European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

Published by WB Saunders
Print ISSN: 0748-7983
BACKGROUND: To validate the clinical value of the One-Step Nucleic Acid Amplification (OSNA) Breast Cancer System for the intraoperative detection of sentinel lymph node (SLN) metastases in early-stage breast cancer patients in a Chinese population, a prospective, multicenter trial, the China Breast Cancer Clinical Study Group (CBCSG)-001c trial, was conducted. The present study focused on the prospective comparison of the performance between OSNA and touch imprint cytology (TIC). METHODS: The retrieved SLNs were divided into sections. Alternate slices from the tissue blocks were subjected either to OSNA analysis or to postoperative histopathology evaluation through serial sectioning. TIC was performed on every sample surface of each tissue block and was used by the surgeon to determine whether to perform an immediate ALND. RESULTS: A total of 552 patients qualified for the analysis. The sensitivity, specificity, and overall accuracy of OSNA were 87.8%, 89.6%, and 88.4%, respectively, on a per-patient basis compared with those of TIC, which were 81.3%, 96.9%, and 92.0%, respectively. OSNA detected more micrometastasis-involved nodes than TIC (52.8% vs. 25.0%; p = 0.029) on a per-node basis. Tissue allocation bias (TAB) was the main cause of discordant results. The performance of TIC varied significantly among the institutes, while the performance of OSNA was steady. CONCLUSIONS: Both OSNA and TIC can serve as qualified intraoperative assessments of SLNs. For institutes lacking the support of experienced cytopathologists, OSNA can be the first choice for the intraoperative assessment. In addition, OSNA can be applied as a complement to histopathology assessment. However, the results of the present study do not support the routine application of OSNA in the entire SLNs in place of pathology with serial sectioning.
While sentinel lymph node biopsy (SLNB) is established in the management of small unifocal breast cancer its role in management of multifocal (MF), multicentric (MC) and larger tumors is still evolving. Medline was searched; studies meeting pre-determined criteria were included. Data were extracted and entered into evidence tables. Twenty six studies met inclusion criteria and reported data on accuracy; no randomized trials were identified. For MF cancers (n = 314 cases), success rate for identification of an SLN was 86-94%, SLN positivity rate 42-59%, false negative rate (FNR) 0-33% and overall accuracy 78-100%. For MC (n = 294 cases): success rate 92-100%, SLN positivity rate 25-61%, FNR 4-8% and accuracy 96-100%. For 'multiple breast cancer' (studies combining MF/MC cases; n = 996 cases): success rate 92-100%, SLN positivity rate 12-63%, FNR 0-25%, and accuracy 82-100%. For larger tumors (n = 1912 cases): success rate 86-100%, SLN positivity rate 49-77%, FNR 3-18% and accuracy 85-98%. For MC/MF and larger cancers overall non-SLN positivity rates were up to 82%; axillary recurrence rates were low but seldom reported. There are no randomized trials evaluating the safety of SLNB in MF/MC and larger breast cancers. Based on limited evidence, success rate and FNR appear to be similar to those for small unifocal cancers, however node positivity rates are higher and rates of non-SLN positivity are very high. Awareness of these issues is essential when recommending SLNB based axillary management for these higher-risk tumors.
Clinically serosa-positive (T3-4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer. Patients with T3-4 gastric cancer received one course of S-1 (80mg/m(2) daily for 3 weeks) and cisplatin (60mg/m(2) on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities. Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2. This multi-modality treatment seems to be feasible and safe for T3-4 gastric cancer.
Complete tumour excision in breast conserving surgery (BCS) is critical for successful outcome; involved circumferential resection margins are associated with increased disease recurrence. However, the importance of an involved anterior margin (IAM) is less clear. The purpose of this study was to review an aggressive approach to IAM and hence assess whether anterior margin re-excision (RE) yields clinical benefit. A review of prospectively collected clinical and pathology data was performed for all patients who underwent BCS between 2006 and 2010 through a single cancer centre. An involved margin was defined as < 1 mm clearance of invasive or in-situ breast cancer. 1667 patients underwent BCS for invasive and/or in-situ disease, of whom 114 underwent RE. A total of 170 involved margins were identified: most commonly the anterior (52 margins) followed by the posterior (39 margins) and inferior (31 margins) margin. Patients with IAM were more likely to have grade 3 invasive disease (p = 0.0323) but less likely to have residual disease found at re-excision (2/49 vs. 32/101 margins, p = 0.0033); there were no differences when in-situ characteristics were compared. RE of IAM after BCS rarely yields further disease; multi-disciplinary teams should consider whether further therapy for an IAM is required on a patient by patient basis.
