Metastatic tumors to the pancreas: The role of surgery

Pancreatic metastases from other primary malignancies are a rare entity. By far, the most common primary cancer site resulting in an isolated pancreatic metastasis is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. Only few data on the surgical outcome of pancreatic resections performed for metastases from other primary tumor have been published, and there are no guidelines to address the surgical treatment for these patients. In this study, we performed a review of the published literature, focusing on the early and long-term results of surgery for the most frequent primary tumors metastasizing to the pancreas. Results for the Literature’s analysis show that in last years an increasing number of surgical resections have been performed in selected patients with limited pancreatic disease. Pancreatic resection for metastatic disease can be performed with acceptable mortality and morbidity rates. The usefulness of pancreatic resection is mainly linked to the biology of the primary tumor metastasizing to the pancreas. The benefit of metastasectomy in terms of patient survival has been observed for metastases from renal cell cancer, while for other primary tumors, such as lung and breast cancers, the role of surgery is mainly palliative.     

Pancreatic resection for metastatic tumors to the pancreas

BACKGROUND AND OBJECTIVES: The incidence of metastases to the pancreas is very low. The benefit of resection of pancreatic metastasis is poorly defined. In this review we evaluated the outcome of patients undergoing pancreatic resection for metastatic tumors to the pancreas. METHODS: Eight patients underwent pancreatic resection for metastatic tumor from December 1980 to June 2001. The primary cancer was colon carcinoma (n = 4), renal cell cancer (n = 2), duodenal leiomyosarcoma (n = 1), and malignant fibrous histiocytoma (n = 1). The median interval between primary treatment and detection of pancreatic metastases was 36 months. In two cases pancreatic metastases were synchronous with the primary tumor. RESULTS: Four patients underwent pancreatoduodenectomy, two distal pancreatectomy, one total pancreatectomy, and one median pancreatectomy. Associated resection of extrapancreatic lesions was performed in four patients, including two left hepatectomy and two left colectomy. There was no postoperative mortality, but two patients had a pancreatic and a biliary fistula, respectively. Survival averaged 23 months (range 14-42 months): four patients died for metastatic disease from 14 to 42 months after operation, while four patients are alive and well 14 to 31 months after surgery. CONCLUSIONS: Pancreatic resection for metastatic disease to the pancreas should be considered even in selected patients with limited extrapancreatic disease. Long-term survival or good palliation may be achieved.     

Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified?

BACKGROUND: To date, no consensus has been reached regarding which primary tumor subtypes are managed appropriately with hepatic metastectomy. Specifically, the role of hepatic resection for metastatic periampullary or pancreatic adenocarcinoma remains controversial. METHODS: Between 1995 and 2005, 1563 patients underwent surgical resection for periampullary carcinoma (n=608 patients) or pancreatic adenocarcinoma (head, n=905 patients; tail, n=50 patients). Data on demographics, operative details, primary tumor status, and-when indicated-extent of hepatic metastasis were collected. RESULTS: Of the 1563 patients who underwent resection of periampullary or pancreatic adenocarcinoma, 22 patients (1.4%) underwent simultaneous hepatic resection for synchronous liver metastasis. The primary tumor site was ampullary (n=1 patient ), duodenal (n=2 patients), distal bile duct (n=2 patients), or pancreas (head, n=10 patients; tail, n=7 patients). The majority of patients (86.4%) had a solitary hepatic metastasis, and the median size of the largest lesion was 0.6 cm. Hepatic metastectomy included wedge resection (n=20 patients), segmentectomy (n=1 patient), and hemihepatectomy (n=1 patient). After matching patients on primary tumor histology and location, the median survival of patients who underwent hepatic resection of synchronous metastasis was 5.9 months compared with 5.6 months for patients who underwent palliative bypass alone (P=.46) and 14.2 months for patients with no metastatic disease who underwent primary tumor resection only (P<.001). Pancreatic (median, 5.9 months) versus nonpancreatic (median, 9.9 months) primary tumor histology was not associated with a difference in survival in patients who underwent resection of synchronous liver metastasis (P=.43). CONCLUSIONS: Even in well selected patients with low-volume metastatic liver disease, simultaneous resection of periampullary or pancreatic carcinoma with synchronous liver metastases did not result in long-term survival in the overwhelming majority of patients.     

Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection]

Induction chemoradiotherapy (CRT) may downstage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a R0 resection. PATIENTS AND METHODS: We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neoadjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. RESULTS: The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The R0 resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. CONCLUSION: Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease.     

