Isolated limb infusion: A review

Isolated limb perfusion is the preferred treatment option for locally advanced melanoma and sarcoma confined to a limb. This treatment results in high response rates with a satisfying duration of response in both tumours. A drawback of isolated limb perfusion, however, is the invasive and complex character of the procedure. Isolated limb infusion has been designed as a minimally invasive alternative to isolated limb perfusion. Treatment results of this simple technique, reported by various centres worldwide, show comparable response rates for melanoma and sarcoma. Therefore isolated limb infusion may replace isolated limb perfusion in the future as the preferred treatment option for these locally advanced limb tumours. J. Surg. Oncol. 2009;100:169–177. © 2009 Wiley‐Liss, Inc.     

Isolated liver perfusion for non-resectable liver tumours: a review

Many treatments have been proposed for non-resectable primary or secondary hepatic cancer but the results have generally been disappointing. Isolated Hepatic Perfusion (IHP) was first attempted four decades ago but it gained acceptance only recently, after spectacular tumour responses were obtained by isolated limb perfusion with melphalan and tumour necrosis factor (TNF) for melanomas and sarcomas. Surgical isolation of the liver is a technically demanding operation that allows the safe administration of high doses of chemotherapeutics and TNF. Percutaneous techniques using balloon occlusion catheters are simpler but result in higher leakage rates from the perfusion circuit into the systemic circulation. Several phase I-II trials indicate that IHP can yield high tumour response rates, even when there is resistance to systemic chemotherapy. However, no significant advantage in overall survival has been demonstrated so far. IHP offers unique pharmacokinetic advantages for locoregional chemotherapy and biotherapy. It might also allow gene therapy with limited systemic exposure and toxicity. At present, IHP nevertheless remains an experimental treatment modality which should therefore be used in controlled trials only.     

Isolated granulocytic sarcoma: report of a case and review of the literature

Granulocytic sarcoma (GS) is an extramedullary tumor composed of granulocytic precursor cells. The tumor usually develops during the course of myelogenous leukemia or myeloproliferative disorders and may represent the initial manifestation of leukemia. Rarely, GS is recognized as an isolated tumor without any evidence of leukemia. However, in such cases, leukemia generally develops within 1 to 2 years of the diagnosis of GS. We are reporting a case of a 45-year-old woman who was diagnosed as having an isolated GS of the right breast in August 1980. She was treated with a partial mastectomy followed by 1 year of combination chemotherapy as used in the cases of acute myeloblastic leukemia and has remained free of disease to the present time. That is, she has not developed leukemia or recurrence of GS for 64 months. Based on this experience and on the review of the literature, we recommend that all cases of GS be treated with combination chemotherapy as in cases of acute myeloblastic leukemias.     

Isolated bone metastasis in testicular germ cell tumors: a case report and review of the literature

BACKGROUND: In testicular germ cell tumors (GCT), bone metastases are usually seen late in the disease progress and are almost always associated with involvement of other sites. However, isolated bone metastasis is an extremely rare finding in these patients. CASE REPORT: A 43- year-old man was admitted to the neurosurgery department of our hospital suffering from dysarthria, ataxia, headaches and a progressive swelling above the parietooccipital region of the skull. Radiological, biochemical and pathologic tests showed that the lesion of the skull was an isolated skull metastasis as an initial manifestation of nonseminomatous GCT of the testis. DISCUSSION: When a young patient presents with bone pain or painless swelling, even if it is an unusual site and isolated, testicular GCT should be considered as a differential diagnosis, as these lesions could be the first evidence of metastatic GCT.     

Isolated talus metastasis from breast carcinoma: a case report and review of the literature

BACKGROUND: Acrometastases are very rare and have been identified in only a few cases on the foot. At the onset, they might be misdiagnosed as arthritis. CASE REPORT: A 59-year-old woman with isolated metastasis to the talus, originating from breast carcinoma was treated by radiotherapy, letrazole, and intravenous bisphosphonates. RESULTS: The review of the literature revealed that this is the first case of an isolated metastasis to the bone of talus from a breast carcinoma, while there are a few cases originating from other organs. The differential diagnosis of acrometastases may be difficult. CONCLUSION: Pain in the foot or hand of a patient with a known history of malignancy should be considered as potential metastasis.     

