**3. Therapeutic strategies in pancreatic metastases from various primaries**

Unfortunately, pancreatic metastases usually develop as part of the systemic recurrence and are associated with other disseminated lesions; therefore, the patient will become a candidate for palliative oncological treatment, in order, to alleviate the symptoms. In certain cases, the pancreatic lesions will develop as oligometastatic disease and by this way, the patient will become the perfect candidate for surgical treatment with curative intent. In such cases, an important benefit in terms of survival might be obtained. However, even in cases presenting metastatic lesions, surgery has been lately implemented as standard of care due to the high morbidity rates of this kind of surgical procedures. For a long period of time, it has been considered that performing a gesture of pancreatic surgery in such cases is associated with unacceptable rate of postoperative complications including the risk of pancreatic leaks or acute pancreatitis. In the last decades, improvement in hepatobiliopancreatic techniques in association with the improvement of the postoperative care lead to a successful association of such resections as part of cytoreductive surgery for various primaries [7–10]. However, the prognostic in such cases is strongly related to the origin of the pancreatic lesion.

An interesting study conducted on the subject of pancreatic resection for metastatic disease was published by Sweeney et al. in 2009. The study had as departure point a case series of three patients with pancreatic metastases from various primaries submitted to different therapeutic strategies; the first reported case was the one of a 51-year-old patient known with lobular breast cancer, 5 year earlier treated with lumpectomy, axillary node dissection and adjuvant hormonal therapy and renal cell cancer, submitted to left nephrectomy and adjuvant therapy consisting of interferon and thalidomide. The patient was further diagnosed with pulmonary metastases and was submitted to atypical lung resection and with an isolated pancreatic lesion measuring 4 × 3.1 cm at the level of the distal pancreatic tail. The pancreatic lesion was successfully resected, the histopathological studies confirming the metastatic origin from the renal cell carcinoma. However, the patient was diagnosed with disseminated liver metastases and died of disease 20 months after pancreatic surgery. The second case was the one of a 56-year-old man submitted to surgery 4 years earlier, a left pneumonectomy being performed at that moment. Four years later, he was diagnosed with an isolated lesion in the pancreatic neck, the biopsy demonstrating the metastatic origin of the lesion. He was submitted to an exploratory laparoscopy but due to the local invasion of the hepatic artery, resection was not feasible. In consequence, the patient was submitted to palliative chemotherapy and remained alive 3 years after the diagnostic of pancreatic metastases. The third case had been previously diagnosed with breast cancer for which she had been submitted to radical mastectomy followed by six cycles of chemotherapy; 5 years later, she was diagnosed with a pancreatic tumor at the junction between head and body of the pancreas, so she was submitted to a biopsy which confirmed the metastatic character of the lesion. Therefore, she was successfully submitted to surgery, an oncologic resection of the pancreatic metastasis being performed. However, the surgical procedure was followed by adjuvant chemotherapy with good long-term outcomes [11].

consist of vomiting, abdominal pain, jaundice, upper digestive hemorrhage or weight loss,

Once the diagnostic of malignant tumor of the pancreas is established, most of the times it is very difficult to distinguish between primary malignant lesions of the pancreas and metastatic ones [4]. However, patients presenting metastatic disease are usually associated with

When it comes to the most efficient imagistic study in order to determine the existence of such lesions, computed tomography seems to play an important role, most commonly such lesions being diagnosed as singular, multinodular lesions or as a diffuse infiltration with hypervascular aspect [1]. However, in up to 10% of cases, metastatic lesions of the pancreas might not be seen at standard computed tomography (CT), a positron emission tomography/computed tomography (PET-CT) is being needed. In this case, a diffuse uptake revealed by PET-CT studies might be associated with benign conditions (such as Graves' disease or autoimmune thyroiditis), while focal uptake is rather significant for the presence of a malignant lesion. In such eventualities, a percutaneous biopsy is recommended in order to have a positive diag-

the apparition of such symptoms being usually associated with poor prognostic.

**2. Imagistic studies for metastatic pancreatic lesions diagnostic**

**3. Therapeutic strategies in pancreatic metastases from various** 

prognostic in such cases is strongly related to the origin of the pancreatic lesion.