Neoadjuvant therapy for localized pancreatic cancer: guiding principles

The management of localized pancreatic cancer (PC) remains controversial. Historically, patients with localized disease have been treated with surgery followed by adjuvant therapy (surgery-first approach) under the assumption that surgical resection is necessary, even if not sufficient for cure. However, a surgery-first approach is associated with a median overall survival of only 22-24 months, suggesting that a large proportion of patients with localized PC have clinically occult metastatic disease. As a result, adjuvant therapy has been recommended for all patients with localized PC, but in actuality, it is often not received due to the high rates of perioperative complications associated with pancreatic resections. Recognizing that surgery may be necessary but usually not sufficient for cure, there has been growing interest in neoadjuvant treatment sequencing, which benefits patients with both localized and metastatic PC by ensuring the delivery of oncologic therapies which are commensurate with the stage of disease. For patients who have clinically occult metastatic disease, neoadjuvant therapy allows for the early delivery of systemic therapy and avoids the morbidity and mortality of a surgical resection which would provide no oncologic benefit. For patients with truly localized disease, neoadjuvant therapy ensures the delivery of all components of the multimodality treatment. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable (BLR) disease.     

Surgery in malignant pancreatic neuroendocrine tumors

BACKGROUND: Because of their rarity and indolent nature, optimal management of malignant pancreatic neuroendocrine tumors remains controversial. The purpose of this study is to review a series of patients with these tumors and investigate the role of surgery in the treatment. METHODS: A retrospective study of 73 patients (ages 24-86 years; 36 women) undergoing treatment at a tertiary academic medical center was performed. Patient demographics, diagnostic tests, operations, pathologic findings, adjuvant treatments, and survival were reviewed. RESULTS: Seventy-four percent of patients had advanced disease with hepatic metastases and 30% had functional tumors. Fifty-seven percent of the patients underwent pancreatic resections. Two 60-day mortalities occurred and the postoperative complication rate was 27%. Overall 5-year survival rate was 44%. There was no difference in survival between patients with functional and nonfunctional tumors. Patients undergoing resection, even in metastatic disease, had better survival than patients who had no resection (60% vs. 30%, P = 0.025). Recurrence occurred in 20% of patients who underwent a curative resection. CONCLUSION: Patients with malignant pancreatic neuroendocrine tumors commonly present with advanced disease. Although, curative resection is not frequent, survival benefit may be obtainable with aggressive surgical management even in the face of metastatic disease.     

Point de vue sur les traitements adjuvant et néoadjuvant du cancer du pancréas en 2010

About 7200 pancreatic adenocarcinomas are diagnosed every year in France. In 80% of cases, a complete surgical resection of the tumor, which is the only treatment to provide a long-term survival to the patients, is not feasible due to locoregional or metastatic spread of the disease. After a surgical resection with a curative intent, the median overall survival does not exceed 12 to 20 months due to the tumor relapse. Hence, therapeutic trials have been developed using chemotherapy or chemo/radiotherapy as adjuvant/neoadjuvant treatments combined with surgery in order to achieve better long-term survival. It is now admitted that adjuvant chemotherapy may delay tumor relapse and even increase survival in a subset of patients (10%). This has yet not been demonstrated using chemoradiotherapy. Neoadjuvant treatment with chemo/radiotherapy, especially in patients with bordeline tumour, could increase the rate of resectability in a small number of patients, margin-free surgical resections, and local control of the tumor. These approaches need to be validated prospectively. Finally, in a small number of patients with locally advanced tumors being in good condition, the treatment with chemo/radiotherapy may allow to propose a secondary resection.     

Parenchyma-sparing pancreatectomies for benign or border-line tumors of the pancreas

Standard pancreatic resections, such as pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy, result in an important loss of normal pancreatic parenchyma and may cause impairment of exocrine and endocrine function. Whilst these procedures are mandatory for malignant tumors, they seem to be too extensive for benign or border-line tumors, especially in patients with a long life expectancy. In recent years, there has been a growing interest in parenchyma-sparing pancreatic surgery with the aim of achieving better functional results without compromising oncological radicality in patients with benign, border-line or low-grade malignant tumors. Several limited resections have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor: central pancreatectomy, duodenum-preserving pancreatic head resection with or without segmental duodenectomy, inferior head resection, dorsal pancreatectomy, excavation of the pancreatic head, middle-preserving pancreatectomy, and other multiple segmental resections. All these procedures are technically feasible in experienced hands, with very low mortality, although with high morbidity rate when compared to standard procedures. Pancreatic endocrine and exocrine function is better preserved with good quality of life in most of the patients, and tumor recurrence is uncommon. Careful patient selection and expertise in pancreatic surgery are crucial to achieve the best results.     