Radiofrequency ablation (RFA) is considered to be the most promising non-surgical ablation technique for the treatment of small breast cancer. However, few data are available regarding long-term follow-up of patients treated with this modality. Since 2005, we have performed RFA and sentinel lymph node (SLN) biopsy in 19 cases. Axillary lymph node dissection (ALND) was performed in patients with positive SLNs. From 24 to 202 days after RFA, the ablated tumour tissue was excised by mammotome biopsy and examined histologically or immunohistochemically with H&E staining, nicotinamide adenine dinucleotide (NADH)-diaphorase staining, and single-stranded (ss) DNA staining. All cases were followed-up after breast radiation and systemic therapies. Although complete response was histologically confirmed in only 8 cases, NADH-diaphorase and ssDNA staining did not demonstrate any viable tumour cells in the ablated lesions. At a mean follow-up of 60 months (follow-up range, 37-82 months), there were no cases of in-breast recurrence, although one patient died due to hepatic metastases. Cosmesis of the conserved breast was excellent or good in all of the cases, but a hard lump was persistent after RFA in half of the cases. The long-term outcome of patients treated with RFA is encouraging with regard to cosmesis and local control. Because a persisted lump may cause patient discomfort, anxiety and fear, however, further studies are needed to establish the optimal technique. Moreover, a prospective study will be required to determine the equivalency in local recurrence rates between the RFA therapy and conventional breast-conserving treatment.
Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression. To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer. One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥ 50% stroma were classified as stroma-high. Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07-5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08-8.32; 0.034). TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies.
The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm. Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death. TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.
In recent years, surgeons have utilized Harmonic instruments to perform breast cancer resection. Retrospective and prospective studies have demonstrated that the use of this surgical device for mastectomy and axillary dissection can reduce perioperative blood loss, seroma formation, and duration and total amount of drainage. No study has analyzed the feasibility of Harmonic instruments in breast-conserving surgery. We conducted a prospective, randomized clinical trial comparing Harmonic instrument and conventional surgery in the performance of breast-conserving surgery and axillary procedures to determine differences in surgical procedures, postoperative outcome, and complications. One hundred and six patients with operable breast cancer who underwent breast-conserving surgery at a single institution between December 2009 and January 2011 were included in the analysis. Surgery was performed in 52 patients with the Harmonic Focus(®) device and in 54 with scissors and electrocautery. This study focused on operative time, drainage volume, and postoperative outcome measures like blood loss, surgery related complications and patient-reported postoperative pain. We found a multivariable independent influence in axillary seroma formation and volume of breast drainage with HS. Evident difference in volume and duration of axillary and breast drainage, subjective and objective postoperative pain, reduction in serum hemoglobin, size and weight of resected breast tissue and length of hospital stay in favor of the Harmonic instrument could also be shown. The Harmonic instrument provides key benefits in surgical technique, postoperative outcome, and complication rates in breast cancer surgery.
Uveal melanoma is characterised by a high prevalence of liver metastases and a poor prognosis. To review the evolving surgical management of this challenging condition at a single institution over a 16-year period. Between January 1991 and June 2007, among 3873 patients with uveal melanoma, 798 patients had liver metastases. We undertook a detailed retrospective review of their clinical records and surgical procedures. The data was evaluated with both uni- and multivariate statistical analysis for predictive survival indicators. 255 patients underwent surgical resection. The median interval between ocular tumour diagnosis and liver surgery was 68 months (range 19-81). Liver surgery was either microscopically complete (R0; n = 76), microscopically incomplete (R1; n = 22) or macroscopically incomplete (R2; n = 157). The median overall postoperative survival was 14 months, but increased to 27 months when R0 resection was possible. With multivariate analysis, four variables were found to independently correlate with prolonged survival: an interval from primary tumour diagnosis to liver metastases >24 months, comprehensiveness of surgical resection (R0), number of metastases resected (< or = 4) and absence of miliary disease. Surgical resection, when possible, is able to almost double the survival and appears at present the optimal way of improving the prognosis in metastatic uveal melanoma. Advances in medical treatments will be required to further improve survival.
Pathological data on 1000 breast lesions obtained from Jordanian females were analyzed and compared to data available from other countries or ethnic groups. Ductal carcinoma was the most frequently encountered lesion followed by fibrocystic disease (mammary dysplasia), fibroadenoma and mastitis. The mean age of Jordanian females with ductal carcinoma was 44.5 years, and many patients presented with advanced stage of the disease as evidenced by the high frequency (74.6%) of nodal metastases in the patients who had axillary lymphadenectomy. The frequencies of medullary and mucinous (colloid) carcinoma were not greatly different from those in other countries, but lobular carcinoma had a substantially low rate of occurrence. Many patients with lactation-associated lesions such as mastitis, galactocele and lactating adenomas were noted, which is attributed to the high fertility rate in Jordan.
Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging. Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq) (99m)Tc-nanocolloid injected peritumorally, and 0.5-1.0 ml Patent Blue V injected intradermally. Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found. Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.
To evaluate the surgical management of patients who underwent VLNB for breast microcalcifications. This retrospective study compared the histological results and the surgical procedures in two groups of patients, group 1: large-core needle biopsy n=1009, and group 2: surgical biopsy n=270. After VLNB, 54% patients were not operated on after stereotactic large-core needle biopsy, 42% underwent one operation, 4% underwent two operations and 0.2% underwent three operations. No surgery was performed for 95% of benign lesions. Multiples operations were necessary in 12% of patients with malignant lesions of VLNB group compared to 45% in the surgical biopsy group. The rate of underdiagnosis of borderline lesions and ductal carcinomas in situ was 16% by the large-core biopsy technique. VLNB constitutes an alternative to surgical biopsy. This procedure avoids surgery for most benign lesions and reduces the number of surgical procedures in malignant lesions.
