Pancreatic Resection for Metastatic Melanoma. Case Report and Review of the Literature

Introduction

Pancreatic metastasis from several malignancies are increasingly encountered in clinical practice, and the usefulness of surgical resection has been suggested for certain neoplasms. Isolated pancreatic metastasis from malignant melanoma is a rare occurrence, and the role of surgery as an adjunct to systemic therapy for melanoma metastatic to a solitary or multiple sites is still debated.

Case Report

We report a patient with melanoma of unknown primary site metastatic simultaneously to the lung and pancreas 3 years after axillary lymph node dissection. Distal pancreatectomy with splenectomy and video thoracoscopic assisted resection of pulmonary metastasis were performed. The postoperative course was uneventful, but 6 months after surgery, the patient experienced single pulmonary recurrence. During chemotherapy with different drugs, pulmonary lesion remained stable for 1 year, and no abdominal recurrence occurred. After then, the size of the lesion progressively increased and a second metastasis occurred in the lung. Five months later, brain metastases occurred, and the patients died 24 months after surgery. Sixteen pancreatic resections for metastatic malignant melanoma, reported with adequate clinical details, were also retrieved from the literature.

Conclusion

In spite of the very limited experience, it appears that surgical resection is only a palliative procedure, because long-term survival is a rare event. However, considering the lack of effective systemic therapy, surgery may be considered as a part of an aggressive multidisciplinary approach in selected cases with malignant melanoma metastatic to single or multiple visceral sites.     

The role of surgery in treatment of stage IV melanoma

The prognosis for patients with melanoma has not improved over the last 30 years. So far, almost without exception, clinical trials conducted with single or multiple agent chemotherapy, biological therapy (interferon-alpha, interleukin-2), and biochemotherapy have failed to demonstrate consistent survival benefit. Without effective alternate treatments, surgery must be considered the primary treatment of melanoma, independent of disease stage. Although surgery is clearly favored as the treatment of localized melanoma, consensus opinion and clinician preference become divided once melanoma progresses beyond its primary site. Many physicians will adopt an attitude of resignation and hesitancy when treating metastatic melanoma. As a result, patients with advanced disease are often treated with medications that produce little survival or palliative benefit at the expense of significant toxicity. Numerous studies have demonstrated clear and durable survival advantages for patients undergoing complete resection of metastatic melanoma. Further, surgical resection can produce an immediate decrease in tumor burden with minimal morbidity and mortality at a reasonable cost.     

Impact of regional chemotherapy for melanoma metastases

Metastatic malignant melanoma requires sophisticated delineation of therapeutic approaches in order that palliation of the disease should be managed effectively. To date, systemic chemotherapy for melanoma metastases appears to be of only limited benefit, since tumoricidal drug levels can hardly be achieved in a way to overcome primary or secondary drug resistance of melanoma cells. With respect to topographically defined patterns of metastasis, therapeutic approaches introducing regional chemotherapy have recently promised improved palliation in the management of advanced solid tumors including melanoma. Among these approaches, isolated limb perfusion has become a well-established procedure in the treatment of melanoma which has metastasized to the extremities. The adjuvant setting of this technique is currently under investigation, and suggests a beneficial outcome in perfused high-risk patients. Intraarterial infusion techniques with or without regional venous drug hemofiltration might provide high cytotoxic tissue levels at the target region, thus subsequently leading to enhanced cell kill rates evidenced in terms of clinical responses. Angioocclusive approaches using persistent (chemoembolization) or transient (microspheres, liposomes) blocking techniques with subsequent reduction of the arterial/arteriolar blood flow may optimize the pharmacological advantage of regional drug delivery. In addition to cytoreductive surgery and systemic chemotherapy, the above-mentioned approaches of regional chemotherapy offer a new perspective in the palliative management of metastatic melanoma.     

