© Springer International Publishing AG 2017Emel Canbay (ed.)Unusual Cases in Peritoneal Surface Malignancies 10.1007/978-3-319-51523-6_6
6. Peritoneal Metastasis of Retroperitoneal Tumors
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Campus Virchow and Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany
KeywordsRetroperitoneal tumorPeritoneal surface malignanciesCytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Peritoneal metastases of retroperitoneal tumors are in general rare. Peritoneal metastases can arise as synchronous peritoneal seeding of the primary tumor, e.g., colorectal carcinoma or pancreas carcinoma or as a tumor recurrence after surgery affecting the peritoneum, e.g., liposarcoma or leiomyosarcoma. The mechanisms for the development of peritoneal metastases are not completely understood. Cell shedding from the primary tumor is thought to be responsible for these peritoneal deposits, which may occur spontaneously or as a result of spillage during surgical procedures.
Retroperitoneal tumors can be divided in primary retroperitoneal neoplasms and primary tumors of retroperitoneal organs.
6.2 Primary Retroperitoneal Neoplasms
Primary retroperitoneal neoplasms are an extremely rare group of tumors. Due to their location and relatively unhindered growth where symptoms develop late, the size at presentation tends to be extremely large (average size 11–20 cm).
The retroperitoneum in the abdomen is the space between the posterior parietal peritoneum anteriorly and the transversalis fascia posteriorly. It extends from the diaphragm superiorly to continue into the extraperitoneal space in the pelvis inferiorly. The retroperitoneum is loosely divided into the anterior and posterior pararenal, perirenal, and great vessel spaces. The anterior pararenal space is bordered between the posterior parietal peritoneum anteriorly, the anterior renal or Gerota fascia posteriorly, and laterally by the lateroconal fascia. This space includes the pancreaticoduodenal space and the pericolonic space. The posterior pararenal space lies between the posterior renal fascia and the transversalis fascia, whereas the perirenal space is located between the anterior and the posterior renal fascia. The great vessel space surrounds the aorta and the inferior vena cava and is anterior to the vertebral bodies and psoas muscles. The anterior and posterior pararenal spaces merge inferior to the level of the kidneys, which communicates inferiorly with the prevesical space and extraperitoneal compartments of the pelvis .
Primary retroperitoneal neoplasms are a rare but an important group of neoplasms. They account for only 0.1–0.2% of all malignancies and arise outside the retroperitoneal organs . Most primary retroperitoneal neoplasms develop from the mesodermal system. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma are responsible for more than 80% of primary retroperitoneal sarcomas. The remaining primary retroperitoneal masses arise predominantly from the nervous system .
Owing to the loose connective tissue of the retroperitoneum, these masses tend to be large (11–20 cm) at the time of presentation . They can be identified incidentally or may present clinically with a palpable abdominal or pelvic mass. Cross-sectional imaging has revolutionized the investigation of patients with retroperitoneal neoplasms. Both CT and MRI scan play an integral role in the characterization of these masses and in evaluation of their extent and involvement of adjacent structures and therefore in treatment planning.
6.3 Primary Tumors of Retroperitoneal Organs
The classification of retroperitoneal organs divides primary and secondary retroperitoneal organs due to the embryonic development. The characteristic between them is that secondary retroperitoneal organs lost their mesentery during development, while the primary retroperitoneal organs never had a mesentery.
Major primary retroperitoneal organs are:
Inferior vena cava
Major secondary retroperitoneal organs are:
Duodenum (descending and horizontal part)
Pancreas (head, neck, and body)
Most of the tumors of retroperitoneal organs are diagnosed by CT or MRI scan or by endoscopy.
6.4 Peritoneal Metastases and Treatment
6.4.1 Primary Retroperitoneal Tumors
Peritoneal metastases of primary retroperitoneal tumors are rare, and most of them occur as implant metastases described as local recurrence after surgical procedures.
Soft tissue sarcomas are rare mesenchymal tumors, accounting for 1% of all adult solid malignancies. Up to 30% of soft tissue sarcomas arise in the abdominopelvic cavity or the retroperitoneum. Retroperitoneal and both gastrointestinal and gynecological visceral sarcoma are associated with high rates of local–regional relapse after surgical resection, due to anatomical and biological features. Peritoneal sarcomatosis refers to a condition in which the intraabdominal soft tissue sarcoma spread is the dominant clinical picture. It may occur at first presentation or more often at the final stage of disease progression, especially when the primary tumor has been ruptured spontaneously or surgically [3, 4].