Melanoma is the most malignant type of all skin cancer types. It causes over 75% of all skin cancer related mortality. In the Netherlands, the total number of new diagnosed melanoma patients is expected to increase from 2400 patients in 2000 to 4800 patients in 2015. After surgical treatment, 20-28% of melanoma patients present with loco-regional recurrence, 26-60% with regional recurrences, and 15-50% with distant metastases. Early detection of lymph node (micro) metastases by means of a sentinel lymph node biopsy (SLNB) is therefore of crucial importance since early lymph node dissection decrease treatment morbidity and improve overall survival. However when patients present with palpable nodes, given the heterogeneity in survival, the suspicion rises that numerous patients have a form of subclinical dissemination, which can remain undetected by current modern imaging methods. Biomarkers could illuminate on this matter, although there is very little understanding of their biological significance. It can be expected that the strongest biological markers are surrogates of key biological events. The protein S-100B seems to be the best analyzed biomarker in melanoma. It has the potential to identify high-risk stage III melanoma patients who may benefit from adjuvant systematic treatment. In the stratification of new adjuvant therapeutic trials in patients with loco-regional recurrences, we therefore recommend the use of S-100B in the stratification. Since an effective (adjuvant) therapy for loco-regional metastatic and disseminated melanoma is recently introduced, the use of S-100B seems to alter dramatically in the near future.
High preoperative serum S-100B values and Standardized Uptake Values (SUV) of Fluorodeoxyglucose (FDG) in PET for clinically stage III melanoma patients could be indicators of recurrence after surgical treatment. Aim was to assess the correlation and the prognostic value of these markers. All melanoma patients with palpable nodal metastases, without distant metastases, were included from February 2004 to December 2007. Preoperative SUV and S-100B was determined. The correlation between SUV and S-100B and their relations with DFS and DSS were calculated by Cox Proportional Hazard Analysis. 62 Patients, median age 56.9 years, were included in the study. An elevated S-100B was found in 31 patients (50%) and elevated SUV in 24 patients (38.7%). No relation was found between S-100B and SUV. DFS was reduced (31.1%) for patients with an elevated S-100B (HR = 3.1; p = 0.02) in comparison to a normal S-100B (44.6%). The DFS was 42.0% for patients with a SUV below the cut-off point and 29.0% for patients with an elevated SUV (HR = 1.1; p = 0.8). DSS was 60.7% in a normal S-100B and 44.7% for patients with an elevated S-100B (HR = 2.2; p = 0.07). DSS was 59.1% for patients with a normal SUV and 43.5% for patients with elevated SUV (HR = 1.1; p = 0.8). S-100B and SUV in stage III melanoma are not correlated and each have different associations with various histopathological factors. S-100B, in contrast with SUV, is associated with nodal tumor load, and when elevated, predicts a shorter DFS. Preoperative serum S-100B and Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in clinically stage III melanoma are not correlated. S-100B is a strong predictor for Disease Free Survival (DFS) in stage III melanoma.
This study documents patient outcomes with one department's approach to performing partial hepatectomy. 101 consecutive patients underwent: preoperative dehydration; intraoperative CVP <5 cm H(2)O and selective continuous vascular occlusion. Outcome variables: pathology; type of hepatic resection; intraoperative blood loss and transfusion rate; 30 day morbidity and mortality; disease free and long term survival. Perioperative liver function was assessed by serial blood sampling. Of 101 resections: 90% malignant disease; 59% major resections and 35% synchronous procedures. Median estimated blood loss was 400 mL (mean 512 mL, range 50-3000 mL) with postoperative transfusions in 4%. Thirty day morbidity was 20% with no deaths. Median time to local recurrence after colorectal liver metastases resection was 17.1 months with 3 year survival of 51%. Distinct perioperative changes in hepatic function were seen. Selective continuous vascular occlusion and perioperative fluid restriction result in minimal blood loss, low morbidity and zero mortality in patients undergoing partial hepatectomy.
To analyse results with a standardized HILP procedure in terms of response rate, recurrence pattern and complication rate. From 1992 to 2003 HILP with melphalan and dactinomycin was performed in 101 patients with loco-regional metastases of malignant melanoma of the limbs. Among these were 66 women and 35 men with a median age of 62 years. Forty patients were in M. D. Anderson stage IIIA, 51 patients in stage IIIAB and 9 had stage IV disease at the time of perfusion. If not been done before, regional lymph node dissection preceded limb perfusion in the same setting. A complete response (CR) was observed in 58 out of 87 evaluable patients. Twenty-one patients achieved a partial response (PR) and eight patients were non-responders. The overall response rate was 90.8%. The median recurrence-free interval after CR was 21 months. Severe toxicity (Wieberdink IV/V) was observed in five patients necessitating fasciotomy in four of them and above knee amputation in one patient. All further cases presented with grade II-III toxicity. The overall survival was 42 months, with a 5-year survival rate of 38%. Survival significantly differed according to stage of disease. HILP is an effective treatment for loco-regional tumour relapse of malignant melanoma of the extremities and has improved by modification of technique. In the absence of regional lymph node and distant metastases long-term survival can be achieved in responders.
