVa and IVb, and R0 into curabilities A and B, both subgroups showing significant differences in the survival curves. Conclusions: The new edition of the GRGCS can be recommended as a useful staging manual for gastric cancer.