Peritoneal sarcomatosis has traditionally been viewed as a terminal disease with a median survival of less than 1 year, with surgery only reserved for associated complications such as intestinal obstruction and ureteral obstruction [4–6]. Bilimoria et al. found the median survival of patients with sarcomatosis treated with palliative surgery and/or chemotherapy to be 13 months with the only negative prognostic factor being tumor volume . This result is in line with other published reports describing the experience with palliation that have found the median survival to range from 7 to 15 months [5, 6].
The addition of intraperitoneal chemotherapy to cytoreductive surgery (CRS) has not been shown to improve on the results achieved with CRS alone and is therefore currently not recommended in the treatment of sarcomatosis except in well-selected patients with low tumor burden after complete cytoreduction and as part of an experimental protocol preferably in centers with expertise in peritonectomy procedures using hyperthermic intraperitoneal chemotherapy (HIPEC) as the intraperitoneal chemotherapy modality .
It is an uncommon malignant neoplasm of smooth muscle origin that tends to arise in the retroperitoneum, peripheral soft tissues, genitourinary tract, gastrointestinal tract, and large vessels and rarely in bones . About 20–67% of cases of leiomyosarcoma develop in the retroperitoneum. Complete surgical resection with wide margins reduces the rate of local recurrence; however, in retroperitoneum, it is difficult to procure wide margins all the way around the tumor due to the major vessels and other important structures . Even when complete excision is believed to have been accomplished, local recurrence rates are as high as 40–77% . Leiomyosarcomas have propensity for hematogenous spread and infrequently metastasize to lymph nodes. Distant metastases are present at the time of diagnosis in approximately 40% of cases, and most patients who survive the primary tumor will eventually develop metastases . The liver and lungs are the most common sites of metastasis in patients with leiomyosarcoma [8, 10]. Other manifestations of tumor spread include mesenteric or omental metastases, retroperitoneal lymphadenopathy, soft tissue metastases, bone metastases, splenic metastases, and ascites.
Among leiomyosarcomas of all sites, the retroperitoneal leiomyosarcomas have the worst prognosis, and about 80–87% of these patients die within 5 years . Cure of the primary tumor is difficult because of late presentation, origin within deep tissue, inability to achieve wide surgical margins, and relative insensitivity to chemotherapy and radiotherapy [8, 9]. Single or few metastatic lesions have been surgically treated in various reports [11, 12].
There is no data about the effect of CRS and HIPEC in patients suffering from leiomyosarcoma.
184.108.40.206 Malignant Fibrous Histiocytoma
Malignant fibrous histiocytoma is a typically large deep-seated tumor showing progressive, often rapid enlargement. In addition, this tumor has high propensity for metastasis to other organs, such as the lung, bone, and liver.
The treatment of malignant fibrous histiocytoma remains uncertain. Radical excision and postoperative radiotherapy are thought to control local recurrence but are limited to localized tumor . When distant metastasis is seen, surgical resection with curative intention is only possible for patients with limited pulmonary metastases who are also undergoing or have undergone complete resection of the primary tumor . Actually, however, surgical resections of metastatic tumors may improve quality of life and manage complications related to metastasis although they did not prove the survival benefit.
Peritoneal metastases from malignant fibrous histiocytoma are described in a case report, which reflects that this is an extremely rare metastatic site from a rare tumor . Treatment options in these patients have to be assessed on an individual base. Due to the fact of only one published case, CRS and HIPEC have not been described as therapeutic options for this indication.
6.4.2 Primary Tumors of Retroperitoneal Organs
Renal cell carcinoma spreads predominantly by direct extension, lymphatic dissemination, or venous invasion. Intraperitoneal metastatic spread of RCC involving mesentery and omentum is very uncommon.
To our knowledge, there are four case reports compiling six cases of peritoneal metastases of renal cell cancer [16–19].
The CT findings in three cases included extensive ascites, widespread omental infiltration, and peritoneal implants, as well as retroperitoneal metastases .