We evaluate the number of surgical two-stage procedures after FSA during breast-conserving therapy (clinical false negative result of FSA) and investigate the influence of microcalcifications, small tumour diameter, neoadjuvant therapy and preoperative biopsy on the clinical false negative rate of FSA. We retrospectively examined 1016 patients after intraoperative FSA during breast-conserving therapy for breast cancer operated between 1995 and 2001 at the Medical University Vienna. Only 9% of all patients had to undergo a two-stage operation due to a false negative intraoperative FSA result. The annual local recurrence rate was 1.2% in all patients with no difference between one- and two-stage operated patients. In situ and pT1 lesions were similarly distributed between one-stage and two-stage operated patients. The use of neoadjuvant therapy and stereotactic biopsy (reflecting non-palpable lesions and microcalcifications) were significantly predictive for a false negative FSA result. The use of a preoperative core biopsy, however, reduced the necessity of performing a two-stage operation. Our study demonstrates that FSA leads to a low rate of two-stage operations. Small lesions and microcalcifications as well as the occurrence of intraductal cancer cells and neoadjuvant therapy increased while preoperative core biopsy reduced the false negative rate of FSA. Overall local recurrence rates after FSA were acceptable.
The aim of this study is to identify prognostic factors influencing survival in patients with gastrointestinal stromal tumors (GISTs) and to identify a mathematical model that can predict lifetime expectation. One hundred and two patients with GISTs, were followed retrospectively for a median period of 32 months (from 1 to 82 months). Complete follow-up data were available in 72 cases. All tumors were surgically resected and examined by conventional light microscopy, immunohistochemistry and image analysis. The tumors' location, size, histologic characteristics, immunophenotype, proliferative activity index (assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 immunoreactivity) and the apoptotic markers bcl-2 and bax, were considered as potential prognostic factors and were correlated with patient survival. Tumor size >8 cm (p<0.03), presence of necrosis (p<0.02), number of mitoses >5/10 HPF (p<0.01), metastasis (p<0.001), and PCNA index >10% (p<0.004) were significant predictors of poor survival. Bcl-2 protein (p<0.0007) was a favorable prognostic indicator. If all tumors were treated as of uncertain malignant potential, the following mathematic model named GISTs Prognostic Index (GPI), could be formed by the linear regression technique: GPI exp=(49.6 months-Status of metastasis x 22.9185-Size in cm x 0.6801+bcl-2 expression% x 0.2569) (r(2)=0.67) (Prob>F=0.0001). Tumors' size, necrosis, mitoses, metastasis and PCNA index are independent poor prognosticators, while bcl-2 protein is associated with favorable prognosis. An interesting equation for survival in patient with GISTs has been reported.
To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. Mean age was 55+/-17 years. Mean tumor size was 15+/-6cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p=0.0005) and biopsy (p<0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT+/-IOERT in patients with high-grade tumors (p=0.005) and/or microscopically positive margins (p=0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p=0.036). Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection.
To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.
The management of desmoid tumours, previously based on strategies employed for sarcomas, should be reassessed, given the morbidity of interventions used in their treatment. Long-term follow-up (median 123 months) of a series of 106 treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome. Desmoids typically evolved actively over a median period of 3 years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17 months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy. Desmoids are relatively indolent tumours needing different approaches than sarcomas. Direct surgery is advisable only in primary lower trunk wall/girdle locations. Wait-and-see and medical treatment is preferable in other types of presentations.
RSU 1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol) and Mitomycin C (MMC) have both been shown to be directly cytotoxic to hypoxic cells. Repeat and transient dearterializations of a liver tumour would cause its cells to become intermittently hypoxic. In this experiment the therapeutic gain of RSU 1069 and MMC was evaluated when combined with either a single or repeat dearterializations of a transplanted liver tumour. The tumour growth during the first 6 days was significantly delayed when the administration of RSU 1069 (40 mg kg-1, i.p.) was followed 15 minutes later by a single dearterialization for 2 hours compared with sham operation (P = 0.0369) or either treatment alone (P = 0.0142 vs RSU 1069 alone and P = 0.0031 vs a single dearterialization for 2 hours alone). Furthermore, RSU 169 administered 15 min prior to a single dearterialization for 2 hours is more effective to retard tumour growth than MMC either alone (P = 0.0198) or with the same period of dearterialization (P = 0.0326). Repeat dearterializations (2 hours/day) during 5 days effectively retarded the growth of the tumour by itself (P = 0.015 vs sham operation). A larger growth delay was obtained when RSU 1069 was administered 15 min before the first dearterialization (P = 0.009 vs sham operation), though the growth delay between those two groups was not significant (P = 0.07). Survival time was significantly prolonged when repeat dearterializations were combined with RSU 1069 (P = 0.007 vs sham operation; P = 0.0009 vs RSU 1069 and P = 0.003 vs repeat dearterialization alone).(ABSTRACT TRUNCATED AT 250 WORDS)
We prospectively compared the ability of magnetic resonance imaging (MRI) to measure residual breast cancer in patients treated with different neoadjuvant chemotherapy regimen. Forty patients with locally advanced breast carcinoma underwent neoadjuvant chemotherapy. Twelve patients received 5-fluoro-uracyl-epirubicin-cyclophosphamide (FEC-group, six cycles), 28 (DXL-group) received docetaxel-based chemotherapy (six cycles DXL-epirubicin: 13 patients, eight cycles DXL alone: 15 patients). All patients had baseline and preoperative MRI. The spread of pathologic residual disease (PRd) was compared to preoperative MRI measures according to chemotherapy regimen. MRI over/underestimation of the spread of residual tumour was never superior to 15mm in FEC group, whereas it appeared in 11/28 (39%, 30-48%-95% CI) patients in DXL group (p=0.017). Tumour shrinkage led to single nodular residual lesions in FEC group, whereas vast numerous microscopic nests were observed in docetaxel group in pathology. Among tumours treated with a taxane-containing regimen, residual disease was frequently underestimated by MRI because of PRd features.
