Wilt, J.H.W. de

Combined therapy for thyroid squamous cell carcinoma (Article)

2012-01-01T00:00:00Z

Background. Squamous carcinoma of the thyroid is a rare aggressive disease, resulting in poor prognosis. Methods. and Results. We combined cisplatin with paclitaxel on a weekly basis as induction therapy, achieving a high cumulative dose, in a patient with squamous cell tumor of the thyroid with arterial encasement. After surgery, pathologic examination confirmed a complete resection of the primary tumor with clear margins, revealing a successful induction treatment with chemotherapy. Conclusions. Our patient now has a recurrence-free survival of >20 months, longer than the mean survival described in the literature.

Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: A population-based series (Article)

2012-01-01T00:00:00Z

Aim The incidence, patterns of care and survival were determined in patients with stage IV colorectal cancer (CRC) in a population-based series. Method Computer records for patients diagnosed with stage IV CRC diagnosed from 1 January 1995 to 31 December 2007 were retrieved from the Rotterdam Cancer Registry. Surgical resection of the primary tumour, chemotherapy use, hepatic surgery and survival were evaluated according to year of diagnosis, age, gender and primary tumour site. Results In the southwestern part of the Netherlands, 19014 new patients with CRC were diagnosed and synchronous metastatic disease was found in 3482 (18%). This proportion increased during the study period, from 16% to 21%. Surgical resection of the primary tumour was performed in approximately 50% of the patients and did not change over time. Postoperative 30-day mortality was 8%. Chemotherapy use increased from 18% in the first period to 56% in the latest period. Liver surgery increased from 4% in the first period to 10% in the latest period. Median survival increased from 7months to 12months and 2-year survival increased from 14% to 28%. Two-year survival declined with increasing age and was significantly worse for right-sided tumours (14%). Conclusion Survival of patients with stage IV CRC has improved over time and this is probably a result of the increased use of chemotherapy and the increased numbers of patients who underwent hepatic surgery. © 2011 The Authors. Colorectal Disease

Long-term outcome of isolated limb perfusion with tumour necrosis factor-α for patients with melanoma in-transit metastases (Article)

2011-11-01T00:00:00Z

Background: The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. Methods: Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. Results: Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. Conclusion: ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma. Copyright

Treatment and prognostic significance of positive interval sentinel nodes in patients with primary cutaneous melanoma (Article)

2011-11-01T00:00:00Z

Background: Interval sentinel nodes (SNs) are lymph nodes receiving direct lymphatic drainage from a primary site and lying between the tumor and a recognized node field. It is not clear what further nodal surgery should be performed when interval nodes are found to contain micrometastatic disease. In this study, the incidence, location, and treatment of interval SNs in melanoma patients were analyzed to develop recommendations regarding the treatment of patients with interval SNs. Methods: A retrospective review was undertaken of all patients with primary cutaneous melanoma who underwent lymphoscintigraphy at a single institution between 1992 and 2007. Data concerning the primary melanoma, location of SNs, treatment and survival were analyzed. Results: Of 4895 patients who had a lymphoscintigram during the study period, 442 (9.0%) had an interval SN identified on lymphoscintigraphy. Interval SNs occurred significantly more often in patients with melanomas on the posterior trunk than in those with melanomas at other sites (P < 0.001). A total of 197 patients (44.6%) with an identified interval SN underwent excision biopsy of the node. Of the 16 patients found to have metastatic melanoma in their interval SN, four also had negative SNs in a recognized lymph node field, and no other positive nodes were found on completion lymphadenectomy. Conclusions: Interval SNs are present in approximately 1 in 10 melanoma patients but are about half as likely to contain metastases as SNs in recognized node fields. If a positive interval SN is found, completion lymphadenectomy of the recognized lymph node field is only recommended if a SN in this field is also positive.

Long-term results of tumor necrosis factor α- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas (Article)

2011-10-20T00:00:00Z

Purpose: Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS. Patients and Methods: We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors. Results: The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P<.001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%. Conclusion: We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.

Surgery of the primary in stage IV colorectal cancer with unresectable metastases (Article)

2011-09-01T00:00:00Z

Surgery plays an important role in the treatment of patients with limited metastatic disease of colorectal cancer (CRC). Long term survival and cure is reported in 20-50 of highly selected patients with oligometastatic disease who underwent surgery. This paper describes the role of surgery of the primary tumour in patients with unresectable stage IV colorectal cancer. Owing to the increased efficacy of chemotherapeutic regimens in stage IV colorectal cancer, complications from unresected primary tumours are relatively infrequent. The risk of emergency surgical intervention is less than 15 in patients with synchronous metastatic disease who are treated with chemotherapy. Therefore, there is a tendency among surgeons not to resect the primary tumour in case of unresectable metastases. However, it is suggested that resection of the primary tumour in case of unresectable metastatic disease might influence overall survival. All studies described in the literature (n = 24) are non-randomised and the majority is single-centre and retrospective of nature. Most studies are in favour of resection of the primary tumour in patients with symptomatic lesions. In asymptomatic patients the results are less clear, although median overall survival seems to be improved in resected patients in the majority of studies. The major drawback of all these studies is that primarily patients with a better performance status and better prognosis (less metastatic sites involved) are being operated on. Another limitation of these studies is that few if any data on the use of systemic therapy are presented, which makes it difficult to assess the relative contribution of resection on outcome. Prospective studies on this topic are warranted, and are currently being planned. Surgery of the primary tumour in patients with synchronous metastasised CRC is controversial, although data from the literature suggest that resection might be a positive prognostic factor for survival. Therefore prospective studies on the value of resection in this setting are required.

Erratum: High tie versus low tie in rectal surgery: Comparison of anastomotic perfusion (Int J Colorectal Dis DOI 10.1007/s00384-011-1188-6) (Article)

2011-06-01T00:00:00Z

Outcome After Therapeutic Lymph Node Dissection in Patients with Unknown Primary Melanoma Site (Article)

2011-05-25T00:00:00Z

Purpose: The aim of this study was to evaluate the incidence and outcome of melanoma of unknown primary site (MUP) after therapeutic lymph node dissection (TLND) of palpable nodal melanoma metastases. Disease-free (DFS) and overall survival (OS) time of MUP patients were analyzed and compared to patients undergoing a TLND for known primary melanomas (MKP). Methods: This single institution retrospective study analyzed 342 consecutive patients who were treated with 415 TLNDs for palpable nodal disease from 1982 to 2009. Univariate and multivariate analyses included: MUP versus MKP, gender, Breslow thickness, ulceration of primary tumor, site of primary tumor, site of dissection, extracapsular extension, number of collected nodes, number of positive nodes and the node positive ratio. Results: A total of 47 MUP were identified in 342 patients (13.7%). In univariate analysis, a trend was seen toward better survival for MUP patients compared to MKP patients having 5-year OS rates of 40% and 27%, respectively (P = 0.06). Multivariate analysis for OS showed two highly significant factors associated with worse prognosis: extracapsular extension and N3 status (both P < 0.001). Two factors were associated with a significant better prognosis: MUP (P = 0.03) and a neck dissection (P = 0.04). Conclusions: Patients with MUP showed a statistically significant better OS compared to patients with melanoma metastases from known primary tumors. Presence of extracapsular extension and an increased number of positive nodes are statistically significantly negative prognostic factors for OS. The absence of a primary melanoma in stage III melanoma patients does not preclude surgery.