Isolated limb perfusion of soft tissue sarcomas: A comprehensive review of literature

Patients with primary irresectable, locally advanced soft tissue sarcomas of the limbs form a challenging group for the treating physician. Multimodality treatment is necessary to guarantee optimal limb salvage and survival rates. Since the introduction of isolated limb perfusion in the late fifties, several treatment regimens have been proposed. Isolated perfusion with melphalan and TNF-α, as part of a multimodality treatment, is regarded as the current best treatment option today. Ongoing studies are investigating potential benefit of other doses, new chemotherapeutic agents and new techniques in perfusion and radiotherapy. This article provides a historical overview of published literature and insight in upcoming treatment techniques.     

双侧乳腺孤立性粒细胞肉瘤1例报告并文献复习

目的:讨论乳腺孤立性粒细胞肉瘤的临床及病理特征。方法:回顾性分析被确诊为双侧乳腺孤立性粒细胞肉瘤患者的临床资料、组织形态学、骨髓常规及免疫表型特征，并复习相关文献。结果:1例在发病前无白血病病史的62 岁女性患者体检发现双侧乳腺无痛性肿块。组织病理学可见肿瘤细胞呈列兵样排列或弥漫性分布，肿瘤细胞形态及大小一致，呈圆形或卵圆形，细胞质少，细胞核呈圆形或卵圆形，核分裂象及核仁易见，可见未成熟嗜酸性粒细胞散在分布。免疫组化提示MPO、CD45、CD34、CD68、CD117和CD43呈阳性，CD20、CD3、CD30、CD10和CKpan呈阴性。结论:双侧乳腺孤立性粒细胞肉瘤罕见。由于缺乏特异性临床特征，通常被误诊为淋巴瘤或其它良性肿瘤。肿瘤局部切除、系统化疗及放疗是其主要治疗手段。     

Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature

Fewer than 2% of patients with metastatic prostate cancer (pca) develop brain metastases. Autopsy series have confirmed the rarity of brain metastases. When present, brain metastases occur in end stage, once the pca is castrate-resistant and spread to other sites is extensive. Here, we present a rare case of a patient with pca who developed a solitary parenchymal brain metastasis as first site of relapse 9 years after radical therapy. The patient underwent craniotomy and excision of the tumour. A second recurrence was also isolated to the brain. In the literature, pca patients with brain metastases have a poor mean survival of 1–7.6 months. The patient in our case report experienced a relatively favourable outcome, surviving 19 months after his initial brain relapse.     

Inhibitory effect of 8-oxo-7,8-dihydro-2'-deoxyguanosine on the growth of KG-1 myelosarcoma in Balb/c nude mice

We previously found that 8-oxo-7,8-dihydro-2'-deoxyguanosine (oh(8)dG) kills KG-1, a human myelocytic leukemic cell line with mutational loss of 8-oxoguanine glycosylase (OGG1) activity in vitro. This observation prompted us to investigate the cytotoxicity of oh(8)dG on KG-1 in vivo. This cytotoxicity was observed by administrating oh(8)dG (3.3-330mg/kgb.w./day) for 14 days into nude mice bearing a KG-1 myelosarcoma. The results were as follows; oh(8)dG inhibited the growth of KG-1 myelosarcoma dose-dependently in terms of tumor size and weight, but had no effect on the growth of myelosarcoma of U937, a human monocytic leukemic cell line possessing wild-type OGG1. 6-Thioguanine (6-TG), an anticancer drug inhibited the growths of KG-1 and U937 tumors. 2'-Deoxyguanosine (dG) had a statistically insignificant anti-growth effect on both tumors. The oh(8)dG-treated KG-1 tumor showed the increased expression of apoptosis-processing caspases 8, 9 and 3 together with DNA fragmentation, the increased expression of cell cycle inhibitors, p16 and p27, and the decreased expression of cell cycle accelerator, cyclins and cdks, indicating the nature of cytotoxicity is cell cycle arrest and apoptosis. The genomic DNA of oh(8)dG-treated KG-1 tumors showed an increase in OGG1 sensitive sites, which is consistent with an increase in the 8-oxo-7,8-dihydroguanine (oh(8)Gua) level in the DNA of KG-1 treated with oh(8)dG in vitro. Presumably an increased level of oh(8)Gua in DNA may trigger the cytotoxicity. These findings suggest that oh(8)dG is selectively cytotoxic to KG-1 or tumors that are OGG1-deficient.     