To determine overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer, outside of randomized trial, with a long term follow-up and to identify prognostic factors. A consecutive series of 108 patients treated for a first relapse of a FIGO stage III ovarian cancer was retrospectively included from December 1999 to November 2004. Each patient was treated with platinum-based chemotherapy in case of late (>6 months) relapse and with salvage chemotherapy without platinum in case of <6 months relapse. For statistical analysis the studied parameters were age, histological subtype, the completeness of initial surgery, disease-free period, localization of the relapse, clinical response to second-line chemotherapy, the completeness of secondary cytoreductive surgery (SCS) when it was performed. Median follow-up from the first relapse was 40 months. From the 108 patients, 35 underwent SCS. Median overall survival from the first relapse was 13 months in case of no SCS or non-optimal SCS and 35 months for patient with an optimal SCS (p = 0.006). In a multivariate analysis age, disease-free period, the clinical presentation of the relapse, completeness of SCS and response to second line chemotherapy appeared to be independent prognostic factors. Prognostic factors of ovarian cancer relapse are directly or indirectly linked with the feasibility of a complete SCS. Thus in the case of an ovarian cancer relapse, the feasibility of SCS must be considered in order to give the patient the best chance to experience its complete removal.
To evaluate the diagnostic and therapeutic procedures which were followed in a European Organization for Research and Treatment of Cancer (EORTC) randomized clinical trial investigating the role of radiotherapy in breast-conserving treatment (BCT) for ductal carcinoma in situ (DCIS) of the breast. The medical files of 824 of the 1010 randomized patients (82%) were reviewed during site visits to 30 participating institutes. Large variations occurred, particularly in the surgical procedures and histopathological work-up which were performed. Important risk factors like tumour size and margin status were poorly quantified in the medical files. These findings emphasize the need for establishing uniform guidelines for diagnostic and therapeutic procedures for DCIS, and for clearly defined risk factors for recurrence after BCT for DCIS. Because of its randomized nature, the main question of the trial, i.e. the effect of radiotherapy on the risk of local recurrence, will not be influenced by variation. The risk of local recurrence in itself, and hence the success of BCT for DCIS, may however be influenced by the quality of the initial procedures that were conducted.
The expression of the c-myc protein product (p62 c-myc) and deoxyribonucleic acid (DNA) ploidy status was determined by a flow cytometric technique in 83 patients with colorectal cancer followed up for a median of 30 months (range 6-60 months). The OM-11-906 antibody, used to detect p62 c-myc, revealed a 62 kDa and 45 kDa band on Western blots in tumours. Correlation of quantitative dot blotting of tumour mRNA to flow cytometric p62 c-myc expression was good (r = 0.87, P less than 0.01). Levels of p62 c-myc varied in colorectal cancer and low levels (less than 20 fluorescein units) correlated with improved survival (log rank chi 2 = 4.69, df = 1, P = 0.03), and this was a better prognostic index than DNA ploidy (log rank analysis chi 2 = 2.38, df = 1, P less than 0.1). Although expression of the c-myc gene was found, using the OM-11-906 antibody, to be a prognostic feature in colorectal cancer, these and other results need to be interpreted with caution given the presence of two protein bands by Western blotting.
Chondroblastoma is an infrequent and unique neoplasm that is histologically characterized by chondroblastoma cells, osteoclast-like giant cells and sometimes reactive osteoid. Although it is generally regarded as benign, it may recur and sporadically metastasize to the lung. Many important questions concerning the prognostic factors and adequate surgical treatment of chondroblastoma have not been fully answered and remain controversial. The purpose of this study was to determine clinicopathological features useful in prediction of the tumour behaviours. Eleven chondroblastoma cases were reviwed clinicopathologically. According to Enneking's radiographic grading system, seven cases were classified as stage I, three cases as stage II and one case was classified as stage III. Nine cases had initially been treated with simple curettage, one had aggressive curettage applied as a primary surgery and one underwent amputation. Among the nine simple curettage cases, one recurred and was reoperated with aggressive curettage. Adjuvant treatment (alcohol and/or cement) was applied in the two aggressive curettage cases; none demonstrated further tumour recurrence. All lesions were curettaged, and one case recurred. The rate of proliferating-cell nuclear antigen expression was significantly higher in the recurrent case. The recurrent case seemed to have a high growth activity. Simple curettage was effective for local control during the initial treatment in most cases, but aggressive curettage and adjuvant treatment with alcohol and/or cement was useful for local control in recurrent chondroblastoma and chondroblastoma presenting with an aggressive behaviour.