晚期上皮性卵巢癌肠肿瘤切除的作用

目的：分析晚期上皮性卵巢癌行肿瘤细胞减灭术时肠道转移瘤行肠道肿瘤切除的临床应用。方法：回顾性分析1998～2003年52例晚期上皮性卵巢癌行肿瘤细胞减灭术时肠道转移瘤行肠道肿瘤切除的患者,与同期未行肠道肿瘤切除的仅行姑息性手术的16例患者进行比较,采用统计学方法进行处理。结果：68例手术治疗患者中,52例完成肠道肿瘤切除手术,其中34例无肉眼呵见残余肿瘤,8例残余肿瘤〈1cm,10例残余肿瘤〉1cm,其中位生存期分别为28个月、23个月和13个月,16例因肿瘤广泛转移未行肠道肿瘤切除仅行姑息性手术的患者中位生存期为7．66个月,肠道肿瘤广泛转移及肠系膜根部广泛种植是手术失败的关键。结论：晚期上皮性卵巢癌行肿瘤细胞减灭术时行肠道转移瘤切除,达到满意手术效果时对生存期提高足有帮助的,而选择恰当的患者是手术治疗的关键。     

Role of radiation therapy in the management of cutaneous malignant melanoma

Traditionally, cutaneous malignant melanoma is regarded as a radioresistant tumor. Recently, however, an increasing number of clinical studies have refuted this notion. The authors examined the role of radiation therapy in the palliative and/or adjuvant treatment of cutaneous malignant melanoma. The records of 69 patients with cutaneous malignant melanoma were reviewed. Twenty-five patients with extensive regional lymph node involvement received adjuvant radiation therapy after primary surgical treatment, and the remainder received palliative radiation therapy. The therapeutic significance of fraction size was analyzed. In the palliative radiation therapy group, the response rate was 52% with a fraction size < or = 300 cGy and 35% with a larger fraction size (p > 0.05, NS). Local regional control rates after adjuvant radiation therapy using conventional fractionation and larger fraction size were 87% and 82%, respectively (p > 0.05, NS). Radiation therapy is effective in the management of cutaneous malignant melanoma. It plays an important role in the palliation of metastatic disease and as an adjuvant treatment. No advantage in using a large fraction size over conventional dose schedules was found.     

肝脏部分切除术在复发性上皮性卵巢癌肝实质转移治疗中的价值

目的 探讨复发性上皮性卵巢癌肝实质转移患者行肝脏部分切除术的临床价值.方法 回顾性分析39例复发性上皮性卵巢癌肝实质转移患者的临床病理资料.结果 39例患者中,10例进行了肝脏部分切除术,29例仅行挽救性化疗.手术组患者的病变均为单叶,且病灶＜3个,与化疗组比较,差异有统计学意义(P＜0.05),在年龄、初次手术病理类型及病理分级、初次减瘤手术结果、初次治疗后的无瘤生存时间、肝转移瘤大小及肝转移时CA125水平等方面,差异均无统计学意义(P＞0.05).10例手术患者中,单纯行肝脏手术6例,同时行其他部位肿瘤细胞减灭术4例,其中7例减瘤手术满意.3例发生手术并发症,无手术死亡病例.8例肝脏病理切缘为阴性的患者中,局部复发6例,中位复发时间为术后12个月.减瘤手术满意的患者与行挽救性化疗的患者,肝转移后的中位总生存时间分别为26个月和9个月,肝转移后3年累积生存率分别为60.0%和16.8%,两组比较,差异有统计学意义(P＜0.05).结论 对存在肝实质转移的复发性上皮性卵巢癌患者施行包括肝脏部分切除术在内的满意肿瘤细胞减灭术,术后辅以化疗,有可能改善患者的预后.