An interesting study conducted on the subject of pancreatic resection for metastatic disease was published by Sweeney et al. in 2009. The study had as departure point a case series of three patients with pancreatic metastases from various primaries submitted to different therapeutic

Unfortunately, pancreatic metastases usually develop as part of the systemic recurrence and are associated with other disseminated lesions; therefore, the patient will become a candidate for palliative oncological treatment, in order, to alleviate the symptoms. In certain cases, the pancreatic lesions will develop as oligometastatic disease and by this way, the patient will become the perfect candidate for surgical treatment with curative intent. In such cases, an important benefit in terms of survival might be obtained. However, even in cases presenting metastatic lesions, surgery has been lately implemented as standard of care due to the high morbidity rates of this kind of surgical procedures. For a long period of time, it has been considered that performing a gesture of pancreatic surgery in such cases is associated with unacceptable rate of postoperative complications including the risk of pancreatic leaks or acute pancreatitis. In the last decades, improvement in hepatobiliopancreatic techniques in association with the improvement of the postoperative care lead to a successful association of such resections as part of cytoreductive surgery for various primaries [7–10]. However, the

better outcomes when compared to pancreatic primary tumors [5].

nostic of malignancy [6].

132 Advances in Pancreatic Cancer

**primaries**

The authors went further and reviewed the literature regarding pancreatic metastases of various origins published until that moment. They reported a total number of 220 patients with this pathology with a median age of 59.2 years. Among cases which reported the symptomatology at the time of presentation, the authors underlined that up to 27.6% of cases were asymptomatic, among symptomatic cases the most commonly reported signs and symptoms are abdominal pain, upper digestive bleeding, weight loss and pancreatitis. When it comes to their localization, the most common pancreatic sites of metastases included pancreatic head (in 41.8% of cases) followed by body and tail (in 34.9% of cases), periampullary region (in 8.9% of cases) and uncinate process (in 1.1% of cases); when reported, the tumor size ranged between 1 and 11.5 cm, the average size being of 3.9 ± 2.1 cm. As the originating tumors had leaded to the apparition of pancreatic metastases, the most common primary tumor was the kidney (in 70.5% of cases) followed by the colorectal tumors (in 6.5% of cases), melanomas (in 2.7% of cases) and malignant fibrous histiocytomas (in 1.8% of cases). Among the 220 patients initially introduced in this study, surgery was performed in only 177 cases, the other 43 patients being diagnosed with unresectable lesions. The most commonly performed surgical procedures consisted of distal pancreatectomies in 25.9% of cases and pancreatoduodenectomy in 49.7% of cases, while total pancreatectomy was needed in 18.6% of cases submitted to surgery. When it comes to the short-term outcomes, the authors underlined that the reported incidence of complications was similar to the one reported in patients submitted to pancreatic resections for pancreatic primaries and consisted most often of pancreatic fistulas (in 6.5% of cases). As for the long-term outcomes, the authors calculated the median survival as well as the 2 year and 5 year survival rates only for pancreatic metastases from renal cell carcinoma (this subtype being the most frequently reported in the present study); therefore, among 177 patients submitted to surgery for pancreatic metastases from renal cell cancer, the median survival was 70 months, while the 2 year and 5 year overall survival rates were of 78 and 65%, respectively. These data suggest the potential benefit of pancreatic resections for metastatic lesions; it seems that the short-term outcomes are not significantly influenced by the metastatic character of the lesion, while the long-term outcomes seem to reveal significant longterm survival especially in oligometastatic lesions from renal primaries [11].

Another interesting conclusion of the study was the one regarding the time of diagnostic of the pancreatic lesions; in three cases pancreatic resection was performed synchronously with the resection of the primary tumor, the origin of the pancreatic metastases being represented by renal cell carcinoma, gallbladder cancer and ovarian cancer. In the remaining cases, pancreatic resection was performed for metachronous lesions; however, there was no difference in terms

Pancreatic Resections for Metastatic Disease http://dx.doi.org/10.5772/intechopen.75571 135

Renal cell carcinomas represent almost 2% of all malignant tumors in adults, being the third most common genitourinary tract cancer [13]. Although renal cell carcinoma is associated with an overall good prognostic, with 5-year survival rate of up to 95%, patients presenting distant metastases report a significant poorer outcome, with 5-year survival rates lower than 10%.

Pancreatic metastases with renal cell carcinoma origin can be diagnosed at the time of the diagnostic of the primary tumor (as synchronous lesions) or after a disease free interval (as metachronous lesions). In the second case, it seems that the prognostic is significantly influenced by the disease free survival interval, a longer period of time between the initial diagnostic and the diagnostic of metastatic lesions being associated with a lower biological aggressivity and better chances of long-term survival [14, 15]. However, it should not be omitted that pancreatic metastases from renal cell carcinoma can occur even at 10–32 years from the diagnostic of the primary tumor, so that differential diagnosis should be kept in mind any moment in which a patient known with previous history of renal cell carcinoma is diagnosed with a metachro-