胰腺癌患者术后化疗复发因素分析

目的探讨胰腺癌术后化疗患者的复发因素,为个体化治疗提供依据。方法分析65例胰腺癌术后化疗患者的中位复发时间、中位生存时间,以及复发与临床病理特征的关系。结果 65例患者中,23例早期复发,早期复发与肿瘤标志物CA19-9水平明显相关,而总体复发与淋巴结转移情况、病理分级关系密切,但与是否为R0切除无关。结论胰腺癌术后化疗患者的复发与淋巴结转移和病理分级密切相关,可作为患者个体化治疗的依据。     

Survival impact of pancreatic resection for metastases in the pancreas: A retrospective multi-center study

BackgroundPancreatic metastases from other primary malignancies are rare.There is no clear evidence for a treatment strategy for this condition. The purpose of this study was to assess the clinical outcomes, including prognostic factors for pancreatic resection of metastatic tumors in the pancreas, through a retrospective review.MethodsData of 35 patients who underwent pancreatic resection for pancreatic metastasis between 2005 and 2020 in eight Japanese institutions were included in this study. Survival analyses were performed using the Kaplan–Meier method, and comparisons were made using the Cox proportional hazards model.ResultsThe median follow-up period was 35 months (range, 5–102 months). Median duration from resection for primary tumor to resection for metastatic pancreatic tumor was 10.6 years (range, 0.6–29.2 years). The 3- and 5-year survival rates after resection for metastatic tumors in the pancreas were 89% and 69%, respectively. In contrast, the 3- and 5-year disease-free survival rates after resection for metastatic tumors in the pancreas were 48% and 21%, respectively. Performance status ≥1 at the time of resection for metastatic tumors in the pancreas (HR: 7.56, p = 0.036) and pancreatic metastasis tumor diameter >42 mm (HR: 6.39, p = 0.02) were significant poor prognostic factors only in the overall survival.ConclusionsThe prognosis of pancreatic resection for metastatic tumors in the pancreas is relatively good for selected patients. However, because it is prone to recurrence after radical surgery, it should only be considered in patients with good PS.     

Evaluation of the role of surgery in 25 patients with metastatic neuroblastoma

The role of surgery was evaluated using a recently proposed TNM staging system in metastatic neuroblastomas. Of twenty-five patients, twenty-four were over 1 year, 1 case was 3 months old, nine were boys, sixteen were girls, and all were stage IV using Evans-D'Angio staging system (excluding IV-s). They were retrospectively assigned a TNM clinical stage (CS) preoperatively and a pathologic stage (PS) postoperatively. All twenty-five patients were CS 4 using this TNM staging system. The role of surgery was evaluated by analyzing survival according to the postoperative PS. PS 1-2-3A were regarded as satisfactory resections, since all macroscopic tumor was removed, while PS 3B-3C-4-5 were regarded as unsatisfactory resections. With Kaplan-Meier analysis, there was a slight survival advantage when satisfactory resection of the primary tumor was achieved in the cases with any evidence of metastasis at the time of operation. However, in the cases with no evidence of metastasis at operation, there was a survival advantage when satisfactory resection of the primary tumor was done (p = 0.05). If metastatic disease is controlled prior to operation, total resection improves prognosis of metastatic neuroblastoma.     

Hepatic resection for malignant melanoma.

INTRODUCTION: Patients with metastatic melanoma have a poor prognosis with a median survival of approximately 6 months. There is a paucity of data regarding the natural history of the disease in the small subset of patients who are suitable for hepatic resection for metastatic disease confined to the liver. PATIENTS AND METHODS: Five patients were identified from a prospectively collected database of over 1000 liver resections performed in Basingstoke between 1986 and 2004. Clinical details and survival were analysed. RESULTS: Two patients died within 12 months of resection from extrahepatic disease. The other three patients are alive and disease-free at 76, 92 and 147 months, respectively. DISCUSSION: In carefully selected cases, hepatic resection for metastatic melanoma to the liver can result in long-term survival. Criteria for selection of patients as suitable for resection remain unclear.     

Isolierte Extremitätenperfusion zur lokalen Tumorkontrolle an den Gliedmaßen

Clear and wide safety margins are required in surgical resections of high-grade soft tissue sarcomas (STS) due to the proliferation patterns at the periphery of the tumors. But resections of large and deep-seated tumors are often limited by close or even marginal resection margins in order to salvage a limb and its function. Hence, neoadjuvant treatment strategies may improve subsequent surgical resection by shrinking and devitalizing the local tumor. Of these treatment modalities, hyperthermic isolated limb perfusion with TNF-α and melphalan (TM-ILP) provides the most effective deterioration of advanced and even nonresectable STS by immediate destruction of the vasculature. Different studies have reported remission rates of up to 80%, with improved subsequent resection as well as minimization of the surgical trauma usually associated with the resection of high-grade sarcomas. Obviously, TM-ILP has its greatest potential in advanced STS of the limbs with concomitant metastatic disease. Patients are ready for systemic treatment strategies within days of deterioration of the local tumor by TM-ILP. This treatment modality should be offered to these patients and should be available in tertiary cancer centers.     