Abstract：

Objective To investigate the validity of hepatic resection as a treatment option for hepatic parenchymal metastasis in patients with recurrent epithelial ovarian cancer. Methods A retrospective review of the clinicopathological and follow up data of 39 patients treated in our hospital from 1996 to 2008was conducted. Results Ten patients underwent partial hepatic resection for metastatic ovarian cancer.All the 10 patients underwent surgery were with unilobar metastasis and the number of tumors was lower than 3 (P ＜0.05).No significant difference existed in patient age,the primary pathology type and tumor grade,the rate of optimal primary cytoreductive surgery,the disease free survival after the primary therapy and the serum CA125 level at the liver metastasis when compared with the 29 patients accepted salvage chemotherapy(P ＞0.05).There were 7 patients who achieved optional surgery.The operation complication was 3/10 andthere was no perioperative mortality.There were 2 patients without postoperative chemotherapy in the 8 recurrent patients with microscopic negative margins.The median recurrence time was 12(5-24) months after the hepatic resection.The overall median survival periods after hepatic metastasis were 26 and 9 months and the 3-years cumulative survival rates were 60.0% and 16.8% for the optimal surgery patients including hepatic surgery and the salvage chemotherapy patients,respectively(P ＜0.05).Conclusion Hepatic resection for liver metastatic epithelial ovarian cancer is safe and may achieve long-term survival in patients after optimal second cytoreductive surgery.     

Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer

CEA is a complex glycoprotein produced by 90% of colorectal cancers and contributes to the malignant characteristics of a tumor. It can be measured in serum quantitatively, and its level in plasma can be useful as a marker of disease. Because of its lack of sensitivity in the early stages of colorectal cancer, CEA measurement is an unsuitable modality for population screening. An elevated preoperative CEA is a poor prognostic sign and correlates with reduced overall survival after surgical resection of colorectal carcinoma. A failure of the CEA to return to normal levels after surgical resection is indicative of inadequate resection of occult systemic disease. Frequent monitoring of CEA postoperatively may allow identification of patients with metastatic disease for whom surgical resection or other localized therapy might be potentially beneficial. To identify this group, serial CEA measurement appears to be more effective than clinical evaluation or any other diagnostic modality, although its sensitivity for detecting recurrent disease is not as high for locoregional or pulmonary metastases as it is for liver metastases. Several studies have shown that a small percentage of patients followed postoperatively with CEA monitoring and who undergo CEA-directed salvage surgery for metastatic disease will be alive and disease-free 5 years after surgery. Furthermore, CEA levels after salvage surgery do appear to predict survival in patients undergoing resection of liver or pulmonary metastases. However, several authors argue that CEA surveillance is not cost-effective in terms of lives saved. In support of this argument, there is no clear difference in survival after resection of metastatic disease with curative intent between patients in whom the second-look surgery was performed on the basis of elevated CEA levels and those with other laboratory or imaging abnormalities. There is also no clear consensus on the frequency or duration of CEA monitoring, although the ASCO guidelines currently recommend every 2-3 months for at least 2 years after diagnosis. In the follow-up of patients undergoing palliative therapy, the CEA level correlates well with response, and CEA is indicative of not only response but may also identify patients with stable disease for whom there is also a demonstrated benefit in survival and symptom relief with combination chemotherapy. More recently, scintigraphic imaging after administration of radiolabeled antibodies afforded an important radionuclide technique that adds clinically significant information in assessing the extent and location of disease in patients with colorectal cancer above and beyond or complementary to conventional imaging modalities. Immunotherapy based on CEA is a rapidly advancing area of clinical research demonstrating antibody and T-cell responses.     

Anorectal melanoma

Primary malignant melanoma of the anorectum is a rare and virulent malignancy associated with an extremely poor prognosis in spite of aggressive initial therapy. Fifty-one patients with this disease were treated at Memorial Sloan-Kettering Cancer Center during the last 50 years and only six (12%) survived five years. This report views in detail 36 of the patients treated since 1950. In this group there was a female predominance (21 females, 15 males), and median age was in the 6th decade (range 27-75). Common presenting symptoms were pain, bleeding, mass or "hemorrhoids" of 1-12 months duration. In two-thirds, of the cases, a radical surgical approach was attempted. Other therapy included local excision alone or combined with groin dissection, local excision followed by delayed rectal resection and local tumor destruction by cryosurgery or fulguration. Mean survival was 21.5 months. Three patients had palliative treatment only with radiation therapy. Histopathologic study of 30 lesions showed that two-thirds were bulky or polypoid lesions and two-thirds showed junctional changes. The virulent prognosis of primary anorectal melanoma appears directly related to tumor size and thickness. Although all four of the five-year survivors had radical surgery, the three whose tumors could be measured had superficial lesions. In general, curative efforts by radical surgery were no more effective than local treatment by excision or cryosurgery. One patient, however, did have a thin lesion but also had nodal metastases and survived over five years after radical surgery. Although these data suggest that radical resection may cure patients with lesions thinner than 3 mm, it does not exclude the possibility that local excision might also be curative. For larger lesions that have not been cured by radical surgery, more conservative local approaches by excision or cryotherapy might be the optimum way of achieving local palliation.     

