137 Kaohsiung J Med Sci March 2004 • Vol 20 • No 3
Received: September 12, 2003 Accepted: November 10, 2003 Address correspondence and reprint requests to: Dr. King-Teh Lee, Division of Digestive and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
E-mail: [email protected]
U
NUSUAL
U
PPER
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ASTROINTESTINAL
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LEEDING
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ATE
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ETASTASIS
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ENAL
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: A C
ASE
R
EPORT
Wen-Tsan Chang, Chee-Yin Chai,1 and King-Teh Lee
Departments of Surgery and 1Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.
Key Words: duodenal metastasis, renal cell carcinoma, upper gastrointestinal bleeding (Kaohsiung J Med Sci 2004;20:137–41)
Common metastatic sites for renal cell carcinoma (RCC) are the lungs, bone, liver, adrenal glands, and brain. Uncommon sites include the thyroid gland, gallbladder, pancreas, and orbit [1]. The gastrointestinal tract is an unusual location for solitary late recurrence of RCC [2,3]. Among solitary late metastases, duodenal metastases from RCC are uncommon and have been reported only in sporadic cases [4–7]. In addition, massive gastrointestinal tract bleeding originating from metastases is also encountered rarely, accounting for
only 0.06% of all cases of metastatic tumors in a large pan-endoscopic series [8].
Late solitary recurrence of RCC presenting with recurrent upper gastrointestinal tract bleeding is therefore very rare [9]. Although patients surviving disease-free for 8 years following nephrectomy can be considered cured [9], there have been reports of late recurrence developing 10 to 30 years after nephrectomy [2]. In this paper, we report a 63-year-old woman who underwent right nephrectomy for RCC and presented with late duodenal metastasis mani-festing as recurrent massive upper gastrointestinal bleeding 9 years later.
C
ASEP
RESENTATIONA 54-year-old woman underwent right radical nephrectomy for RCC at our hospital in 1992. The classification was
clear-or distant metastases were detected at that time and adjuvant therapy was not administered after the operation. The patient remained in good health during 9 years of follow-up.
In June 2001, at the age of 63, she suffered from an epi-sode of massive melena and marked anemia. A duodenal ulcer over the bulbar area was initially detected by endo-scopy, and blood transfusion and anti-peptic ulcer therapy was administered. Unfortunately, the patient suffered from several episodes of massive upper gastrointestinal bleeding and severe anemia. A gradually growing protruding ul-cerative mass over the posterior wall of the duodenal bulb was found at repeat endoscopy (Figure 1). Endoscopic biopsy specimens taken between August 2001 and March 2002 revealed an inflammatory polyp and necrotizing in-flammation with some dysplastic cells only. No intestinal obstruction, perforation, or intussusception had been induced by the tumor. Because of recurrent massive bleed-ing and a gradually enlargbleed-ing duodenal tumor, the patient was referred to the surgical department of our hospital in March 2002. On admission, no palpable abdominal mass or regional lymphadenopathy was detected. The patient’s hemoglobin was 5.9 g/dL and her hematocrit was 18.6%, as revealed by a complete blood count. Serum levels of the tumor markers CA19-9 and carcinoembryonic antigen (CEA) were 18.9 U/mL and 0.82 ng/mL, respectively.
Abdominal magnetic resonance imaging (MRI) showed a lobulated tumor (2.6 = 2.8 cm) in the second portion of the duodenum. There were no enlarged lymph nodes and no intra-abdominal metastases were found in the liver, pan-creas, opposite kidney, or adrenal gland. To treat the intrac-table recurrent duodenal bleeding caused by this tumor,
went laparotomy in April 2002. A grayish white tumor with an ulcerative surface and measuring 1.4 = 1.5 = 3 cm was found 1 cm distal to the pyloroduodenal junction.
Malignancy was confirmed by pathologic examination of frozen sections of ulcer biopsy. Radical subtotal gastrec-tomy was subsequently performed because Vater’s am-pulla and the pancreas were not affected. The cancer cells had infiltrated and entirely replaced the muscle layer. From comparison with specimens obtained from her right nephrectomy 9 years earlier, it was concluded that this tumor was RCC metastasis to the duodenum (Figure 2). Six regional lymph nodes showed chronic lymphadenitis but there was no apparent metastasis or invasion of other intra-abdominal organs.
The postoperative course was uneventful, except for mild episodes of paralytic ileus, and the patient was dis-charged 27 days after surgery. There was no evidence of recurrence at 10 months.