Chirurgische Therapie neuroendokriner Tumoren

Neuroendocrine tumors of the pancreas, the stomach, and the duodenum belong to the “foregut” tumors. Functional (hormone-secreting) tumors can be distinguished from nonfunctional tumors. In the former case, tumors are often identified due to the hormonal symptoms they cause. In the latter case, usually symptoms due to the local tumor progression lead to the diagnosis. Surgeons need to know whether they are dealing with a sporadic or a hereditary tumor and whether malignancy is likely. In the case of solitary, small pancreatic tumors, enucleation may be sufficient, whereas large tumors require resection of the pancreatic head, segmental resection of the pancreatic corpus, or distal resections. The extent of pancreatic resection in the case of hereditary tumors is part of ongoing discussions. Endocrine tumors of the stomach may often be resected endoscopically. Otherwise, extended resections have to be based on the standards of stomach surgery. In the case of duodenal endocrine tumors, limited resections are only justified in the case of submucosal tumors. Extended resections have to follow oncological principles.     

Hepatic metastasectomy in children

BACKGROUND: There are little data regarding the safety and efficacy of hepatic metastasectomy for solid tumors in childhood. We reviewed our institutional experience to assess operative mortality and morbidity, technique of resection, local control, and survival in pediatric patients undergoing liver resection for metastases. METHODS: All pediatric patients who underwent hepatic resection for metastatic disease from August 1988 to July 2005 were retrospectively identified and clinical data were collected. RESULTS: Fifteen patients were identified during this period and primary malignancies included neuroblastoma (7), Wilms tumor (3), osteogenic sarcoma (2), malignant gastric epithelial tumor (1), and desmoplastic small round cell tumor (2). Twelve patients underwent anatomical hepatic resections and 3 had wedge resections. There were no intraoperative or postoperative deaths. The 2 postoperative complications included 1 wound infection and 1 bile collection. The median follow-up after hepatic resection was 1.6 years (0.2-7 years). Three patients remain alive. Eleven patients died of progressive disease; 4 patients suffered local recurrence. One patient died from enterocolitis and sepsis and was without evidence of malignancy at the time of death. CONCLUSIONS: Hepatic metastasectomy in children is feasible and is associated with a low operative mortality and morbidity. In this small group of patients anatomic hepatectomy was associated with better local control compared with wedge resection. Overall prognosis in these patients remains poor and the decision to perform hepatic metastasectomy should be highly selective.     

Surgery including liver resection for metastatic gastrointestinal stromal tumors or gastrointestinal leiomyosarcomas

BACKGROUND: In recent years, imatinib mesylate (STI 571), a tyrosine kinase inhibitor, has shown short-term clinical usefulness for gastrointestinal stromal tumor or gastrointestinal leiomyosarcoma (GIST). The value of surgical resection, including hepatectomy, for metastatic GIST remains unknown. Our aim was to evaluate the outcome of surgical resection, including hepatectomy, for metastatic GIST at a single institute. METHODS: Eighteen patients who underwent hepatectomy for metastatic GIST were identified and the clinicopathological data of these patients were analyzed retrospectively. RESULTS: The primary site of GIST included stomach in 10, duodenum in five, ileum in two and esophagus in one patient. A hemihepatectomy or greater resection was undertaken in eight patients. Six patients underwent simultaneous resection for primary and hepatic disease. There was no in-hospital mortality in this series. The post-hepatectomy 3- and 5-year survival rates were 63.7 and 34.0% respectively, with a median of 36 (17-227) months. Recurrence after the initial hepatectomy was documented in 17 patients (94%), and metastatic mass of the remnant liver developed in 15 of these 17 patients (88%). Three patients survived >5 years after the initial hepatectomy who underwent multiple surgical resections during this period. No clinicopathological characteristic was a significant predictive factor for survival. CONCLUSIONS: Multiple surgical resections, including hepatectomy, may contribute to important palliation in selected patients with metastatic GIST. Surgical cure seems to be difficult due to the high frequency of repeat metastasis to various sites. Therefore, adjuvant therapy must be required in the treatment of metastatic GIST.     