Eleven patients, three males and eight females, developed brain metastases from well-differentiated thyroid carcinoma 1 to 20 years after their original diagnosis. Two had brain metastases only and nine had metastases to the lungs and bones as well. Most patients died within a year of diagnosis of brain metastases. We conclude that brain metastasis from thyroid carcinoma carries a poor prognosis and that newer modalities of therapy may be needed.
Background: This report examines the patterns of presentation, prognostic factors and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over an 11-year period. Methods: A retrospective review of a prospectively collected database of all patients with GBC presenting between January 1998 and December 2008 was performed. Results: 102 GBC-patients were included: 69 women and 33 men (median age: 65,5 years). Forty-five patients presented with incidental gallbladder cancer (IGC) and 57 with nonincidental cancer (NIGC). Curative surgery rate was 84.4% for IGC and 29.8% for NIGC (p < 0.001). Five-year actuarial survival rate was 63.2% for patients with curative intent surgery and 0% for patients with palliative approach. Patients with IGC had a longer survival rate compared to patients with NIGC (median: 25.8 vs. 4.4 months, p < 0.0001). For patients with radical resection (42 patients), there was no difference between IGC and NIGC. The incidence of liver involvement was respectively 0%, 20.8%, 58.3%, 100% for pT1, pT2, pT3 and pT4 tumors. Univariate analysis showed that survival rate was significantly affected by perineural invasion, T, N and M-stage, R0 resection, liver involvement, CA-19.9. In multivariate analysis, liver involvement was the only independent factor. Conclusions: Majority of patients with a potentially curable disease had IGC. Almost 80% of patients with NIGC presented with unresectable disease. For patients who underwent resection with curative intent, actuarial 5-year survival was 63.2%. Liver involvement was the only independent prognostic factor. All patients with IGC and a pT2 or more advanced T stage should undergo a second radical resection.
The ameloblastoma is an uncommon benign odontogenic neoplasm of the maxillofacial region constituting less than 1% of tumours of the oral cavity. The purpose of this paper is to discuss and evaluate the surgical treatment and the outcome from a series of 11 patients with ameloblastomas. Between the years 1995 and 2003, 11 patients (eight female and three male) aged 17-86 years (mean 52.7) suffering from ameloblastomas of the jaws were seen in our Department. Ten patients were treated surgically. In eight of those radical surgery was applied. Patients with maxillary tumours were subjected to hemimaxillectomy and local excision. Radical treatment with segmental resection of the mandible was performed in six patients with multilocular (solid) mandibular ameloblastomas, with immediate reconstruction of the defect. Follow-up ranged from 3 months to 7.5 years. Multilocular (solid) type of tumours should be approached with radical surgical treatment. Enucleation and rarely marsupialization can be applied selectively to unilocular ameloblastomas.
We wanted to assess the factors that predict complications and patient satisfaction of totally implanted central venous access ports (TIAP). We reviewed 550 patients with breast or gynaecological malignancies who had initial port placement for chemotherapy between 1995 and 2006. We retrospectively assessed all TIAP complications, port duration and follow-up care until the TIAPs were removed (or the last known recorded documentation) or until the death of the patient. TIAP-related patient satisfaction was also assessed via a questionnaire-based survey of 356 patients. 561 TIAPs were placed in 550 cancer patients (11 patients received 2 TIAPs during the study period); the median time of port duration was 22.5 months. There were 104 complications in this group. Of these, 81 occurred during chemotherapy treatment that lasted a median time of 182 days. Removal secondary to complication was observed in 48 cases. TIAPs placed on the left chest side, through the subclavian vein or with the catheter tip localized in the peripheral part of superior vena cava demonstrated the highest incidence of complications. Patients with a BMI >28.75 had an increased risk for developing complications. Our follow-up questionnaire revealed a 93% patient satisfaction rate with the TIAP. Patients with left-sided ports, catheter tips lying in the upper part of the superior vena cava and implantation via the subclavian vein are at a higher risk for TIAP-associated complications. Being excessively overweight was assessed as another risk factor for developing complications. TIAPs are highly accepted and further recommended by patients.
The management of anastomotic leakage of the oesophago-jejunostomy after total gastrectomy for gastric carcinoma was evaluated in a retrospective study. Over a 30-year period, a total of 1114 oesophago-jejunostomies were performed during total gastrectomy for gastric cancer. In 83 cases (7.5%) a leak of the oesophago-jejunostomy was diagnosed. Frequency of anastomotic leakage was independent of the type of reconstruction and of surgical radicality. Therapeutic management was conservative in 58 cases (69.9%), with placement of a naso-jejunal tube along the anastomoses and with percutaneous drainage of intraabdominal abscesses. In 25 patients re-operation with resuturing of the anastomoses or surgical drainage of an abscess was performed. Mortality was 11/58 (19%) after conservative treatment of the anastomotic leakage and 16/25 (64%) after re-operation. Conservative management with a naso-intestinal tube and percutaneous drainage of intraabdominal abscesses is realistic for anastomotic leaks. Re-operation results in a high morbidity and should only be considered when conservative management is not successful.