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection (Article)

2011-05-03T00:00:00Z

Background: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. Methods: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. Results: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. Conclusions: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.

Prevalence and prognosis of synchronous colorectal cancer: A Dutch population-based study (Article)

2011-04-05T00:00:00Z

Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29-1.84) and in patients aged >70 years (OR 1.83, 95% CI 1.39-2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27-2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery.

High tie versus low tie in rectal surgery: comparison of anastomotic perfusion (Article)

2011-03-29T00:00:00Z

Purpose: Both "high tie" (HT) and "low tie" (LT) are well-known strategies in rectal surgery. The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT. Methods: Patients undergoing rectal resection for malignancy were included. Colonic perfusion was measured with laser Doppler flowmetry, immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop (measurement A). This measurement was repeated after rectal resection (measurement B). The blood flow ratios (B/A) were compared between the HT group and the LT group. Results: Blood flow was measured in 33 patients, 16 undergoing HT and 17 undergoing LT. Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group. The blood flow ratio was significantly higher in the LT group (1.48 vs. 0.91; p = 0.04), independent of the blood pressure. Conclusion: This study shows the blood flow ratio to be higher in the LT group. This suggests that anastomoses may benefit from better perfusion when LT is performed.

Dysphagia after an L-shaped reconstruction technique of the free jejunum graft (Article)

2010-11-01T00:00:00Z

Background: The free jejunum graft is a well-established reconstruction technique after total laryngopharyngectomy. However, besides necrosis of the jejunum graft, the two most important complications are pharyngocutaneous fistula formation and dysphagia due to stricture formation. Objectives: This study aims to develop an L-shaped reconstruction technique of the free jejunum graft to decrease pharyngocutaneous fistula formation and long-term stricture formation after total laryngopharyngectomy. Methods: An L-shaped side-to-end anastomosis was performed at the proximal end of the jejunum graft in six patients treated for piriform sinus carcinoma. Patient and operation characteristics and follow-up were recorded. Results: A successful jejunum transfer was performed in all six patients. No pharyngocutaneous fistula or stricture formation occurred during a median follow-up of 23 months (range: 18-30 months). Swallowing rehabilitation started at the median 12th postoperative day (range: 5-150 days). Four patients developed dysphagia at a median of 2 months (range: 1-6 months) after oral intake was started. X-barium swallow revealed a redundant pouch of the transferred jejunum graft, which resulted in compression on the jejunum interposition during swallowing. In three patients, an operation was required to resolve these problems. After the revision operation, no dysphagia occurred during a median follow-up of 12 months (range: 7-13 months). Conclusions: Because of dysphagia complaints in the majority of our patients, we cannot recommend the described technique and should find other means to improve direct postoperative results and long-term quality of life in this difficult-to-treat group of patients.

Trends in treatment for synchronous colorectal liver metastases: Differences in outcome before and after 2000 (Article)

2010-10-01T00:00:00Z

Background: The traditional treatment for stage IV colorectal cancer has changed from palliative chemotherapy toward an aggressive multimodality approach. In the current study outcome in patients who underwent surgery for synchronous colorectal liver metastases (CLM) in a single center was evaluated. Methods: From January 1991 to May 2008 all consecutive patients with synchronous CLM who underwent curative resection of both primary and metastatic disease were included. Date of resection was divided into two groups: date of hepatic resection before and after the year 2000. Results: Fifty patients (26%) with synchronous CLM were resected before 2000 and 142 patients (74%) underwent resection after 2000. The estimated 5-year disease-free survival before and after 2000 was 9% and 27%, respectively (P = 0.379). More patients who underwent resection after 2000 were treated with local therapy or underwent resection for intra-hepatic recurrence (62% vs. 28%, P = 0.033). The estimated 5-year survival before and after 2000 was 26% and 44%, respectively (P = 0.001). Conclusion: Survival rates in patients with synchronous CLM have been increased in the past decade. The introduction of new chemotherapeutic drugs and a more aggressive treatment approach in patients with liver recurrence were probably major factors in this progress.

'Staged' liver resection in synchronous and metachronous colorectal hepatic metastases: Differences in clinicopathological features and outcome (Article)

2010-10-01T00:00:00Z

Aim: Approximately 25% of the patients with colorectal cancer already have liver metastases at diagnosis and another 30% will develop them subsequently. The features and prognosis of patients with synchronous and metachronus colorectal liver metastases, treated with primary resection first followed by partial liver resection were analysed. Method: Curative staged resection of liver metastases was performed in 272 consecutive patients. Demographics, characteristics of the primary tumour and metastatic tumours, surgery-related data and outcome were analysed. Results: Synchronous metastases were present in 105 (39%) patients and metachronous metastases in 167 (61%). More patients in the synchronous group had an advanced primary tumour (T3/T4 and/or node positivity), more than three liver metastases and bilobar distribution. A significantly higher percentage of patients in the synchronous group received neoadjuvant chemotherapy. The 5-year survival rate in the group of 272 patients was 38%. Patients with more than three metastases had a significantly worse survival rate. There were no differences in disease-free and overall survival rates between the synchronous and metachronous group. Conclusion: Although patients with synchronous colorectal liver metastases may have poorer biological features, there was no difference in 5-year disease-free and overall survival compared with patients with metachronous metastases. This may be explained by the observation that patients in the synchronous group received significantly more neoadjuvant chemotherapy. © 2010 The Authors. Colorectal Disease

Early and long-term morbidity after total laryngopharyngectomy (Article)

2010-09-01T00:00:00Z

To determine the early and long-term morbidity of patients treated with a total laryngopharyngectomy and reconstruction using a jejunum interposition or gastric pull-up procedure. It is a retrospective study; and it is conducted in tertiairy referral center. Sixty-three patients were included in whom 70 reconstructions were performed (51 jejunum interpositions and 19 gastric pull-up procedures) between 1990 and 2007. The studied parameters were success rate of the reconstruction, early and long-term complication rate, and functional outcome including quality of life. Subjective quality of life analysis was determined by two questionnaires: the EORTC Quality of Life Questionnaire (QLQ)-C30 Dutch version 3.0, and the EORTC-Head and Neck (H & N 35). The success rates were 84 and 74%, respectively. The procedures were associated with a high complication rate (63% after jejunum interposition and 89% after gastric pull-up), and a lengthy rehabilitation. Surviving patients were found to have a good long-term quality of life. Complete oral intake was achieved in 97%, and speech rehabilitation in 95%. These procedures are associated with significant morbidity, high complication rates, lengthy rehabilitation, but a good long-term quality of life.