Isolated splenic metastasis of ovarian cancer 20 years after operation: a case report and literature review

Splenic metastasis reflecting multiple metastases of cancer is often observed in the terminal stage, although solitary splenic metastasis is extremely rare. In addition, late recurrence even after 20 years of operation is very unusual. We report the case of a 52-year-old woman who was admitted to our department with a splenic tumor. She had a past history of total abdominal hysterectomy with bilateral sapingo-oophorectomy for ovarian cancer 20 years ago. Abdominal CT scan revealed a huge mass of 12 x 8 x 5.5 cm between the spleen and the left kidney. Splenectomy was performed with a diagnosis of splenic tumor. Microscopically, the tumor was a poorly differentiated adenocarcinoma including components of poorly differentiated ovarian cancer, and was diagnosed as an ovarian cancer metastasis. The patient showed no evidence of recurrence until 5 years postoperatively. Splenic metastasis is considered a terminal stage of cancer. However, when the lesion is solitary, surgical treatment is recommended.     

Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis.     

Isolated limb perfusion for melanoma patients--a review of its indications and the role of tumour necrosis factor-alpha.

AIMS: The treatment of melanoma in-transit metastases (IT-mets) can vary widely and is dependant on the size and the number of the lesions. When multiple, large lesions exist, isolated limb perfusion (ILP) has established itself as an attractive treatment option with high response rates. METHODS: Review on the various methods of treatment of melanoma in-transit metastases, with a focus on isolated limb perfusion. A Medline based literature search was performed for articles relating to this topic. Additional original papers were obtained from citations in those identified by the initial search. Indications and results are discussed and the extra value of tumour necrosis factor (TNF) is evaluated. RESULTS: ILP with Melphalan results in complete response rates of 40-82% and showed to be 54% in a large retrospective meta-analysis. The addition of TNF can improve these completes response rates (59-85%) and although no data from randomized controlled trials are available, it seems of particular value in large, bulky lesions or in patients with recurrent disease after previous ILP. CONCLUSIONS: TNF-based ILP has earned a permanent place in the treatment of patients with melanoma IT-mets. In patients with a high tumour burden, TNF-based ILP is the most efficacious procedure to obtain local control and achieve limb salvage.     

Isolated late metastasis from testicular seminoma presenting as a parotid gland mass: case report and review of the literature

Parotid metastases from non–head-and-neck cancers are rare and may represent a diagnostic and therapeutic challenge. A late metastasis to the parotid gland from a seminoma is an unusual manifestation of disease. A 45-year-old man with a history of testicular seminoma 5 years earlier presented with a rapidly progressing parotid mass. Ultrasonography and computed tomography showed a space-occupying lesion at the angle of the right jaw. The mass was infiltrating into the parotid gland and into the parapharyngeal space. A primary parotid neoplasm was suspected, and panendoscopy combined with open biopsy was performed. Histology examination confirmed a seminoma metastatic to the parotid gland, and comparison with the primary tumour showed identical histology. The patient received chemotherapy for recurrent seminoma in accordance with the pei (cisplatin, etoposide, ifosfamide) protocol. After 4 courses of chemotherapy, salvage radical parotidectomy with removal of all suspicious residual tumour tissue was performed.This case illustrates the difficulties that may be encountered in the differential diagnosis of parotid gland masses and underlines the necessity for a detailed clinical history and for strong interdisciplinary collaboration between oncologists and pathologists to correctly diagnose cases with such unusual presentations.     