The results of treatment of 1115 patients with colorectal cancer, from one hospital, are presented. The mean age of the patients was 67.24 (+/- 0.35 SEM) years and there were the same number of male and female patients. Forty per cent of patients were admitted as an emergency, and 67% of the tumours were in the rectum or sigmoid colon. 46.7% of the patients were considered to have undergone a 'curative' resection. Six per cent of the tumours were Dukes' Stage A lesions; 37% were Stage B and 57% Stage C. Twenty-six per cent had liver metastases. The overall hospital mortality was 21.5% and the operative mortality 14%. One-third of the patients admitted as an emergency died during their first admission. The overall 5-year survival was 25.8%; those with Dukes' Stage A tumours had a 5-year survival of 82.1%, Stage B 53.6% and Stage C 12.8%. The sex, site of tumour or duration of symptoms had no effect on prognosis.
The authors discuss the results of a diagnostic and therapeutic study of 112 cases of breast microcalcifications with no palpable lesions. The criteria in favor of obtaining a surgical specimen are discussed as a function of population characteristics and a review of the literature. Techniques for the localization of these lesions are defined. Decisions as to the necessity for ulterior treatment of the breast are based on certain criteria, and above all on the risk of evolution of invasive lesions with nodal involvement. The high quality of current mammograms has considerably increased the number of patients referred for biopsy. In the case of microcalcifications masking malignant lesions, the advances made in conservative treatment of breast cancer are not always applicable owing to the risks of failure with such conservative approaches.
This study evaluates the 3-year follow-up period and recurrence rate in patients with a negative sentinel node biopsy (SNB) without an additional axillary dissection (ALND). Between January 2000 and March 2002, 197 patients with an invasive breast cancer and clinically negative axillary nodes underwent a sentinel node biopsy. One hundred and thirteen patients were included in our study. The follow-up consisted of clinical examination every 3 months in the first year, followed by every 6 months after the first year. A mammography was obtained annually. Attention was paid to loco-regional recurrence, including axillary recurrence, and distant metastases. The mean duration of follow-up was 37.5 months (range 24-54). In this period, one patient was diagnosed with an axillary recurrence and one patient developed a supraclavicular lymph node metastasis. Two patients developed a second primary breast cancer in the contralateral breast. No patients were diagnosed with distant metastasis. These 3 year follow-up results suggest that SNB is a procedure with a low clinical recurrence rate, which can replace, when strict criteria are met, ALND if the sentinel node is negative.
Cholecystectomy has been connected with an increase in colorectal, breast and reproductive system cancers. On 472 patients, 398 women and 74 men, cholecystectomized during the years 1951 to 1955, cancer incidence was investigated. Our results show an elevated risk of breast cancer in the female group (P = 0.016), but no significant increased risk in colorectal or gynaecologic cancer. The risk for breast cancer increased with time after operation. In our small group of men an elevated SMR was noted for colon cancer without reaching statistical significance. Possible aetiological factors for the association between cholecystectomy and breast cancer are discussed.
We retrospectively evaluated the management of supraglottic carcinoma at our centre during the last 35 years to determine the preferred mode of treatment. A review of the medical records yielded 114 patients with supraglottic T1 and T2 carcinoma who were diagnosed and treated in the Departments of Otolaryngology, Head and Neck Surgery, and Oncology between 1959 and 1993. Of these, 47 (41.2%) had T1 carcinoma (stage I) and 67 (58.8%) T2 (stage II). Treatment varied among radiotherapy, surgery, or combined radiotherapy and surgery. Twelve patients underwent elective neck dissection, one of whom (8.3%) was found to have occult metastases. Local failures were noted in 22 patients (11 T1: 11 T2), three of whom also had neck metastases. All except one T2 patient received radiotherapy. Radiotherapy yielded the best survival rates for T1 disease as combined therapy did for T2. Five-year recurrence rates for T1 patients were 35% for those treated by radiotherapy and 42% for those treated with combined therapy; corresponding figures for T2 patients were 39% and 28%. We suggest that patients with T1 supraglottic carcinoma be managed with radiotherapy and patients with T2 with combined therapy. We believe there is no need for elective neck dissection, especially in T1.
One hundred and fourteen consecutive totally implantable catheters were inserted in 114 patients between April 1984 and April 1987. Catheters were inserted under neuroleptanalgesia, through the jugular vein in 101 cases or the internal saphenous vein in 13 cases. No problem was encountered during the insertion procedure. Infection occurred in 5.2% of the patients but removal of the device was required in only 2.6%. Occlusion of the catheter occurred in 6.1% of the patients but never during the first 2 months. This complication rate is lower than the one observed with external tunnelled catheters. The comfort of the patient is substantially improved and nursing care is greatly facilitated.
Perioperative morbidity and mortality were studied in 116 patients who underwent radical hysterectomy and lymph node dissection. Type II radical hysterectomy was performed in two, type III in 97, type IV in 12 and type V in five patients, and the perioperative morbidity was assessed accordingly. Because of the short follow-up time the late sequelae could not be evaluated. There was no operative death. Haemorrhage was the most common complication and it was more frequent and serious in type IV and V classes. Prolonged bladder atony was also frequent, particularly in type IV radical hysterectomy. The infection rate was comparable. One patient developed ureteric fistula, and one woman had ureteric stricture. Lymphocyst formation, nerve damage, lymphoedema and thromboembolic disease were rarely encountered and there was no bowel obstruction. Injury to the great vessels was a major problem. It appears that the rate of complications in this study is acceptable and comparable with or favourable to other reported series. In spite of this, every effort should be made to reduce the operative morbidity as far as possible.
