Pediatric glial tumors

Opinion statement Glial neoplasms in children comprise many heterogeneous tumors that include pilocytic and fibrillary astrocytomas, ependymomas, and the diffuse intrinsic pontine gliomas. In contrast to adults, most of whom present with high-grade fibrillary neoplasms, alternate histologies represent most cases seen in the pediatric setting. In addition, although most adult gliomas are supratentorial in location, in pediatrics infratentorial tumors (posterior fossa and brain stem) predominate. We discuss three specific tumors: diffuse intrinsic pontine gliomas; pilocytic astrocytomas; and ependymomas. Maximal surgical resection is the mainstay of therapy for both pilocytic astrocytomas and ependymomas. Failure to achieve an optimal resection often results in progression and the need for further therapy for patients with pilocytic astrocytomas, and is ultimately fatal in most children with subtotally resected ependymomas. Surgical resection has no role in the treatment of pontine gliomas. Focal radiation therapy is included routinely in the treatment of ependymomas, and it has been shown to improve event-free survival. This therapy also is used in the treatment of pontine gliomas because radiation treatment appears to slow inevitable tumor progression. Radiation therapy in pilocytic astrocytomas is generally reserved for patients who progress after an initial surgical resection or for those patients with midline tumors; these patients are poor candidates for aggressive surgical resection. The role of chemotherapy in these tumors is in evolution. Chemotherapy for pilocytic astrocytomas, particularly in young children (for whom radiation therapy is avoided), appears to be effective in the treatment of a subset of patients. Up-front chemotherapy is generally reserved for the youngest children who present with ependymoma. In the recurrence setting, chemotherapy has shown some activity, although this approach is never curative. Despite the application of various chemotherapeutics and other biologic agents, none of these therapies has improved the prognosis for patients with the uniformly lethal pontine glioma.     

Treatment of liver metastases, an update on the possibilities and results

Long-term results after liver resection for colorectal liver metastases show 5-year survival rates between 35 and 40%. However, only a limited number of patients appear to be candidates for resection, far more patients prove to have unresectable disease. Present challenges in liver surgery for colorectal metastases are to improve patient selection, to increase the resectability rate and to improve survival by multimodality treatment approaches. The variables most consistently associated with a poor prognosis and tumour recurrence are tumour-positive resection margins and the presence of extra-hepatic disease. Hence, patient selection and preoperative staging should concentrate on accurate imaging of the liver lesions and the detection of extrahepatic disease. For liver imaging, spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), supplemented by intra-operative ultrasound, are currently regarded as the best methods for evaluating the anatomy and resectability of colorectal liver metastases. Extrahepatic disease should be investigated by spiral CT of the chest and abdomen and when possible by 2-fluouro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). Resection remains the gold standard for the surgical treatment of colorectal liver metastases. In experienced centres, resection is a safe procedure and mortality rates are below 5%. The aim of resection should be to obtain tumour-negative resection margins. Edge cryosurgery should be considered in cases where very close resection margins are anticipated. The role of adjuvant chemotherapy after resection is still controversial, although two recent studies show a clear benefit. For the moment, local tumour ablative therapies such as cryotherapy and radiofrequency therapy should be considered as an adjunct to hepatic resection in those cases in which resection can not deal with all of the tumour lesions. In these cases, there seems a beneficial effect of a combined treatment consisting of resection and local tumour ablation. At this stage, there are no randomised data that local tumour ablation is as effective as resection. For a selected group of patients with unresectable liver metastases, there may be a chance to turn unresectable disease to resectable disease by aggressive neo-adjuvant chemotherapy or portal vein embolisation. For patients with unresectable disease, many different chemotherapy schedules may be used based on systemic drug administration. Regional chemotherapy and isolated liver perfusion should only be used within a study design.     