Local excision of rectal cancer afterchemoradiation: Feasibility depends on the primary stage (Article)

2010-09-01T00:00:00Z

Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer (Article)

2010-09-01T00:00:00Z

PURPOSE: The aim of this study was to evaluate the management and outcome of local recurrences after transanal endoscopic microsurgery for T1 rectal cancer. METHODS: Consecutive patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer at a Dutch referral center (IJsselland Hospital) were registered in a prospective database. Follow-up was according to Dutch guidelines on rectal cancer, with additional rigid rectoscopy and endorectal ultrasound examinations every 3 months for the first 2 years, and every 6 months thereafter. Annual MRI of the lesser pelvis was added during the last 2 years of the study. Patients with local recurrence during follow-up were selected for individual analysis of outcome. RESULTS: Of a total of 88 patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer, 18 patients (20.5%) had a local recurrence. Median time to local recurrence was 10 (range, 4-50) months. Medial age at diagnosis of recurrence was 74 (range, 56-84) years. Of the 18 patients, 2 did not undergo further surgery because of concomitant metastatic disease, and 16 underwent salvage surgery, without need for multivisceral resections. No postoperative mortality was observed. In 15 patients (94%), a microscopically negative excision margin was obtained; in 1 patient, the excision margin was microscopically positive. Median follow-up after salvage surgery was 20 (range, 2-112) months. One patient had a local renewal of recurrence, and 7 patients (39%) had distant metastases. At 3 years, overall survival was 31%; cancer-related survival was 58%. CONCLUSIONS: Recurrent disease after transanal endoscopic microsurgery for T1 rectal cancer is a major problem. Although salvage surgery for achieving local control is feasible in most patients, survival is limited, mainly because of distant metastases. Tailoring selection of T1 rectal cancers and exploring possible adjuvant treatment strategies following salvage procedures should be the next steps toward improving survival.

Cervical lymph node dissection for metastatic testicular cancer (Article)

2010-06-01T00:00:00Z

Introduction. Despite high response rates to systemic chemotherapy, 30% of patients with advanced stage testicular carcinoma will have extra- retroperitoneal residual masses that require resection. Most often, these are located in the lungs and mediastinum and neck. Limited data are available concerning the incidence, surgical management, and follow-up of neck metastasis arising from a testicular primary tumor. Methods. We retrospectively reviewed all 665 patients who were referred to a tertiary referral center with the diagnosis of testicular cancer from January 1997 to June 2009 for the presence of cervical metastases. Patients who underwent concomitant surgical therapy were identified and analyzed. Clinical and pathological data were collected from patient records, including radiology and pathology reports. Furthermore, data on primary treatment strategy, chemotherapeutic regimens, timing of surgical procedures, complications, disease recurrence, and follow-up were collected. Results. Twenty-six patients (4%) had cervical lymph node metastasis. The majority (n = 19) had multiple ERP sites. Nine patients (35%) underwent selective neck dissection: in six patients, this was indicated because of residual masses after chemotherapy, and in three patients, cervical masses represented a late and distant relapse of previously treated disease. Viable cancer cells were present in the resected specimen only in these three patients. Seven patients are currently without evidence of disease. Two patients died of disseminated disease. Conclusions. Cervical lymph node metastases originating from testicular cancer are rare but are more commonly observed in patients with advanced stage disease. Selective neck dissection can be safely performed both after chemotherapy and in the case of recurrent disease.

Salvage or what follows the failure of a free jejunum transfer for reconstruction of the hypopharynx? (Article)

2010-06-01T00:00:00Z

Aim: To analyse the cases of failure of free jejunum transfer with subsequent secondary reconstruction methods after ablative surgery for malignant tumours of the laryngopharyngeal region and the cervical oesophagus with reconstruction using a jejunum interposition. Materials and methods: Four cases in which failure of the jejunum interposition was managed with a second free or pedicle transfer were identified. The electronic files of patients were studied and analysed for patient characteristics and failure of reconstruction; type of salvage surgery and outcome; swallowing function and rehabilitation; postoperative complications; recurrence of tumour; patient survival and cause of death. Results: Failure of the interposition occurred within 11 days in all patients, with oral bleeding being the most prominent sign. To replace the failed jejunum transfer, two new free jejunum transfers, two gastric pull-ups and one colon interposition after the second failure of a jejunum transfer were used. Three patients started swallowing rehabilitation, of which two achieved complete oral intake, defined as the redundancy of a feeding tube. The median disease-free period and overall survival was 28 and 42 months, respectively. Conclusion: Failure of a free jejunum transfer is a rare but inevitable complication when performed in a high-risk patient population, with oral bleeding being the most important sign of necrosis. Salvage of the buried jejunum interposition is hardly ever possible and secondary reconstruction can be performed using a new jejunum interposition or gastric pull-up procedure with considerable early postoperative complications, but relatively good results regarding swallowing rehabilitation and patient survival.

Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases (Article)

2010-03-01T00:00:00Z

Background: This study evaluated the outcome of patients treated tor rectal cancer and synchronous hepatic metastases in the era of effective induction radiotherapy and chemotherapy. Methods: All patients undergoing surgical treatment of rectal cancer and synchronous liver metastases between 2000 and 2007 were identified retrospectively from a prospectively collected database. Three approaches were followed: the classical staged, the simultaneous and the liver-first approach. Results: Of 57 patients identified, the primary tumour was resected first in 29 patients (group 1), simultaneous resection was performed in eight patients (group 2), and 20 patients underwent a liver-first approach (group 3). The overall morbidity rate was 24-6 per cent; there was no in-hospital mortality. Median in-hospital stay was significantly shorter for the simultaneous approach (9 days versus 18 and 15 days for groups 1 and 3 respectively; P < 0.001). The overall S-year survival rate was 38 per cent, with an estimated median survival of 47 months. Conclusion: Long-term survival can be achieved using an individualized approach, with curative intent, in patients with rectal cancer and synchronous liver metastases. Simultaneous resections as well as the liver-first approach are attractive alternatives to traditional staged resections.