The Subclavian vein has been traditionally the vein of choice for central venous catheterization by general surgeons. Alternative settings for the introduction of totally implantable venous access devices (TIVAD) and the search for lower rates of morbidity led to the choice of other central veins. This study compares two different venous accesses, the subclavian (SC) versus the internal jugular (IJ), in terms of early and late morbidity. This is a prospective, non-randomized, observational, uni-institutional (tertiary cancer centre) study. From March 2003 to March 2006, 1231 TIVADs were placed (1201 patients), in an ambulatory operating room, under vital signs and EKG monitoring, using local anaesthesia and without perioperative radiological control. Of the 1231 TIVAD, 617 were inserted via the SC and 614 via the IJ vein. The two groups (SC vs. IJ) were comparable as to general patient characteristics. Immediate complications were more frequent in the SC than in the IJ approach (respectively, 5.0% vs. 1.5%; p<0.001); Catheter malposition occurred in 2.3% when using the SC vein and in 0.2% for the IJ (p=0.001). Long term morbidity was also more frequent in the SC than in the IJ group (respectively, 15.8%, 87/551, vs. 7.6%, 39/512; p<0.001). Venous thrombosis developed in 2.0% of patients with an SC TIVAD as compared to 0.6% with an IJ TIVAD (p=0.044). Catheter malfunction was significantly dependent on the vein used: SC - 9.4% vs. IJ - 4.3% (p=0.001). Our results support the preferential use of the Internal Jugular vein for the insertion of TIVAD.
Postoperative tumor-residual-mass is the most important prognostic factor in epithelial ovarian cancer (EOC). Aim of our study was to define risk factors for incomplete tumor resection in advanced primary EOC. A validated intraoperative documentation tool ("Intraoperative-Mapping of Ovarian-Cancer" = "IMO") was applied to systematically evaluate intraabdominal tumor dissemination pattern, maximal tumor load, tumor residuals and operative morbidity for all EOC-patients who underwent primary surgery in our institution during 09/2000-08/2009. Univariate- and multivariate analysis were performed to identify independent risk factors of incomplete tumor resection and operative complications. We evaluated 360 consecutive EOC-patients of FIGO-stage-III/IV. In 221(61%) patients a complete tumor resection could be obtained. In 50(14%) patients tumor residuals were <0.5 cm. Sixty (17%) patients developed a major (14%) complication. Multivariate analysis identified intestinal resection (OR:2.0; 95%CI:1.14-3.4; p = 0.01) and macroscopical tumor residuals (OR:0.5; 95%CI:0.2-1.2; p = 0.05) as independent predictors of major operative morbidity. Tumor dissemination pattern and maximal tumor load were significantly different between tumor-free and not-tumor-free operated patients, with less extrapelvic tumor involvement in the tumor-free group (p < 0.001). More than 4 IMO-fields of tumor involvement (OR:3.3; 95%CI:1.5-7.0; p = 0.002) were identified to be of predictive significance for incomplete tumor resection. FIGO-stage, histology, age, CA125-levels, bowel resection and ascites did not affect optimal tumor resectability. Tumor expanding in multiple (>4) abdominal quadrants was the major negative predictors for complete tumor resection in primary EOC-patients. Bowel resection and macroscopical tumor residuals were of predictive value for a higher operative major morbidity. Identifying high-risk patients for suboptimal tumor resection and operative complications may improve surgical outcome in advanced primary EOC.
A review of 1244 breast cancer cases from the Tumor Registry of Northwest Community Hospital between 1980 and 1995 was carried out to investigate the incidence of axillary metastasis. There were 442 patients (35.45%) with positive nodes. The small lesions were graded to ascertain if size and grade of small tumors can be used to predict axillary metastasis. One hundred and seventy-nine cases of < or = 1.0 cm were retrospectively reviewed by one pathologist. Tumors <0.4 cm had negative nodes. Those with nuclear and histologic grades of 1 had 3% positive nodes, the remainder had positive nodes ranging from 11% to 19%. Infiltrating duct cancers of nuclear grade 3, histologic grade 2, and positive nodes, showed a 40% mortality. Eighteen patients died in the 0.5-1.0 cm tumor size range, mostly of histologic grade 2 and nuclear grade 3. Nuclear and histologic grade 1 tumors with infiltrating duct cancers had negative nodes and showed a good prognosis. Based on this study, node dissection can be omitted in these patients and in those with tumors < or = 0.4 cm. For all other lesions, full axillary node dissection and detailed pathologic examination is still the gold standard for evaluating the axilla.
Top-cited authors
Harald Hoekstra
  • University of Groningen
Alexander Maximiliaan Eggermont
  • *Comprehensive Cancer Center Munich D; **Princess Maxima Center & University MC Utrecht NL; and ***DKFZ German Cancer Research Center Heidelberg D
Emiel J Rutgers
  • Netherlands Cancer Institute
Theo Wiggers
Cornelis Verhoef
  • Erasmus University Rotterdam