Anaplastic thyroid cancer

Anaplastic thyroid carcinoma is one of the most aggressive malignancies, with a poor prognosis. Although rare, representing only 2% of clinically recognized thyroid cancers, the overall median survival is limited to months. Most patients are elderly and seek treatment with a rapidly growing mass. Almost half the patients seek treatment with distant metastases, with as many as 75% developing distant disease during their illness. In most the patients, complete surgical resection is not possible. There are, however, a few patients with resectable disease reported in the literature who have demonstrated long-term survival with aggressive multimodal therapy that included surgery, radiation, and chemotherapy. Preclinical studies in human anaplastic thyroid carcinoma cell lines show promise that new approaches to the management of this disease will be found in the future. Until such time when an effective regimen is found, all patients with anaplastic thyroid carcinoma should be evaluated for multimodal therapy in the setting of a clinical trial.     

Chirurgische Therapie von Weichteilsarkomen der Extremitäten

Background

Surgery with curative intention in multimodal treatment concepts for patients with soft tissue sarcomas is the most important prognostic factor. Clear resection margins (R0) are one of the most important prognostic factors especially in the prevention of local recurrence and probably also in the overall survival of the disease. If R0 resection seems to be possible or can only be realized with mutilating procedures, neoadjuvant therapy concepts must be considered.

Objective

The principles of surgical therapy in patients with soft tissue sarcomas including multimodal strategies are discussed.

Material and methods

A systematic literature review of original articles and review articles over the last 15 years was performed. No prospective, randomized studies on surgery of soft tissue sarcomas were identified. The publications are discussed and assessed.

Results

In recent decades it could be shown that a compartmental resection has no significant advantages over wide resection with respect to local recurrence rate and overall survival. In the literature the rate of local recurrence is cited as being between 10?% and 40?% and the 5-year overall survival for all patients is approximately 50?%. In wide resections the ideal safety margin is not clearly defined. An R0 resection is therefore the most important criterion. A safety margin of at least 1 cm in all directions, as has been recommended for many years, can no longer be justified, the only exception being for liposarcoma (G1), the atypical lipoma of the extremities. Systemic chemotherapy (with or without hyperthermia) or radiotherapy can be beneficial and necessary in a multimodal neoadjuvant or adjuvant setting. With neoadjuvant radiotherapy a significantly increased rate of wound healing problems (>?30?%) in patients must be considered. Isolated hyperthermic limb perfusion (ILP) together with tumor necrosis factor alpha (TNF-alpha) and melphalan is an effective treatment option for patients with locally advanced soft tissue sarcomas of the extremities if an R0 resection could only be achieved by functional or anatomical amputations. Using this procedure allows resection of the soft tissue sarcoma and limb salvage in 81?% of patients. Reconstructive operative methods including flap surgery, vessel reconstruction and mesh grafts can be performed in approximately 20?% of patients.

Conclusions

A planned multidisciplinary concept from primary imaging, radiology, biopsy to histopathological investigation is necessary for defining the multimodal therapy and follow-up of patients with a soft tissue sarcoma. Surgery is still the key factor for local control and overall survival. The standard of care for soft tissue sarcomas of the extremities, with the exception of atypical lipoma, is a wide resection (R0). An ultraradical resection including vital structures for extending an already foreseeable free margin (R0) does not show any benefits. If a resection or re-resection cannot be performed in sano (i.e. R1), additional adjuvant or neoadjuvant radiotherapy should be included. The ILP procedure including TNF-alpha and melphalan is an effective treatment option in selected cases for patients with locally advanced soft tissue sarcomas of the extremities to avoid functional or anatomical amputations.     