Abdominosacral resection for locally advanced and recurrent rectal cancer (Article)

2009-11-01T00:00:00Z

Background: The results of resection of locally advanced and recurrent rectal cancers, including sacral resection, were analysed critically. Methods: Between 1987 and 2007, 353 patients with locally advanced or recurrent rectal cancer, all treated in a tertiary referral centre, were identified from a prospective database. Twenty-five patients (eight primary and 17 recurrent tumours) underwent en bloc sacral resection. Results: A mid-sacral resection was carried out in 12 patients (level S3) and a low sacral resection in 13 (level S4/S5). Nineteen patients had an R0, four an R1 and two an R2 resection. There was no postoperative mortality. Median follow-up was 32 months. Incomplete resection had an independent negative influence on local control (5-year local recurrence rate 42 versus 0 per cent in those with and without incomplete resection; P < 0.001). The 5-year overall survival rate was 30 per cent. Five patients with recurrent tumour had pathological invasion into the sacral bone and none survived beyond 1 year. Conclusion: Abdominosacral resection can be performed in patients with locally advanced and recurrent rectal cancer. Patients who cannot undergo a complete resection or have clear evidence of cortical invasion have a poor prognosis. Copyright

Preoperative radiotherapy has no value for patients with T2-3, n0 adenocarcinomas of the rectum (Article)

2009-10-01T00:00:00Z

Background: Treatment of rectal cancer with preoperative radiotherapy followed by total mesorectal excision is nowadays the standard treatment. It reduces local recurrences and improves overall survival. However, in patients with T2-3, N0 rectal cancer, the role of preoperative radiotherapy remains controversial. The aim of this study was to review the benefit of radiotherapy in T2 and T3, N0 rectal cancer patients. Methods: Between 1996 and 2003, 103 patients with T2-3, N0 rectal cancer were identified in our prospective database. This study evaluated time to local recurrence, distant metastases and overall survival. Results: Median follow-up was 4.3 years. The 5-year local control rate was 94%. The 5-year overall survival was 65%. The 5-year disease-free survival rate was 82%. Preoperative radiotherapy did not show any statistical differences. Abdominal perineal resection and T3 tumors negatively influenced overall survival (p = 0.02). Advanced age was of significant importance in overall survival. Conclusions: Preoperative radiotherapy does not seem to be of significant importance in patients with T2-3, N0 rectal cancer regarding local recurrence and survival. Since preoperative radiotherapy is associated with short- and long-term morbidity, patients with T2-3, N0 tumors should be identified and treated with surgery alone.

Isolated limb perfusion with TNF-α and melphalan in locally advanced soft tissue sarcomas of the extremities (Article)

2009-08-21T00:00:00Z

Limb-sparing surgery has become all the more important in soft tissue sarcoma (STS) of the extremities since we learned that amputation does not improve survival of these patients. In bulky tumours, however, preoperative strategies to reduce tumour size are then required. Isolated limb perfusion (ILP) with tumour necrosis factor (TNF) has been developed as a biochemotherapeutic therapy to act both on the tumour-associated vasculature and on the tumour itself. It has shown to be a very potent treatment modality, as in early reports response rates were around 80%. Limb salvage could then be achieved in a quite similar percentage. Many confirmatory studies have been performed since, with consistent results even in patients with multiple tumours, after extensive radiotherapy or with metastatic disease, all at the cost of very limited toxicity. This chapter gives an overview of the ILP studies performed in patients with soft tissue limb sarcoma, discusses the mechanism of TNF-mediated vasculotoxic effects on tumour vasculature, and places TNF-based ILP in the multimodality treatment of these patients with extensive STS of the extremities.

Total pelvic exenteration for primary and recurrent malignancies (Article)

2009-07-01T00:00:00Z

Introduction: Complete resection is the most important prognostic factor in surgery for pelvic tumors. In locally advanced and recurrent pelvic malignancies, radical margins are sometimes difficult to obtain because of close relation to or growth in adjacent organs/structures. Total pelvic exenteration (TPE) is an exenterative operation for these advanced tumors and involves en bloc resection of the rectum, bladder, and internal genital organs (prostate/seminal vesicles or uterus, ovaries and/or vagina). Methods: Between 1994 and 2008, a TPE was performed in 69 patients with pelvic cancer; 48 with rectal cancer (32 primary and 16 recurrent), 14 with cervical cancer (1 primary and 13 recurrent), 5 with sarcoma (3 primary and 2 recurrent), 1 with primary vaginal, and 1 with recurrent endometrial carcinoma. Ten patients were treated with neoadjuvant chemotherapy and 66 patients with preoperative radiotherapy to induce down-staging. Eighteen patients received IORT because of an incomplete or marginal complete resection. Results: The median follow-up was 43 (range, 1-196) months. Median duration of surgery was 448 (range, 300-670) minutes, median blood loss was 6,300 (range, 750-21,000) ml, and hospitalization was 17 (range, 4-65) days. Overall major and minor complication rates were 34% and 57%, respectively. The in-hospital mortality rate was 1%. A complete resection was possible in 75% of all patients, a microscopically incomplete resection (R1) in 16%, and a macroscopically incomplete resection (R2) in 9%. Five-year local control for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 89%, 38%, and 64%, respectively. Overall survival after 5 years for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 66%, 8%, and 45%. Conclusions: Total pelvic exenteration is accompanied with considerable morbidity, but good local control and acceptable overall survival justifies the use of this extensive surgical technique in most patients, especially patients with primary locally advanced rectal cancer and recurrent cervical cancer.

Multimodality treatment for anaplastic thyroid carcinoma - Treatment outcome in 75 patients (Article)

2009-07-01T00:00:00Z

Purpose: To retrospectively analyze the outcome of patients with anaplastic thyroid carcinoma (ATC) treated in the Erasmus MC. Material and methods: Seventy-five ATC-patients were treated between 1972 and 2003. Mean age was 68 years. Tumor stage was IVA in 9%, IVB in 51%, and IVC in 40%. Thirty-six patients underwent up-front surgery, with 53% resulting in R0/R1 resection. Before 1988 adjuvant treatment consisted of conventional radiotherapy (RT) and/or chemotherapy (CT). As of 1988, 30 eligible patients were enrolled in a newly designed protocol. This consists of locoregional RT in 46 fractions of 1.1 Gy, given twice daily, followed by prophylactic irradiation of the lungs (PLI) in 5 daily fractions of 1.5 Gy. During radiation, low-dose Doxorubicine (15 mg/m2) is administered weekly and is followed by adjuvant Doxorubicine (50 mg/m2) 3-weekly up to a cumulative dose of 550 mg/m2. Twenty-five ineligible patients were treated conventionally. Results: Overall median survival was 3 months, 1-year OS 9%. Locoregional control was significantly higher in patients who had undergone R0/R1 resection or chemoradiation, with best results for patients who underwent both (complete remission in 89%). However, the survival benefit of patients who reached CR remained borderline (median OS 7 months, 1-year OS 32%). Three patients survived for more than 5 years; all had undergone R0/R1 surgical resection and chemoradiation. Acute toxicity in the protocol group was significantly higher than in the nonprotocol group, with 46% versus 11% grade 3 pharyngeal and/or esophageal toxicity. Conclusion: Despite the ultimately dismal prognosis of ATC-patients, multimodality treatment significantly improved local control and improved the median survival.