Pancreaticoduodenectomy for pancreatic metastatic melanoma

Isolated pancreatic metastatic melanoma is a rare occurrence. Even more rare is the surgical treatment of this lesion. However, considering the lack of effective systemic treatment and the decreasing morbidity and mortality rates of pancreatic resections in specialized centers, selected patients, especially if symptomatic, may be considered for surgical resection to achieve good palliation or improve survival. We performed a pancreaticoduodenectomy in a patient with a bleeding pancreatic metastasis from cutaneous melanoma excised 10 years before and reviewed the recent literature.     

Synchronous resection of colorectal primary and hepatic metastasis

Up to 50% of the over 140,000 new colorectal cancer patients will present with synchronous colorectal cancer and liver metastasis. Surgical management of patients with resectable synchronous colorectal hepatic metastasis is complex and must consider multiple factors, including the presence of symptoms, location of primary tumor and liver metastases, extent of tumor (both primary and metastatic), patient performance status, and underlying comorbidities. Possible approaches to this select group of patients have included a synchronous resection of the colorectal primary and the hepatic metastases or a staged resection approach. The available literature regarding the safety of synchronous versus staged approaches confirms that a simultaneous resection may be performed in selected patients with acceptable morbidity and mortality. Perioperative mortality when minor hepatectomies are combined with colorectal resection is consistently ≤5%. Perioperative morbidity varies considerably following both synchronous and staged resections. However, the bulk of the existing literature confirms that simultaneous resections are both feasible and safe when hepatic resections are limited to <3 segments. Data regarding the oncologic outcomes following synchronous versus staged resections for Stage IV colorectal cancer are more limited than those available regarding postoperative morbidity and mortality. The available data suggest equivalent overall and disease-free survival regardless of timing of resection. Experience with minimally invasive combined colorectal and hepatic resections is extremely limited to date and consists exclusively of small single center series. The potential benefits of a minimally invasive approach will await the results of larger studies.Key Words: Colorectal cancer, colorectal liver metastases, synchronous resection     

Extended resection for pancreatic adenocarcinoma

Adenocarcinoma of the pancreas presents a number of therapeutic challenges. Given the poor long-term outcomes after pancreaticoduodenectomy (PD), many surgeons have sought to improve survival via a radical or "extended" pancreatectomy which may include (a) total pancreatectomy (TP), (b) extended lymph node dissection (ELND), and (c) portal/mesenteric vascular resections. These themes of "extended" resection are addressed in this review. TP should not be performed for most cases of adenocarcinoma of the pancreatic head because of the nominal incidence of lymph node involvement along the body and tail of the pancreas, the scarcity of multicentric disease, and the better management of pancreatic leaks after PD. Most studies show no difference in long-term survival and demonstrate greater postoperative morbidity after TP than after PD. Performing ELND in addition to PD is not worthwhile because most studies do not demonstrate any long-term benefits from ELND and the circumferential dissection around the mesenteric vessels required to harvest distant lymph nodes increases postoperative morbidity. Major arterial resection increases postoperative morbidity after PD and worsens long-term survival as the need for arterial resection to achieve negative resection margins indicates more aggressive disease. In contrast, portal and/or mesenteric venous resection does not increase the morbidity after PD or impact long-term survival as venous resection is often performed because of tumor location and not extent of disease. The disappointing experience with extended resections underscores the need for better adjuvant systemic strategies and the interdisciplinary care of patients with pancreatic adenocarcinoma.     

Pancreatic resection for metastatic tumors to the pancreas

We report 3 cases of resectable pancreatic metastasis. CASE 1: A 76-year-old woman was followed after nephrectomy for renal cell carcinoma for 13 years. CT examination demonstrated a high vascular lesion in the pancreatic body and tail. We conducted distal pancreatectomy and diagnosed with metastatic tumor from renal cell carcinoma. She died of liver metastasis 8 years after pancreatic resection. CASE 2: A 64-year-old man, who had undergone right lower lobectomy for lung cancer a year ago, was found to have a mass in the pancreatic tail. We performed distal pancreatectomy and diagnosed with metastatic tumor from lung cancer. He died of lung metastasis 12 months after pancreatic resection. CASE 3: A 62- year-old woman, who had undergone left nephrectomy for renal cell carcinoma 3 years ago, was found to have a mass in the pancreatic body. With a diagnosis of metastatic pancreatic tumor from renal cell carcinoma, distal pancreatectomy was done. She died of liver and lung metastases 15 months after pancreatic resection. Long-term survival can be achieved in patients undergoing a pancreatic standard resection including lymphadenectomy for isolated metastasis from nonpancreatic sites.