Isolated limb perfusion in regional melanoma

Adjuvant perfusion to excision of a primary melanoma cannot be recommended because of its limited effect. In patients who have frequently recur-ring resectable locoregional melanoma, perfusion may provide valuable loco-regional disease control by decreasing the number of recurrences and lesions per recurrence. Randomized studies are needed to further establish the role of perfusion as an adjuvant treatment for resectable recurrences of melanoma. Unresectable limb melanoma is the primary indication for perfusion. Better response rates tend to be seen when TNF-a is used in patients who have a high tumor load. Repeat perfusion is feasible, resulting in response rates similar to those of a first perfusion for locoregional melanoma.Older age itself is not a contraindication for perfusion. The long-term health-related quality of life of survivors of melanoma who underwent treatment with perfusion is comparable to that of their healthy peers in the general Dutch population.     

Isolated limb perfusion for soft tissue sarcoma: Current practices and future directions. A survey of experts and a review of literature

Soft tissue sarcomas constitute 1% of adult malignant tumors. They are a heterogeneous group of more than 50 different histologic types. Isolated limb perfusion is an established treatment strategy for locally advanced sarcomas. Since its adoption for sarcomas in 1992, after the addition of TNFα, few modifications have been done and although indications for the procedure are essentially the same across centers, technical details vary widely. The procedures mainly involves a 60 min perfusion with melphalan and TNFα under mild hyperthermia, achieving a limb preservation rate of 72–96%; with an overall response rates from 72 to 82.5% and an acceptable toxicity according to the Wieberdink scale. The local failure rate is 27% after a median follow up of 14–31 months compared to 40% of distant recurrences after a follow up of 12–22 months. Currently there is no consensus regarding the benefit of ILP per histotype, and the value of addition of radiotherapy or systemic treatment. Further developments towards individualized treatments will provide a better understanding of the population that can derive maximum benefit of ILP with the least morbidity.     

Isolated limb perfusion with melphalan in the treatment of malignant melanoma of the extremities: a systematic review of randomised controlled trials

Isolated limb perfusion is a surgical procedure for delivering a high dose of chemotherapeutic or immunochemotherapeutic agent to a localised area, thus avoiding the severity of side-effects caused by systemic administration. This technique is generally used for treatment of patients with tumours of the limbs and extremities. We have done a systematic review of randomised controlled trials assessing the effectiveness of this treatment in patients with melanoma of the extremities. Four trials of 1038 patients met our inclusion criteria and were analysed. Although our analysis confirmed the reported increase in survival in two of the trials, neither had sufficient power to detect significant benefit for perfusion. Results from the trials showed that prophylactic perfusion has an equivocal effect on survival in patients with limb melanoma. Therefore, current evidence suggests that prophylactic isolated limb perfusion cannot be recommended as a routine adjunct to standard surgery in patients with high-risk primary limb melanoma, but only as a treatment for local disease control if other forms of locoregional therapy are not available.     

Isolated bone marrow involvement in diffuse large B cell lymphoma: a report of three cases with review of morphological, immunophenotypic and cytogenetic findings

Diffuse large B cell lymphoma (DLBL) comprises a heterogenous entity characterized by the presence of large cells, exhibiting a mature B cell phenotype. The high proliferation rate and aggressive disease remain a therapeutic challenge, but the apparent biological diversity permits a risk-stratification model for prognostic grouping through the International Prognostic Index (IPI). Empirical to this approach is the consideration of cytogenetic data, offering an insight into the pathogenetic events which may underlie neoplastic clonal evolution and disease progression. We describe three cases of DLBL presenting with isolated marrow disease, a rare primary finding in this lymphoma. All three cases showed involvement of blood and bone marrow without evidence of splenic or lymph node involvement on imaging studies. Histological and immunophenotypic findings were similar in all three cases, outlining the phenotypic maturity of this disease. Cytogenetic analysis revealed complex karyotypes in the two cases examined. M-FISH (multicolour fluorescent in situ hybridization) performed on bone marrow from case 1 showed several cryptic translocations not evident on G-banding, including a novel translocation between 2p and 9p, and an unbalanced translocation between 14q and 11q. Cytogenetic analysis in case 2 showed abnormalities involving 7q, 9p at the site of the INK4a gene, and the bcl-2 locus, findings confirmed by M-FISH. These cases serve to highlight the biological and cytogenetic heterogenity of DLBL and emphasize the need for complementary investigations in the characterization of this entity.