Management of malignant mucinous adenomas

BACKGROUND: Malignant polyps are defined as adenoma with cancerous tissue penetrating into or through the muscolaris mucosae in the submucosa, and endoscopic removal is the most common treatment for such polyps. In the presence of malignant mucinous adenoma, defined as a malignant adenoma in which a significant amount of mucus is present in the stroma, the therapeutic approach is controversial and authors have performed surgical resection in all cases. The purpose of the study was to demonstrate that malignant mucinous adenoma is not a condition suggesting by itself a bowel resection. METHODS: Ten patients with malignant mucinous adenoma were enrolled in the study: endoscopic treatment alone was performed in 4 cases, and polypectomy was followed by surgical resection in 6 cases. RESULTS: At a median follow-up of 74.2 months no distant metastases had occurred in any of the patients treated with endoscopic polypectomy alone; during the follow-up, 1 patient had a local recurrence and surgical resection was performed. Only one case of residual disease was found at histology among the patients in which endoscopic polypectomy was followed by surgical resection. No complications occurred after endoscopic treatment in any case. CONCLUSIONS: In the absence of unfavorable histologic parameters, malignant mucinous adenomas should be managed with the same criteria of other malignant adenomas, and endoscopic polypectomy is considered as a safe and effective treatment when radicality criteria are fulfilled.     

Cryosurgery for locally recurrent rectal cancer.

Locally recurrent rectal cancer is, in most cases, unresectable and incurable. Palliative treatment is warranted in many cases because of the presence of severe distressing symptoms. In recurrent disease, intraluminal cryotherapy is an option for palliation. Twenty patients with local recurrence after anterior resection were treated palliatively with cryosurgery for their local symptoms. Six patients had previously had a colostomy before they were referred for palliative treatment. Thirteen patients had more than one symptom. Distant metastases were present in ten cases. The beneficial effect of cryosurgery was evident after two to three sessions. In nine patients cryotherapy achieved complete relief of local symptoms. In these patients the symptom free interval varied from 1 to 24 months (median 11 months); five patients died of disease without local symptoms. Three of these nine patients underwent a bowel diversion at a later stage because of complete stenosis. The number of treatment sessions in this group of patients varied from three to 14. The palliative index varied from 37 to 100% (mean 78%). In nine patients cryotherapy of the local recurrence gave no relief at all. Our results show that in almost half of the patients cryosurgery can palliate local complaints resulting from recurrent tumor growth after anterior resection.     

Surgical adjuvant chemotherapy in non-small cell lung cancer

In two different controlled prospective randomized trials the Lung Cancer Study Group has shown that adjuvant CAP chemotherapy is effective in prolonging the disease-free survival. These studies indicate that the adjuvant chemotherapy has its effect by way of diminishing systemic recurrences and that the adjuvant therapy is more effective in non-squamous than in squamous disease. In addition, the benefit of the treatment is more apparent in patients with more advanced, though resectable, disease. It is also becoming clear that chemotherapy either alone or in combination with radiation therapy can result in relatively high response rates in patients with disease localized to the thorax. Indeed, many of these individuals can then undergo surgical resection. It remains to be determined, however, whether or not this preoperative therapy will be effective in prolonging survival. In the future it is quite likely that optimum therapy will involve the use of preoperative treatment either with chemotherapy alone or a combination of chemotherapy and radiation therapy, followed postoperatively with adjuvant chemotherapy with a non-cross resistant regimen. In addition, a major problem is brain recurrences. Indeed the brain was the most frequent site of first recurrence systemically in many of these studies. Thus, more effective therapy directed at CNS disease will have to be developed before major breakthroughs can be anticipated in the surgical adjuvant therapy of lung cancer.     

Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic cancer cells

Pancreatic cancer is one of the most fatal types of cancer in developed countries. Most patients have locally advanced or metastatic cancerous lesions when they are diagnosed, due to the progressive, invasive and metastatic capacity of this disease to liver, lymph nodes and distant organs during early stages. Although the only curative therapy is complete surgical resection, the disease has usually already progressed by the time of diagnosis, and the majority of patients have metastatic disease. Therefore, palliative chemotherapy remains the only therapy for patients with progressive disease. Gemcitabine has been used for pancreatic cancer as the most effective anticancer drug. However, there are many cases resistant to gemcitabine. Thus, a better understanding of the molecular mechanisms of resistance to gemcitabine is essential to allow it to be used more effectively. Our previous proteomic studies demonstrated that the expression of heat-shock protein 27 (HSP27) was increased in gemcitabine-resistant pancreatic cancer cells and this might play a role in determining the sensitivity of pancreatic cancer to gemcitabine. Increased HSP27 expression in tumor specimens was related to resistance to gemcitabine and a shorter survival period in patients with pancreatic cancer. Furthermore, it has been shown that treatment strategies combining the HSP inhibitor KNK437 or interferon-γ (IFN-γ) with gemcitabine, were effective in gemcitabine-resistant pancreatic cancer cells in vitro. Furthermore, combined therapy of gemcitabine with IFN-γ of gemcitabine-resistant pancreatic cancer-bearing nude mice showed synergistic therapeutic effects on gemcitabine-resistant pancreatic cancer bearers. In this review, we summarize the current understanding of HSP27 and its role in gemcitabine resistance.     

The treatment of primary tumors of the femur with chemotherapy (if indicated), resection and reconstruction with an endoprosthesis

The treatment protocol of 15 patients with a primary tumor of the femur, including osteosarcoma, malignant fibrous histiocytoma and chondrosarcoma is presented. All patients had been selected for resection and reconstruction with an endoprosthesis. An endoprosthesis was implanted in 12 patients. The results of this type of treatment appear to be satisfactory. In eight osteosarcoma cases resection and reconstruction with an endoprosthesis combined with preoperative and postoperative chemotherapy, according to Rosen, were performed. Follow-up in all 15 patients, varying from 1.4 to 6.0 years, showed no evidence of disease in 12 patients. Three patients had died. Function of the involved leg was satisfactory in most cases. The advantage and disadvantages of the use of an endoprosthesis are discussed as well as complications in this series of patients.     

Hepatic arterial infusion therapy for pancreatic cancer

INTRODUCTION: One of the most difficult factors in curing pancreatic carcinoma is hepatic metastases. Many patients who undergo curative resection have hepatic recurrence, and unresected patients with hepatic metastases have terribly poor prognosis. AIM: In this study, we evaluated the efficacy of hepatic arterial infusion therapy for pancreatic carcinoma. PATIENTS AND METHOD: The subjects were 42 patients who underwent curative surgery, and 75 who were treated without resection over the past 10 years. A catheter was inserted from the femoral artery to the proper hepatic artery using the interventional technique. The main drug of this therapy was 5-fluorouracil. RESULT: The prophylactic therapy for curative resected cases was effective for pathologically mild venous permeation cases but not effective for severe venous permeation cases. Prophylactic hepatic arterial infusion therapy to prevent hepatic metastasis was not effective for unresected cases; however, for the patients with hepatic metastases this therapy was one of the factors for prolonging survival time.     

Targeted therapies in colorectal cancer: surgical considerations

Colorectal cancer (CRC) is a leading worldwide health concern that is responsible for thousands of deaths each year. The primary source of mortality for patients with CRC is the development and subsequent progression of metastatic disease. The most common site for distant metastatic disease is the liver. Although patients with metastatic disease to the liver have several effective treatment options, the only one for cure remains surgical resection of the liver metastases. Historically, most patients with liver metastases have had unresectable disease, and only a small percentage of patients have undergone complete curative resection. However, improved systemic therapies have led to an evolution in strategies to treat metastatic CRC to the liver. Under most conditions the management of these patients remains complex; and as chemotherapy options and new targeted therapies continue to improve outcomes, it is clear that a multidisciplinary approach must be the foundation on which advanced surgical and medical techniques are employed. Here, in this review, we highlight the role of targeted therapies in the surgical management of patients with metastatic CRC to the liver.Key Words: Colorectal cancer (CRC), metastatic colorectal cancer (mCRC), liver, targeted therapies, chemotherapy, surgical management     

Surgical treatment of colorectal cancer metastasis

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of thermal ablation. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas administration of systemic or regional chemotherapy rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens. Modern surgical treatment of colorectal liver metastases can be performed safely with low mortality and transfusion rates, and surgical treatment should be considered in patients with disease confined to their liver.     