Besides the aggressive RCC subtypes with adverse histopathological features (sarcomatoid differentiation, presence of tumor necrosis, microvascular invasion and high grade), which can present with diffuse peritoneal metastases involving the omentum, also early stages of renal cell carcinoma are able to develop omental metastases after surgery .
The treatment of metastatic renal cancer is still controversial since large series of metastasectomies are reported in the literature, but little is known about the management of metastasis in atypical sites, like the peritoneum.
Surgical resection remains a critical mode of achieving control of long-term disease in metastatic RCC patients.
220.127.116.11 Adrenal Glands
Adrenocortical carcinoma is an aggressive but rare malignancy with an incidence of 0.5–2 cases per million per year [20–23]. Five-year survival rates vary from 16 to 40% and are largely dependent on the adrenocortical carcinoma stage at diagnosis .
Complete R0 resection of adrenocortical carcinoma is currently the keystone and only curative treatment modality for patients with this type of tumor. Unfortunately, ACC is a highly malignant tumor, with up to 70–85% of patients experiencing recurrence after surgical resection [25–28].
In a large national retrospective study, the best predictors of prolonged survival after first recurrence were time to first recurrence over 12 months and R0 resection. These data suggest that radical reoperation should be offered to patients with delayed recurrence . In recurrent cases, a median survival of 179 days for patients who had no therapy, 226 days for patients managed without surgery, and 1,272 days for those who had debulking surgery were demonstrated . Based on these data, patients with recurrent ACC may benefit from operative intervention, with improvement in survival and symptoms.
Mitotane monotherapy is indicated in the management of patients with metastatic disease with a low tumor burden or more indolent disease, whereas patients with aggressive disease need cytotoxic chemotherapy like mitotane plus either a combination of etoposide, doxorubicin, and cisplatin (EDP) every 4 weeks or streptozocin every 3 weeks . This therapy is now the established first-line cytotoxic therapy.
Peritoneal metastases from urothelial carcinoma of the ureter are rarely described. A recent study reported in 5 of 117 patients with upper urinary tract urothelial carcinoma initially treated with laparoscopic radical nephroureterectomy of peritoneal implants as atypic distant metastases .
Nevertheless, there is no data or recommendations about evidence-based, standardized treatment for these patients.
Rhabdomyosarcomas of the large arteries are more common in the heart and aortic arch compared to the abdominal aorta.
To our knowledge, there is only one published case report about a rhabdomyosarcoma of the abdominal aorta. The authors report an 11-year-old boy with retroperitoneal alveolar rhabdomyosarcoma at the aortoiliacal bifurcation. There is no data about peritoneal metastases of this disease so far.
18.104.22.168 Inferior Vena Cava
Primary leiomyosarcoma of the inferior vena cava is a rare neoplasia of the smooth muscle of the vein wall that accounts for approximately 0.5% of soft tissue sarcomas, with fewer than 390 cases reported in the literature [33, 34]. Surgery is the cornerstone of treatment for these tumors, but most inferior vena cava sarcomas recur even after complete resection and are associated with low disease-free survival rates [33, 35–37]. Nevertheless, good overall survival rates have previously been reported in patients treated in tertiary referral centers [33, 38].
Few publications discuss the management of recurrent inferior vena cava leiomyosarcoma. As a result, a standardized approach has not been established. Currently, surgery is the only option offered for recurrent disease if associated with minimal morbidity, even for isolated metastatic disease. The most commonly performed procedure is local excision for retroperitoneal recurrence and metastasectomy in case of lung recurrence [37, 39–44]. Adjuvant chemotherapy based on doxorubicin or a combination of doxorubicin and ifosfamide may extend the time to recurrence and increase overall survival in sarcoma patients [45, 46].
22.214.171.124 Rectum: Ascending Colon, Descending Colon
It is estimated that up to 10% of patients with colon cancer and up to 5% of patients with rectal cancer eventually develop peritoneal metastases [47, 48]. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in promising survival rates with acceptable treatment-related morbidity and mortality [49, 50]. Many retrospective studies showed median overall survival rates >36 months and 5-year survival rates between 30 and 40%. Therefore, CRS and HIPEC are currently considered to be the standard of care in selected patients with colorectal peritoneal metastases in several countries . The surgical treatment goal is complete cytoreduction in these patients. To achieve this goal, common selection criteria in many centers are the extent of peritoneal metastases which is evaluated with the peritoneal cancer index (PCI). This index was first introduced by Paul Sugarbaker in 1996 and ranges from 0 to 39. The score assesses the extent of disease by classifying the tumor size and the involvement of the parietal peritoneum and the small bowel.