非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择

目的 探讨有纵隔淋巴结转移（N2）的非小细胞肺癌（NSCLC）的外科治疗选择。方法 回顾性分析总结325例N2 NSCLC的外科治疗效果和经验。结果 全组5年生存率为19．6％,其中根治性切除者高于姑息性切除者,鳞癌高于腺癌,行袖式肺叶切除和全肺切除者高于常规肺叶切除者,纵隔淋巴结转移1～3枚者高于〉3枚者,术后综合治疗者高于单一外科治疗者,上述差异均有统计学意义。所有T3、T4以及M1患者均无5年生存者。结论 对于N2 NSCLC肿瘤为Tl或T2、病理类型为非腺癌以及纵隔转移淋巴结〈4枚者,外科治疗是最好的选择。对于肿瘤为T3的患者,外科治疗可能并非良策,肿瘤的根治性切除以及肺门和纵隔的系统淋巴结清扫,是病变分期和生存率提高的关键所在,术后综合治疗有助于患者的远期生存,尤其适用于有肿瘤残留和（或）纵隔转移淋巴结〉3枚的患者。     

Role of surgery in patients with stage IV melanoma

PURPOSE OF REVIEW: The purpose of this brief review is to highlight recent advances in the surgical treatment of metastatic melanoma; to review factors important in the decision-making process of selecting the most appropriate patients for resection; and to discuss the current literature in the context of site of recurrence. RECENT FINDINGS: While there are relatively few new findings on the surgical treatment of metastatic melanoma, recent reports do support prior observations in the field. The recently revised staging system for melanoma groups metastatic disease according to prognostic features. There is currently a great deal of interest in the use of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to more accurately evaluate metastatic disease. The use stereotactic radiosurgery for brain metastases has expanded recently and adds to local treatment options. When procedures are performed with palliative intent, treatment goals must be clearly defined and communicated among the patient, family and surgeon. Improved understanding of the goals of palliative surgery may be facilitated by the concept of a palliative triangle, which helps define the decision making process among the patient, family members, and surgeon. SUMMARY: Metastatic melanoma is usually associated with a dismal prognosis. When a procedure is performed with palliative intent, appropriately selected patients usually experience reliable relief of symptoms and improved quality of life. Improved survival after a complete resection with curative intent is often predicted by good performance status, longer disease-free interval, limited extent of metastatic disease, and less aggressive tumor biology.     

Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: state of the art and future developments

Peritoneal carcinomatosis (PC) had long been regarded as a terminal disease, characterized by a very poor survival and worth treating with palliative therapy. A new strategy combining maximal surgery (cytoreductive surgery, CRS), with maximal regional chemotherapy (hyperthermic intraperitoneal chemotherapy, HIPEC), has been proposed to treat PC, resulting in long-term survival rates in selected patients. The emerging trend is to view localised peritoneal carcinomatosis, in the absence of other metastases, as a regional metastatic disease that is amenable to locoregional therapy. In spite of the need for more high quality studies, many international experts now agree that the use of this new strategy is a gold standard for treating selected patients with PC with the intent of curing. The best results are achieved in patients with limited disease who have completed macroscopic tumor removal. To offer a comprehensive review, we summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcome.     