Nonsurgical methods for liver metastases including cryotherapy,radiofrequency ablation,and infusional treatment: what's new in 2001?

Surgical resection is now well accepted as the standard treatment in 10 to 20% of patients with liver metastases. Tumor ablative techniques have been developed in recent years. The basic idea is to use them in patients with a limited number of intrahepatic deposits that are not totally resectable. Several papers published in 2001 have addressed cryotherapy. Cryotherapy can be considered an effective method for local destruction of liver metastases up to 3 to 4 cm in diameter but is also associated with a significant rate of complications. In many centers, cryoablation has now been replaced by radiofrequency ablation, the most widely used method for ablation of unresectable liver metastases. It can be performed during laparotomy, at laparoscopy, or percutaneously. Tumors less than 3 cm in their greatest diameter can be destroyed with one placement of the needle electrode. Metastases larger than 3 cm require several placements. Both cryotherapy and radiofrequency ablation are effective methods to induce necrosis of liver metastases. It is likely that in the near future, most patients with liver metastases will receive a multimodality treatment: a local treatment such as surgical resection or tumor ablation, and a general treatment such as hepatic infusional or systemic chemotherapy. Trials published in 2001 have shown that oral prodrugs of fluorouracil were probably equivalent to fluorouracil bolus administration. Regimens containing oxaliplatin or irinotecan have also been evaluated for efficacy and tolerance and by the intravenous route alone or in combination with hepatic artery infusion. Effective systemic chemotherapy regimens have resulted in increased survival rates and improved quality of life and in some cases have allowed resection of initially unresectable liver metastases.     

Interdisciplinary clinical evaluation of 58 patients with lumbar-vertebral metastases from cervico-uterine cancer

Introduction Metastases in the vertebrae of patients with cervical cancer (CeCa) can be difficult to diagnose, and the treatment is palliative in many cases. Objectives The aim of this study was to assess the time required for diagnosis, the lesion’s loco-regional extent and the therapeutic schemes applied, in a retrospective series of 58 patients with CeCa and with lumbar spinal metastases. Methods The cases were studied using an updated interdisciplinary analysis to determine the clinical and radiological variables. This study evaluated the site and extent of bone lesions and correlated these variables with instability of the spine and cord compression. Results The diagnosis of vertebrae metastases of CeCa required more than 3 months in most cases. Lumbar vertebrae L4 and L5 and specifically the vertebral body were the most-frequently affected sites. Systemic and/or extra-compartmental-extended metastases (MosV4) were observed in 44/58 patients. Radiotherapy was the only option in this group and the palliative effect achieved was minimal, or null. In 14/58 patients there was intra compartmental-extended (MosV2) and extra-compartmental limited (MosV3) single vertebral metastases and the 3 different treatment schemes were administered. In the cases treated with marginal resection of metastases, vertebroplasty plus adjuvant radiotherapy achieved significant palliative effect. Conclusions In the present series of patients, the diagnosis of metastases of the lumbar vertebrae was late, and the disease was advanced. The results obtained with radiotherapy in advanced stage disease did not improve the quality of life of patients. Metastasectomy was the therapeutic scheme in cases with intermediate stage disease and was the basis of the integrated treatment. We believe that it is necessary to shorten the diagnostic time and to apply a staging system for vertebral metastases so that appropriate individualised selection of interdisciplinary treatment would be facilitated.     