126.96.36.199 Duodenum (Descending and Horizontal Part)
Primary duodenal tumors are generally rare diseases. The most common are the adenocarcinoma and the gastrointestinal stromal tumor (GIST) of the duodenum. GIST are mesenchymal tumors of the gastrointestinal tract. Duodenal GIST are 1–4% of all gastrointestinal stromal tumors . Complete surgical resection remains the best option in the treatment of GISTs, although imatinib mesylate, a tyrosine kinase inhibitor, may be effective in c-kit-positive tumors [53, 54]. About 40% of patients with primary GISTs who undergo complete resection are reported to have recurrent disease, most recurrences being local or liver metastases with a median follow-up of 24 months [55, 56]. For duodenal GISTs, the recurrence-free survival rate at 1–3 years of follow-up following resection has been reported to be 100%, 86.7%, and 95.2%, respectively [53, 56, 57]. A good prognosis is particularly seen in those who have undergone complete resection of the tumor. However, in a series from the pre-imatinib era, Miettenen et al., while reporting on the outcome in 156 patients who had surgery for duodenal GISTs, noted local recurrence, metastasis, or both in 35% of their patients .
Data about peritoneal metastases or peritoneal implants are missing. Farma et al. (2005) reported in a single center study that two patients with adenocarcinoma of the duodenum in a series of foregut malignancies with peritoneal metastases were treated with optimal cytoreduction and HIPEC with cisplatin for 90 min. The median progression-free survival of the study group was 8 months (mean, 10 months; range, 1–47 months) with a median overall survival of 8 months (mean, 18 months; range, 1–74 months). They concluded that peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease .
188.8.131.52 Pancreas (Head, Neck, and Body)
Most patients with pancreatic cancer present with distant metastasis at diagnosis. Peritoneal carcinomatosis, which is one of the most frequently encountered modes of metastasis, can cause several burdensome manifestations such as massive ascites, intestinal obstruction, and hydronephrosis . Therefore, peritoneal carcinomatosis has been regarded as a far advanced disease amenable only to palliation of symptoms because it severely impairs the quality of life of patients.
Recently, several studies reported the advancement in intervention for gastrointestinal obstruction caused by peritoneal carcinomatosis [60–62]. These palliative procedures enable to maintain performance status well and therefore promote the use of aggressive therapy even in patients with peritoneal carcinomatous . As a result, multidisciplinary treatment can be a choice of treatment in patients with several types of cancer with peritoneal carcinomatosis.
A population-based study of 2,924 pancreatic cancer patients showed that synchronous peritoneal carcinomatosis was observed in 9% of all patients, and an autopsy study reported that 22% of patients who died from pancreatic cancer had developed peritoneal carcinomatosis [64, 65].
One possible option for improving the management of peritoneal carcinomatosis might be intraperitoneal chemotherapy. It has been developed to enhance antitumor activity against peritoneal metastasis by maintaining a high concentration of the administered drug in the peritoneal cavity over a long period while sparing systemic host tissues from drug toxicity. Currently, a Japanese clinical trial comparing systemic with intraperitoneal chemotherapy is ongoing for refractory pancreatic cancer with malignant ascites .
Schneitler et al. published a case report of one patient with peritoneal carcinomatosis and liver metastases of the pancreas cancer treated with FOLFIRINOX (consisting of 5-FU/folinic acid, irinotecan, and oxaliplatin) followed by CRS and HIPEC . The follow-up of 11 months after operation proved complete oncologic remission. This therapeutic regimen might only be chosen in selected patients, while the majority of patients with peritoneal metastases of pancreatic cancer are treated with palliative chemotherapy either with FOLFIRINOX or gemcitabine monotherapy. FOLFIRONOX was reported to achieve an average life extension of 11.1 months compared to the extension of 6.8 months that was achieved using gemcitabine monotherapy .