The left ventricle as the first site of uveal melanoma metastasis 13 years after treatment of the primary tumor

Treatment of patients with metastatic uveal melanoma is very challenging because the tumor commonly spreads to the liver, surgical resection of metastases is rarely possible, and there is no standard effective systemic therapy. We report the case of a 38-year-old man, who presented with metastatic involvement of the left ventricle as the first site of uveal melanoma recurrence 13 years after treatment of his primary tumor. The metastatic tumor was considered unresectable. We describe the patient's medical management over the next 3 years, the course of his disease, and the results of our review of the literature.     

Relevance of immunological parameters in progression of colorectal-carcinoma

The long-term influence on the immunological stage from surgery and/or adjuvant or palliative therapy of 23 patients with metastatic colorectal carcinoma was investigated by performing regular phenotyping and functional analysis of peripheral blood lymphocytes (PBL). The following groups were chosen: A (n=6); patients after resection of primary tumor and liver-metastases without chemotherapy. B (n=3); patients with catheter implantation after resection of primary tumor and liver metastases receiving an adjuvant arterial chemotherapy with 5-fluorouracil (5-FU) and folinic acid (5-formyltetrahydrofolic acid, FA). C (n=7); patients with non-resectable liver-metastases, receiving arterial or systemic chemotherapy after catheter implantation. D (n=7); patients with extrahepatic filiae receiving systemic palliative chemotherapy. Lymphocytes of 10 healthy volunteers served as controls. Furthermore, we were able to show effects of 5-FU and FA on the immune system.     

Palliative radiation therapy for primary gastric melanoma

Introduction

Primary gastric melanoma is an exceedingly rare cause of upper gastrointestinal bleeding (GI bleeding). Prior reports of primary gastric melanoma have mostly been treated with surgery with utilization of radiation therapy being unreported. Radiation therapy has been used to palliate bleeding of other cancers including lung, bladder, cervix, and more recently primary gastric cancers.

Case presentation

This case documents an 87-year-old male who presented with fatigue and melena, and was found to have severe anemia. Endoscopy with biopsy revealed an isolated focus of melanoma. After discharge, he presented two days later and was found to have continued bleeding. Because he was deemed a poor surgical candidate he elected to undergo palliative radiation therapy for bleeding control.

Discussion

The diagnosis of primary verses metastatic melanoma is a topic of debate. Case reports of patients with no known extra-gastric primary have undergone surgical treatment with varying outcomes. Patients with metastatic gastric melanoma have relied on chemotherapy and radiation in addition to surgery, with radiation being used in the palliative setting. The use of radiation to control bleeding in other cancers including primary gastric adenocarcinoma has been previously studied. This case documents the utilization of radiation therapy in bleeding due to primary gastric melanoma.

Conclusions

Radiation therapy can provide adequate bleeding palliation in patients with primary gastric melanoma.     

The role of external beam radiation and targeted therapy in thyroid cancer

The initial management of thyroid cancer is usually surgery, followed by radioactive iodine in differentiated thyroid cancer. The role of external beam radiotherapy for gross residual or unresected disease is discussed. For both differentiated thyroid cancer and medullary thyroid cancer, the role of external beam radiotherapy after resection of gross disease when there is a high risk of local regional failure is reviewed. In anaplastic thyroid cancers, although most patients present with unresectable disease and radiotherapy is the mainstay of treatment, the benefits of the addition of chemotherapy to radiation therapy will be discussed. Patient selection, radiation volumes, and radiation doses will be discussed. As in other tumor sites, external beam radiation has an import role in the palliative management of patient with metastatic thyroid cancer of all histologies, especially of metastases to bone but also brain and lung, but this role is not described in the review.     

Systematic review of medical treatment in melanoma: current status and future prospects

The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field. Standard treatment for patients with thick (≥2.0 mm) primary melanoma with or without regional metastases to lymph nodes is surgery followed by adjuvant therapy or clinical trial enrollment. Adjuvant therapy with interferon-α and cancer vaccines is discussed in detail. Patients who progress to stage IV metastatic melanoma have a median survival of ≤1 year. Standard treatment with chemotherapy yields low response rates, of which few are durable. Cytokine therapy with IL-2 achieves durable benefits in a greater fraction, but it is accompanied by severe toxicities that require the patient to be hospitalized for support during treatment. A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the promise of those still in clinical development that may yield incremental improvements in the treatment of advanced, metastatic melanoma.     