Surgical resection after gefitinib treatment in patients with lung adenocarcinoma harboring epidermal growth factor receptor gene mutation

Gefitinib is the first approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who failed to respond to conventional chemotherapy. Gefitinib has fairly effective anti-tumour activity in patients with tumours harboring EGFR gene mutations. However, there has been no data about the preoperative gefitinib treatment in NSCLC patients. We reported here two cases of surgical resection of residual disease after dramatic response to gefitinib in patients with lung adenocarcinoma harboring EGFR gene mutation. Because both of our patients initially had advanced local tumour burden (bulky N2 disease), complete resection would not have been technically feasible. However, preoperative gefitinib treatment made it possible to achieve complete resection in both patients. We believe that clinical trials are required to evaluate the role of preoperative treatment of EGFR-TKIs in patients with locally advanced NSCLC harboring EGFR gene mutation.     

The role of aggressive regional therapy for colorectal liver metastases

Surgical resection is the most effective treatment modality for liver metastases from colorectal cancer. However, most patients with liver metastases are not candidates for resection due to extensive intrahepatic disease. Approximately one-half of the patients who are able to undergo resection will eventually recur within the remnant liver. Hepatic arterial infusion (HAI) chemotherapy takes advantage of the arterial blood supply of colorectal liver metastases to increase tumor exposure to chemotherapy while minimizing systemic toxicity. HAI chemotherapy has been utilized in patients with unresectable disease in the neoadjuvant setting in an effort to convert them to resectability as well as in patients with resectable disease in the adjuvant setting in an effort to prevent recurrence. This article reviews the roles of HAI chemotherapy in an aggressive approach toward colorectal liver metastases.     

Outcome of surgical resection in Klatskin tumors

Cholangiocarcinomas are the second most frequent primary hepatic malignancy,and make up from 5% to 30% of malignant hepatic tumours.Hilar cholangiocarcinoma(HCC) is the most common type,and accounts for approximately 60% to 67% of all cholangiocarcinoma cases.There is not a staging system that permits us to compare all series and extract some conclusions to increase the long-survival rate in this dismal disease.Neither the extension of resection,according to the sort of HCC,is a closed topic.Some authors defend limited resection(mesohepatectomy with S1,S1 plus S4b-S5,local excision for papillary tumours,etc.) while others insist in the compulsoriness of an extended hepatic resection with portal vein bifurcation removed to reach cure.As there is not an ideal adjuvant therapy,R1 resection can be justified to prolong the survival rate.Morbidity and mortality rates changed along the last decade,but variability is the rule,with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%,respectively.Conclusion:Surgical resection continues to be the main treatment of HCC.Negative resection margins achieved with major hepatic resections are associated with improved outcome.Preresectional management with biliary drainage,portal vein embolization and staging laparoscopy should be considered in selected patients.Additional evidence is needed to fully define the role of orthotopic liver transplant.Portal and lymph node involvement worsen the prognosis and long-term survival,and surgery is the only option that can lengthen it.Improvements in adjuvant therapy are essential for improving long-term outcome.Furthermore,the lack of effective chemotherapy drugs and radiotherapy approaches leads us to can consider R1 resection as an option,because operated patients have a longer survival rate than those who not undergo surgery.     

A rational surgical approach to the treatment of distant melanoma metastases

The optimal treatment of melanoma involves multidisciplinary care. To many, this means surgical resection of early, localized disease and treatment of metastatic disease with chemotherapy, immunotherapy, or radiation. Because it is effective, results in little morbidity and may be repeated, surgery should have a central role in the treatment of selected patients with American Joint Committee on Cancer (AJCC) stage IV melanoma.     

Lymphadenectomy in Colorectal Cancer: Therapeutic Role and How Many Nodes Are Needed for Appropriate Staging?

Surgical resection with adequate lymphadenectomy is the treatment of choice for accurate diagnosis and proper treatment in colorectal cancer. Lymph node (LN) staging is an important prognostic factor in colorectal cancer and remains to be the most main criteria to select patients for adjuvant treatment. In colorectal cancer, a focus of treatment has been to collect as many LNs as possible to improve staging and increase survival. However, the scientific evidence for a minimum LN harvest remains controversial and the use of international cut-off values should be considered again. In practice, a thorough pursuit of a set high number of LNs may not be appropriate, but the best practice should be to collect as many LNs as possible.