Total mesorectal excision for rectal cancer in an unselected population: Quality assessment in a low volume center (Article)

2009-06-05T00:00:00Z

Objective: The aim of this study was to review the results and long-term outcome after total mesorectal excision (TME) for adenocarcinoma of the rectum in an unselected population in a community teaching hospital. Materials and methods: Between 1996 and 2003, 210 patients with rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathological reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed. Results: The mean age at diagnosis was 69 years (range 40-91 years). A total of 145 patients were treated by anterior rectal resection; 65 patients had to undergo an abdominoperineal resection (APR). Anastomotic leakage rate was 5%. Postoperative mortality was 3%. After a median follow-up of 3.6 years, the local recurrence-free rate in patients with microscopically complete resections was 91%. The 5-year overall survival rate was 58%. An increased serum carcinoembryonic antigen, an APR, positive lymph nodes, and an incomplete resection all significantly influenced the 5-year overall survival and local recurrence rate. In a multivariate analysis, age was the most important prognostic factor for overall survival. Conclusions: Patients with rectal cancer can safely be treated with TME in a community teaching hospital and leads to a good overall survival and an excellent local control. In patients aged above 80, treatment-related mortality is an important competitive risk factor, which obscures the positive effect of modern rectal cancer treatment.

Local treatment for recurrent colorectal hepatic metastases after partial hepatectomy (Article)

2009-05-01T00:00:00Z

Objective: The objective of the study was to identify patients who may benefit from local treatment in recurrent colorectal liver metastases. Materials and methods: A total of 51 consecutive patients were treated for hepatic recurrence(s) after an initial partial hepatic resection. Surgery was considered as the primary treatment option for eligible patients. Patients with a small liver remnant after major hepatectomy were treated with radiofrequency ablation (RFA) or stereotactic body radiation therapy (SRx). SRx was given as an outpatient, emerging local treatment option for patients with intra-hepatic recurrences not eligible for surgery or RFA. Partial liver resection was performed in 36 patients (70%), RFA in ten patients (20%), and SRx in five patients (10%). Results: Median hospital stay was 7 (range, 3-62) days with a morbidity of 16% without in-hospital death. None of the patients received adjuvant chemotherapy. There was no difference in recurrence or survival between the three treatment modalities. Overall 5-year survival was 35% with an estimated median survival of 37 months. Patients with a disease-free interval between first hepatectomy and hepatic recurrence less than 6 months did not survive 3 years. Conclusions: Resection, RFA, and SRx can be performed safely in patients with recurrent colorectal liver metastases and offer a survival that seems comparable to primary liver resections of colorectal liver metastases.

Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases (Article)

2009-05-01T00:00:00Z

Aim: Ocular melanoma prefers to metastasize to the liver and the liver is the sole site of metastatic disease in 80% of patients. Until now there has been no standard treatment available and these patients have a very poor prognosis (median survival 2-5 months). Isolated hepatic perfusion may be an option in patients with irresectable hepatic ocular melanoma metastases. The aim of this study was to evaluate applicability, toxicity and response in this selected group of ocular melanoma patients by treatment with isolated hypoxic hepatic perfusion with retrograde outflow (IHHP) with melphalan. Methods: From September 2002 until July 2006 eight consecutive patients were included in this study. IHHP was performed with inflow via the hepatic artery and retrograde outflow via the portal vein during 25 min with 1 mg/kg melphalan. The perfusion was followed by a complete wash-out procedure. Results: The median total operation time was 4 h with a median blood/fluid loss of 1100 ml. No postoperative mortality was observed. Median hospital stay was 9.5 days. Toxicity was moderate: WHO grade 3 leukocytopenia in 3 patients, grade 3 hepatic toxicity in 1 patient. In 37% of patients (3/8) a partial response could be demonstrated 3 months after IHHP. Stable disease was found in 3 patients and progressive disease in 2 patients. Median time to local progression was 6 months and the median survival was 11 months. Conclusion: Melphalan-based IHHP with retrograde outflow is a safe treatment option for patients with irresectable ocular melanoma metastases. Survival benefit seems to be comparable to classical IHHP.

Underutilization of microsatellite instability analysis in colorectal cancer patients at high risk for lynch syndrome (Article)

2009-05-01T00:00:00Z

Objective. The revised Bethesda Guidelines were published to improve the efficiency of recognizing Lynch syndrome (LS) by identifying LS-related malignancies that should be analyzed for microsatellite instability (MSI). The aim of this study was to evaluate whether MSI analysis was performed in colorectal cancer patients at risk for LS according to the revised Bethesda Guidelines. Material and methods. Patients diagnosed with colorectal cancer in 11 Dutch hospitals in 2005 and 2006 were selected from a regional database. The patients were included in the study if they met any of the following criteria; 1) diagnosed with colorectal cancer 50 years, 2) a second LS-associated tumor prior to the diagnosis of colorectal cancer in 2005/2006, and 3) colorectal cancer 60 years with a tumor displaying mucinous or signet-ring differentiation or medullary growth pattern. Results. Of 1905 colorectal cancer patients, 169 met at least one of the inclusion criteria. MSI analysis had been performed in 23 (14%) of the 169 tumors. MSI status had been determined in 18 of 80 included patients aged 50 years, in 4 of 70 patients with a second LS-related tumor, and in 3 of 41 patients aged 60 years with high-risk pathology features. Conclusions. There is marked underutilization of MSI analysis in patients at risk for LS. As a result LS might be underdiagnosed both in patients with colorectal cancer and in their relatives.

The "liver-first approach" for patients with locally advanced rectal cancer and synchronous liver metastases. (Article)

2009-01-01T00:00:00Z

PURPOSE: This study was designed to investigate the outcome of "the liver-first" approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver metastases. If successful, patients underwent treatment for the rectal tumor. RESULTS: Twenty-three patients were included. One patient had liver resection without neoadjuvant chemotherapy followed by chemoradiotherapy. All remaining 22 patients underwent laparotomy after chemotherapy. Eighteen patients underwent partial liver resection and subsequent chemoradiotherapy for the rectal cancer. One patient underwent in one session a partial liver resection and a low anterior resection. Six patients were not treated according to protocol because of extensive disease. Sixteen patients (73 percent) completed the full treatment protocol and all are alive after a median period of 19 (range, 7-56) months. CONCLUSIONS: This is the first sizable report on the "liver-first approach" demonstrating that it may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases. It allows most patients to undergo curative resections of both metastatic and primary disease and can avoid useless rectal surgery in patients with incurable metastatic disease.