Does continuous-infusion interleukin-2 increase survival in metastatic melanoma?

Pharmacy logbooks and clinical trial records were used to identify all 60 patients with metastatic melanoma who were treated as inpatients with intermediate-dose, continuous-infusion interleukin-2 (IL-2) in Hoag Hospital during 1987 to 1998. The hospital tumor registry was used to identify contemporary controls who had not received inpatient IL-2, matched for having distant metastatic melanoma, and by year and stage at original diagnosis, gender, and age. The mean time from original diagnosis to the documentation of distant metastatic disease was similar in both groups, 24 to 26 months. From the date of starting IL-2 therapy, patients had a median survival of 8.8 months, 38% 1-year survival, and 20% 5-year survival, with 8 patients alive beyond 5 years. However, there was no difference in survival from the first date of distant metastatic disease (median 25.8 months for IL-2 versus 31.5 months for controls, with survival rates 5 years after metastatic disease of 26% versus 31%). There was also no difference in overall survival from the date of original diagnosis (60.1 months for the IL-2 group versus 86.3 months for controls, with 5-year survival rates of 51% versus 64%, and 10-year survival rates of 29% versus 33%). This single-institution study failed to establish a survival advantage for patients with metastatic melanoma who received intermediate-dose, continuous-infusion IL-2 administered in the inpatient setting, compared to contemporary, matched-control patients who never received inpatient IL-2 therapy. However, the 5-year survival rates after a diagnosis of distant metastatic disease were a surprisingly high 26% to 31% in both groups. In the absence of a control group, the survival impact of IL-2 has probably been overestimated from single-arm phase II and III trials.     

Melanoma in the brain: biology and therapeutic options

The development of brain metastases is a frequent occurrence in patients with disseminated melanoma and contributes to a disproportionate degree of morbidity and mortality. The prognosis is markedly reduced once a patient is diagnosed with central nervous system disease. Definitive therapeutic interventions with resection or stereotactic radiosurgery have improved outcomes and become standard approaches in the management of melanoma brain metastases. With the inclusion of whole-brain radiation in these interventions, there has been a reduction in local recurrences, but no improvement in the overall survival. Still, many patients are not candidates for surgery nor radiotherapy nor develop progressive central nervous system disease after definitive therapy. As new immune-based and targeted therapeutic agents are developed for the treatment of metastatic melanoma, understanding their activity in brain metastases is necessary for effective patient management. In this review, we discuss the biology of brain metastases in metastatic melanoma, current treatment approaches with surgery and radiotherapy, and future systemic therapeutic strategies.     

Management of brain metastases in patients with melanoma

PURPOSE OF REVIEW: Melanoma is the third most common metastatic brain tumor in the United States and is a major cause of morbidity and mortality. The development of more effective therapies for melanoma brain metastases is a major unmet clinical need and is summarized in this review. RECENT FINDINGS: Management strategies include symptomatic treatment with corticosteroids and anticonvulsants, and definitive therapy in the form of whole-brain radiation therapy, surgical resection, stereotactic radiosurgery, and systemic therapy. The data on whole-brain radiation therapy show little impact on survival, but there is evidence that it may improve neurologic deficits. Surgery may provide a survival advantage in combination with whole-brain radiation therapy in the management of a single brain melanoma metastasis, compared with whole-brain radiation therapy alone. Stereotactic radiosurgery may offer a survival advantage (in a select group of patients with limited disease) when used alone or in combination with whole-brain radiation therapy, compared with whole-brain radiation therapy alone. Fotemustine, temozolomide, and thalidomide are three agents with high central nervous system penetration that are being actively investigated as part of systemic therapy. SUMMARY: The currently available therapeutic options offer palliative relief of symptoms in most patients and a survival advantage in selected patients with melanoma and brain metastases. An urgent need exists to further define these treatments in the context of randomized trials, several of which are under way in the United States and abroad.