Patients with pancreatic metastases from renal cell carcinomas can remain asymptomatic for a long period of time or can develop signs and symptoms such as weight loss, abdominal pain, jaundice or even pancreatitis due to the Wirsung duct obstruction caused by tumor growth; in certain cases lesions located in the pancreatic head will lead to the apparition of upper

Once a pancreatic metastasis with renal cell carcinoma origin is suspected at the imagistic studies, a fine needle biopsy might be needed in order to confirm the origin of the lesion and to decide which should be the therapeutic protocol. However, pancreatic metastases from renal cell carcinoma are the most common situation in which pancreatic resection for meta-

When it comes to the most important prognostic factors after pancreatic resections for pancreatic metastases with renal cell carcinomas, it seems that the disease free survival plays a central role; patients diagnosed with pancreatic metastases with a disease free survival longer than 2 years seem to have an improved outcome. Other factors which seem to influence the long-term outcomes are represented by the diameter of the tumor (tumors larger than 5 cm being associated with poorer outcomes), stage at the initial diagnostic and the tumoral degree

of survival between the two groups [12].

nous pancreatic tumor [16].

gastrointestinal bleeding [17, 18].

static disease has been proposed.

of differentiation [19, 20].

**4. Pancreatic metastases from renal cell carcinoma**

In a study conducted by Reddy et al. on 49 patients with metastatic pancreatic lesions, the main included primaries were renal cell carcinoma (in 21 cases), gallbladder cancer (in 6 cases), pulmonary cancer (in 4 cases), ovarian cancer (in 4 cases), sarcomas (in 4 cases), melanomas (in 3 cases), colorectal cancer (in 2 cases), breast cancer (in 1 case), hepatocellular carcinomas (in 1 case), seminomas (in 1 case), Langerhans cell histiocytosis (in 1 case) and nonpancreatic endocrine cancers (in one case). The study was conducted for a 38 year time period and reviewed data from 3830 patients submitted to pancreatic surgery; among these cases, the metastatic origin of the tumor was demonstrated in 1.6% of cases. The median age at the time of resection of pancreatic lesions was 60 years, while the most commonly encountered symptoms were abdominal pain (in 48% of cases), followed by jaundice (in 31% of cases). When it comes to the most commonly performed surgical procedures, they consisted of pancreatoduodenectomy in 31 cases, distal pancreatectomies in 14 cases and total pancreatectomy in 4 cases; among the 14 cases submitted to distal pancreatic resections, splenectomy was associated in 13 patients. When it comes to the short-term outcomes, the reported morbidity rates were 52% after pancreaticoduodenectomy, 46% after distal pancreatectomy and 25% after total pancreatectomy; however, the overall mortality rate was 0. The most often reported complications were wound infections, followed by delayed gastric emptying or pulmonary complications. When it comes to the histopathological findings, the most often reported lymph node metastases originated from renal cell carcinomas, gallbladder carcinomas, lung, colorectal carcinomas, melanomas, seminomas, sarcomas and nonpancreatic endocrine tumors, while perineural and vascular invasion were reported in gallbladder, lung, renal cell cancers and melanomas. As for the longterm outcomes, the authors reported a median overall survival rate after pancreatic resection of 3.7 years. Among long-term survivors (defined as a longer than 10 year survival after pancreatic resection), the most commonly reported origins were renal cell carcinomas, followed by Langerhans histiocytosis and seminomas. When performing an univariate analysis, the most important prognostic factors affecting the long-term survival were represented by the presence of perineural invasion and vascular invasion; surprisingly, the diameter of the metastatic tumor or lymph node metastases did not significantly influence survival. Moreover, patients who experienced any type of surgical complication as well as male patients trended to report a poorer outcome. When it comes to the influence of the cancer type on the overall prognostic, a significant influence was reported. The poorest outcomes were reported in patients submitted to surgery for pancreatic metastases originating from melanomas, followed by cases with breast cancer. No patient diagnosed with pancreatic metastases from colorectal, lung cancer or sarcoma did experience an overall survival longer than 5 years. The best outcome was reported by the patient diagnosed with metastatic Langerhans cell histiocytosis and by the patient diagnosed with seminoma, both cases being alive more than 11 years after pancreatic surgery. Another interesting conclusion of the study was the one regarding the time of diagnostic of the pancreatic lesions; in three cases pancreatic resection was performed synchronously with the resection of the primary tumor, the origin of the pancreatic metastases being represented by renal cell carcinoma, gallbladder cancer and ovarian cancer. In the remaining cases, pancreatic resection was performed for metachronous lesions; however, there was no difference in terms of survival between the two groups [12].