The 'liver-first approach' for patients with locally advanced rectal cancer and synchronous liver metastases (Article)

2009-01-01T00:00:00Z

PURPOSE: This study was designed to investigate the outcome of ''the liver-first'' approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver metastases. If successful, patients underwent treatment for the rectal tumor. RESULTS: Twenty-three patients were included. One patient had liver resection without neoadjuvant chemotherapy followed by chemoradiotherapy. All remaining 22 patients underwent laparotomy after chemotherapy. Eighteen patients underwent partial liver resection and subsequent chemoradiotherapy for the rectal cancer. One patient underwent in one session a partial liver resection and a low anterior resection. Six patients were not treated according to protocol because of extensive disease. Sixteen patients (73 percent) completed the full treatment protocol and all are alive after a median period of 19 (range, 7Y56) months. CONCLUSIONS: This is the first sizable report on the ''liver-first approach'' demonstrating that it may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases. It allows most patients to undergo curative resections of both metastatic and primary disease and can avoid useless rectal surgery in patients with incurable metastatic disease.

The Rotterdam criteria for sentinel node tumor load: the simplest prognostic factor? (Letter To Editor)

2008-12-01T00:00:00Z

Sentinel node tumor burden according to the rotterdam criteria is the most important prognostic factor for survival in melanoma patients: A multicenter study in 388 ratients with positive sentinel nodes (Article)

2008-12-01T00:00:00Z

Summary Background Data: The more intensive sentinel node (SN) pathologic workup, the higher the SN-positivity rate. This is characterized by an increased detection of cases with minimal tumor burden (SUB-micrometastasis <0.1 mm), which represents different biology. Methods: The slides of positive SN from 3 major centers within the European Organization of Research and Treatment of Cancer (EORTC) Melanoma Group were reviewed and classified according to the Rotterdam Classification of SN Tumor Burden (<0.1 mm; 0.1-1 mm; >1 mm) maximum diameter of the largest metastasis. The predictive value for additional nodal metastases in the comple- tion lymph node dissection (CLND) and disease outcome as disease- free survival (DFS) and overall survival (OS) was calculated. Results: In 388 SN positive patients, with primary melanoma, median Breslow thickness was 4.00 mm; ulceration was present in 56%. Forty patients (10%) had metastases <0.1 mm. Additional nodal positivity was found in only 1 of 40 patients (3%). At a mean follow-up of 41 months, estimated OS at 5 years was 91% for metastasis <0.1 mm, 61% for 0.1 to 1.0 mm, and 51% for >1.0 mm (P < 0.001). SN tumor burden increased significantly with tumor thickness. When the cut-off value for SUB-micrometastases was taken at <0.2 mm (such as in breast cancer), the survival was 89%, and 10% had additional non-SN nodal positivity. Conclusion: This large multicenter dataset establishes that patients with SUB-micrometastases <0.1 mm have the same prognosis as SN negative patients and can be spared a CLND. A <0.2 mm cut-off for SUB-micrometastases does not seem correct for melanoma, as 10% additional nodal positivity is found. Copyright

Isolated Hepatic Perfusion for the Treatment of Liver Tumors: Sunset or Sunrise? (Article)

2008-10-01T00:00:00Z

Experience with isolated hepatic perfusion (IHP) is limited to a few centers in the world because of the technical difficulties, surgery-related morbidity, and unproved efficacy in randomized trials. Experimental animal IHP models have led to exploring new ways of improving efficacy, reducing technical difficulties, and minimizing regional and systemic toxicity. Future research should be directed to the identification of suitable biologic or chemotherapeutic agents, defining clinical indications, and development of technical modifications to make it more generally applicable and even repeatable.

Detection of melanoma micrometastases in sentinel nodes - the cons (Article)

2008-09-01T00:00:00Z

The sentinel node (SN) procedure in melanoma patients is important for prognostic information, but has no impact on survival. Micrometastases are identified in approximately 20% of the SNs. When a Completion Lymph Node Dissection (CLND) is performed for positive SN, additional non-SN lymph node involvement is also approximately 20%. Several classification criteria have been proposed to identify patients with SNs without a risk for additional nodes or a good prognosis. Micro anatomic analyses of metastatic SNs suggest that patients with sub-micrometastases (<0.1mm) in the SN may be judged as SN negative. Patients with this limited tumor burden in their SN have an excellent prognosis and are highly unlikely to benefit from CLND. New techniques such as ultrasound of the lymph nodal basin can be promising as an alternative for SN biopsy.

Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: A clinicopathological analysis (Article)

2008-07-01T00:00:00Z

Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. Fifteen patients with locally advanced (n≤9) and/or metastatic GIST (n≤6) were treated with imatinib followed by resection. Detailed histopathological examination was performed before and after treatment with imatinib, which was given for a median of 11 months before surgery. Ten patients showed a radiographic partial response, four patients had stable disease, and one patient progressed. At the time of surgery, the median tumor diameter was 6.5g cm. In all the nine patients with locally advanced GIST, a R0 resection could be performed. Histopathological examination showed imatinib effects in all tumors, including the case with progressive disease. All patients with locally advanced disease (n≤9) were alive after a median follow-up of 40 months (range: 18g-59), of which seven patients were free of disease. Four of the six patients treated for metastatic GIST died of disease after 30, 45, 50, and 74 months of follow-up. Remarkably, in five of six patients in whom CD117 expression was diminished or lost in the resection specimen, disease recurrence was observed. In patients with retained CD117 expression, one of the nine patients had recurrent disease. In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.

Cutaneous melanoma and sentinel lymph node biopsy (Letter To Editor)

2008-06-01T00:00:00Z

No abstract

Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients (Article)

2008-06-01T00:00:00Z

A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30 Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival.

Isolated tumor cells and long-term prognosis of patients with melanoma (Letter To Editor)

2008-05-01T00:00:00Z

When to perform surgery in stage IV melanoma patients? (Article)

2008-05-01T00:00:00Z

Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion (Article)

2008-05-01T00:00:00Z

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine. Patients and Methods: Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined. Results: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations. Conclusions: IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Sentinel lymph-node false positivity in melanoma (Letter To Editor)

2008-04-01T00:00:00Z

Somatostatin receptor in human hepatocellular carcinomas: Biological, patient and tumor characteristics (Article)

2008-04-01T00:00:00Z

Background/Aim: The evidence on the efficacy of somatostatin analogues in the treatment of hepatocellular carcinoma (HCC) in humans is conflicting. A variety of human tumors demonstrate somatostatin receptors. All subtypes bind human somatostatin with high affinity, while somatostatin analogues bind with high affinity to somatostatin receptor subtype 2 (sst2). We investigated the sst2 expression in HCC and examined whether HCCs expressing sst2 are a distinct subgroup. Patients and Methods: Forty-five human HCCs were tested for sst2 expression and biological alterations. The proliferative capacity was determined with Ki67 immunostaining and the DNA ploidy status was measured by fluorescent in situ hybridization with a chromosome 1-specific repetitive DNA probe. Expression of tumor suppressor genes (p16, p53 and Rb1) was measured by immunohistochemistry. Results: sst2 expression was detected in 30 tumors (67%). No correlation existed between sst2 expression and the immunoprofiles of the tumor suppressor genes, aneuploidy, proliferation, age, gender, α-fetoprotein levels, tumor size, tumor grade and underlying liver disease. Conclusion: In 67% of the patients with HCC, sst2 could be detected in the tumor. No clinical, pathological or biological characteristics were specific for sst2-positive tumors. Copyright

Multivariable analysis comparing outcome after sentinel node biopsy or therapeutic lymph node dissection in patients with melanoma (Article)

2007-10-01T00:00:00Z

BACKGROUND: Sentinel node (SN) status is the most important prognostic factor for overall survival in stage I or II melanoma. Yet SN-positive tumours with submicroscopic involvement of the SN (clusters of cells smaller than 0.1 mm) have shown a distant recurrence rate of only 9 per cent at 5 years, as good as that in SN-negative patients. This study compared the outcome after completion lymph node dissection (CLND) in SN-positive tumours with elective total lymph node dissection (TLND) in patients with palpable nodes. METHODS: A total of 188 patients were identified; 124 had TLND and 64 had CLND. Median follow-up was 56 and 37 months respectively. There were no significant differences between the groups regarding tumour Breslow thickness, ulceration and site of the primary tumour. Survival rates were calculated from date of primary excision. All patients with primary melanomas on extremities or trunk were included. RESULTS: On univariable analysis, the site of the primary tumour (extremity versus trunk) (P < 0.001), Breslow thickness (P = 0.005) and ulceration (P < 0.001) were prognostic for overall survival. There was a non-significant 13 per cent difference in overall survival at 5 years between CLND and TLND (P = 0.115). Excluding 15 patients who had SN disease with submicrometastases reduced the difference to 6 per cent (P = 0.415). CONCLUSION: This study showed no significant survival benefit for SN-positive CLND compared with TLND, especially when patients with nodes containing submicrometastases were excluded.

Pelvic exenteration for primary and recurrent gynaecological malignancies (Article)

2007-10-01T00:00:00Z

Objective: Analyse the outcome of pelvic exenteration for gynaecological malignancies in a tertiary referral center. Post-operative in-hospital morbidity, long-term morbidity, disease free and overall survival rates were studied. Study design: Between 1991 and 2004, 42 patients underwent an anterior, total or posterior exenteration for gynaecological malignancies. Follow-up was obtained from patient files; disease free and overall survival were calculated and prognostic factors were studied. Results: A pelvic exenteration was performed in 14 patients for primary and 28 patients for recurrent gynaecological cancers. In-hospital complications occurred in 19 patients (45%) of whom seven patients needed a reoperation (17%). Late complications occurred in 31 patients (75%); 21 reinterventions were performed (50%). Five-year disease free and overall survival was, respectively, 48 and 52%. Age, type of surgery, histology, localisation of the tumour, lateral wall involvement, completeness of resection and primary versus recurrent cancer were not identified as prognostic factors for recurrence or survival. Conclusion: Long-term survival is possible in about 50% of patients after pelvic exenteration for gynaecological cancers, but is associated with significant post-operative morbidity.

Introduction of preoperative radiotherapy in the treatment of operable rectal cancer in the Southwest region of the Netherlands (Article)

2007-09-01T00:00:00Z

Introduction: After publication of the results of the Dutch TME-trial preoperative radiotherapy followed by TME-surgery was introduced in July 2001 in the region of the comprehensive cancer centre Rotterdam as standard treatment for rectal cancer. The aim of this study is to identify the compliance to a new standardized treatment protocol i.e. the introduction of preoperative radiotherapy and to analyze the results of rectal cancer treatment in the Cancer Centre Rotterdam Region. Patients and methods: A total of 521 patients with adenocarcinoma of the rectum were included in the period from 2001 to 2003. All patients were treated with curative intent. Results: There was a significant increase of preoperative radiotherapy for patients with a tumour in the lower two-third of the rectum (21% versus 69%, p < 0.001). Peri-operative mortality rate was 2.7% and overall anastomotic leakage rate was 10.3%. There was a significant increase in the occurrence of anastomotic leakage in end-to-end anastomoses (p < 0.0001). Most anastomotic leakages occurred when patients were operated in between 4 and 8 days after the end of radiotherapy. Several aspects such as continence for urine and faeces and sexual functions were poorly registered. The total number of lymph nodes registered in pathology reports was low. The rate of reported circumferential margins increased from 37% to 70% after feedback to the regional pathology working group. Conclusion: The regional quality of rectal cancer surgery is conform preset quality-demands. There was a significant increase in the percentage preoperative radiotherapy, but still about 25% of patients who qualified for radiotherapy did not receive radiation. Pathology reports improved during registration, which illustrates the importance of registration to assess and improve quality of rectal cancer treatment.

Management of locally advanced primary and recurrent rectal cancer (Article)

2007-08-01T00:00:00Z

Treatment for patients with locally advanced and recurrent rectal cancer differs significantly from patients with rectal cancer restricted to the mesorectum. Adequate preoperative imaging of the pelvis is therefore important to identify those patients who are candidates for multimodality treatment, including preoperative chemoradiation protocols, intraoperative radiotherapy, and extended surgical resections. Much effort should be made to select patients with these advanced tumors for treatment in specialized referral centers. This has been shown to reduce morbidity and mortality and improve long-term survival rates. In this article, we review the best treatment options for patients with locally advanced and recurrent rectal cancer. We also emphasize the necessity of a multidisciplinary team, including a radiologist, radiation oncologist, urologist, surgical oncologist, plastic surgeon, and gynecologist in the diagnosis and treatment of patients with these pelvic tumors. Copyright

Prognosis of Primary Mucosal Penile Melanoma: A Series of 19 Dutch Patients and 47 Patients from the Literature (Article)

2007-07-01T00:00:00Z

Objectives: To analyze the clinical features, prognostic factors, and survival of male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra. Methods: We analyzed the clinical features, prognostic factors, and survival of 66 male patients with primary mucosal melanoma on the glans penis, meatus, fossa navicularis, and distal urethra diagnosed over the past 25 years. Data from our series of 19 patients were combined with those of 47 patients reported in the literature. Results: The overall 2 and 5-year survival rates were 63% and 31%, respectively. All patients with nodal and/or distant metastases at presentation died within 2 years. Presence of ulceration, tumor depth of 3.5 mm or more, and tumor diameter greater than 15 mm had a significantly adverse effect on prognosis. Conclusions: The prognosis of primary mucosal penile melanoma is not worse than that for cutaneous melanoma with comparable tumor thickness. Treatment should be similar to that for cutaneous melanoma, with wide radical excision and sentinel node biopsy in clinically lymph node-negative patients.

Melanoma of the anus disguised as hemorrhoids: Surgical management illustrated by a case report (Article)

2007-07-01T00:00:00Z

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer (Article)

2007-05-01T00:00:00Z

Aims: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. Methods: In the period 1994-2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. Results: Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p = 0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. Conclusion: TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Giant myositis ossificans of the leg (Article)

2007-04-01T00:00:00Z

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary (Br J Surg 2006; 93: 872-878) [8] (Article)

2007-02-01T00:00:00Z

Sentinel node biopsy for clear cell sarcoma (Article)

2006-11-01T00:00:00Z

Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.

Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? (Article)

2006-10-01T00:00:00Z

As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0); mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of <0.1 mm, 0.1-1.0 mm and >1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.

High positive sentinel node identification rate by EORTC melanoma group protocol (Article)

2006-02-01T00:00:00Z

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Schildwachtklierbiopsie bij het melanoom: prognostische betekenis en nadelen bij 300 patienten (Letter To Editor)

2005-11-01T00:00:00Z

De Vries et al. ( 2005:1845-51 ) concluderen dat de uitslag van de schildwachtklier(SWK)-procedure bij melanoompatiënten de belangrijkste prognostische factor is. Tevens concluderen zij, volgens ons ten onrechte, dat de kans op in-transitmetastasen na een SWK-procedure mogelijk toeneemt. Een aantal zeer recente publicaties van grote studies met meer dan 5000 patiënten weerlegt deze opmerking...

Isolated hypoxic hepatic perfusion with orthograde or retrograde flow in patients with irresectable liver metastases using percutaneous balloon catheter techniques: a phase I and II study. (Article)

2004-12-01T00:00:00Z

BACKGROUND: Isolated hepatic perfusion for irresectable metastases confined to the liver has reported response rates of 50% to 75%. Magnitude, costs, and nonrepeatability of the procedure are its major drawbacks. We developed a less invasive, less costly, and potentially repeatable balloon catheter-mediated isolated hypoxic hepatic perfusion (IHHP) technique. METHODS: In this phase I and II study, 18 consecutive patients with irresectable colorectal or ocular melanoma hepatic metastases were included. Two different perfusion methods were used, both with inflow via the hepatic artery, using melphalan 1 mg/kg. In the first eight patients, the portal vein was occluded, and outflow was via the hepatic veins into an intracaval double-balloon catheter. This orthograde IHHP had on average 56% leakage. In next 10 patients, we performed a retrograde outflow IHHP with a triple balloon blocking outflow into the caval vein and allowing outflow via the portal vein. The retrograde IHHP still had 35% leakage on average. RESULTS: Although local drug concentrations were high with retrograde IHHP, systemic toxicity was still moderate to severe. Partial responses were seen in 12% and stable disease in 81% of patients. The median time to local progression was 4.8 months. CONCLUSIONS: We have abandoned occlusion balloon methodology for IHHP because it failed to obtain leakage control. We are presently conducting a study using a simplified surgical retrograde IHHP method, in which leakage is fully controlled, which translates into high response rates.

One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases (Article)

2004-01-01T00:00:00Z

OBJECTIVE: The aim of this study is to describe the experience with 100 TNF-based ILP for locally advanced melanoma and to determine prognostic factors for response, time to local progression, and survival. METHODS: One hundred TNF-based ILPs were performed between 1991 and 2003 in 87 patients for whom local control by surgery of in-transit melanoma metastases was impossible. In total, 62 iliac, 33 femoral, and 5 axillary ILPs were performed in mild hyperthermic conditions with 2 to 4 mg of TNF and 10 to 13 mg of melphalan per liter of limb volume. RESULTS: Overall response was 95%, with 69% complete response, 26% partial response, and 5% no change. Complete response rate differed significantly for patients with IIIA disease versus IIIAB and IV. Local and systemic toxicity was mild to moderate in almost all cases, with no treatment-related death and one treatment-related amputation. Five-year overall survival was 32%; local progression occurred in 55% after a median of 16 months. In complete response patients, 5-year survival was 42% with local progression in 52% at a median of 22 months. Response rate and survival were significantly influenced by stage of disease; (local progression free) survival was influenced by response rate. CONCLUSIONS: TNF-based ILP results in excellent response rates in this patient population with unfavorable characteristics. Response on ILP predicts outcome in patients and reflects aggressiveness of the tumor.

Fifty tumor necrosis factor-based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors (Article)

2003-01-01T00:00:00Z

BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and melphalan is highly effective in treating limb-threatening soft tissue sarcoma (STS) and other bulky tumors. Because of fear of TNF-associated toxicity, ILP with TNF is not offered to older patients in some cancer centers, although especially in older patients, every attempt to avoid an amputation that may end their independence must be considered. METHODS: Out of 306 TNF-based ILPs, 50 ILPs were performed for limb salvage in 43 patients >75 years old (range, 75-91 years): 29 STS and 14 melanoma patients. RESULTS: In the STS patients, a response rate of 76% and a limb-salvage rate of 76% were achieved; in the melanoma patients, a 100% response rate and a 93% limb-salvage rate were achieved. Local toxicity was mild. The three postoperative deaths that occurred in the total series of 306 TNF-based ILPs in Rotterdam (<1%) occurred in patients >75 years old after leakage-free perfusions and were not related to TNF but to extremely high-risk profiles in these three patients. CONCLUSIONS: Older patients should not be withheld a TNF-based ILP for limb salvage, because the procedure is safe and highly effective in these patients.

Isolated limb perfusion for local gene delivery: efficient and targeted adenovirus-mediated gene transfer into soft tissue sarcomas (Article)

2000-01-01T00:00:00Z

OBJECTIVE: To evaluate the potential of isolated limb perfusion (ILP) for efficient and tumor-specific adenovirus-mediated gene transfer in sarcoma-bearing rats. SUMMARY BACKGROUND DATA: A major concern in adenovirus-mediated gene therapy in cancer is the transfer of genes to organs other than the tumor, especially organs with a rapid cell turnover. Adjustment of the vector delivery route might be an option creating tumor specificity in therapeutic gene expression. METHODS: Rat hind limb sarcomas (5-10 mm) were transfected with recombinant adenoviruses. Intratumoral luciferase expression after ILP was compared with systemic administration, regional infusion, or intratumoral injection using a similar dose of adenoviruses carrying the luciferase marker gene. Localization studies using lacZ as a marker gene were performed to evaluate the intratumoral distribution of transfected cells after both ILP and intratumoral injection. RESULTS: Intratumoral luciferase activity after ILP or intratumoral administration was significantly higher compared with regional infusion or systemic administration. After ILP, luciferase gene expression was minimal in extratumoral organs, whether outside or inside the isolated circuit. Localization studies demonstrated that transfection was confined to tumor cells lying along the needle track after intratumoral injection, whereas after ILP, lacZ expression was found in viable tumor cells and in the tumor-associated vasculature. CONCLUSIONS: Using ILP, efficient and tumor-specific gene transfection can be achieved. The ILP technique might be useful for the delivery of recombinant adenoviruses carrying therapeutic gene constructs to enhance tumor control.

Isolated limb perfusion as a treatment modality in cancer : from TNF to genetherapy (Doctoral Thesis)

1999-12-15T00:00:00Z