D
ISCUSSIONDuodenal metastasis from RCC is very rare [4]. Only 7.1% of gastrointestinal metastases are from RCC, and only 4% of RCC metastasizes to the small intestine [10]. In postmortem and endoscopic series, gastrointestinal tract metastases oc-cur in 0.06% to 4% of patients with malignant disease, and gastrointestinal bleeding secondary to metastases is also infrequent [8,10–12]. The most common gastrointestinal tract metastases originate from breast cancer (8.2–33%), melanoma (10–26%), lung cancer (14%), and squamous cell carcinoma of the esophagus [8]. The small intestine is in-volved in just 2% of all gastrointestinal tract metastases [10]. Furthermore, the incidence of apparently solitary metastases is only 1% to 3% among all metastases, with the duodenum being the least frequent site [6]. According to recent literature, there have been only 17 cases of duodenal metastases due to RCC reported as of 2001 [4]. However, in most of these cases, the primary and metastatic tumors were found at the same time. Therefore, late metastasis of RCC presenting as a solitary duodenal tumor with recurrent upper gastro-intestinal bleeding [2], as in this case, is very unusual.
The natural history and behavior of RCC remains unpredictable and poorly understood, in spite of intensive study. RCC may remain stable for long periods without growing and metastasizing, and metastases may develop many years after removal of the primary tumors [13–15]. This may be due to the long tumor doubling time, which
Figure 1. The ulcer became a protruding mass with partial obstruction
accounts for the delayed appearance of metastases and also permits longer survival of the host [16]. Although patients who have disease-free survival for 8 years following ne-phrectomy can be considered cured [9], as was the present case, late recurrence is seen in 5% to 11% of patients who survive 10 years from the date of nephrectomy [14,15].
The possible mechanisms of duodenal involvement of RCC may be via direct invasion by the tumor or through lymphatic, transcelomic, or hematogenous spread [6,17]. Microscopic examination of the resected specimen reveal-ed that the cancer cells had invadreveal-ed the serosa and muscu-lar layer of the duodenum, although its mucosa was not remarkable. Six regional lymph nodes revealed chronic lymphadenitis only. In the presented case, metastasis was via hematogenous spread or direct invasion.
The major complications of duodenal metastases from RCC are obstruction, intussusception, and bleeding [4–6, 12,17]. Metastatectomy can improve survival in patients with a solitary metastatic lesion and should be performed if patients are fit for surgery [2,3,6,13]. Metastatectomy can result in a 5-year survival rate of 31% to 35%, which compares favorably with the known 5-year survival of 13% to 17% in nephrectomized patients with metastatic disease [6,18]. Maldazys and deKernion concluded that a longer disease-free interval was associated with longer average survival, particularly when the interval exceeded 24 months [16]. There is no role for chemotherapy or radiotherapy in meta-static RCC [1,7], but the immunotherapeutic approach with interleukin-2 has achieved preliminary durable partial or even complete remission of advanced RCC [1]. However,
this requires further evaluation and longer follow-up. Clear-cell RCC is the most common type, accounting for about 70% of RCC, and most studies have pointed out that there is a slightly better prognosis with clear-cell RCC than with granular or mixed RCC. Sarcomatoid RCC has the worst survival rate [19].
Nevertheless, in moribund patients with multiple retroperitoneal nodes and duodenal infiltration by multiple secondaries, curative resection may be impossible and proximal diversion and palliative surgery, which is not harm-ful for critically ill patients, could offer the only effective treatment [7]. On the other hand, metastatic RCC is a hyper-vascular tumor [4,17]. In patients suffering from massive and active gastrointestinal bleeding owing to duodenal metastases from RCC, emergency arteriography and embolization of the gastroduodenal artery is an alternative life-saving treatment [17]. Lynch-Nyhan et al reported successful embolization via the gastroduodenal artery in two cases of massive gastrointestinal bleeding due to duodenal metastases of RCC [17].
Endoscopy has long been a standard diagnostic tool for upper gastrointestinal bleeding. It is also important in eva-luating metastatic lesions and obtaining biopsies, especially when radiographic findings in the gastrointestinal tract are normal [8,20]. However, in hematogenous metastasis to the gastrointestinal tract, the tumor cells fail to traverse the capillary network and implant themselves in the submucosa [8,21]. Owing to the submucosal growth, endoscopic biopsies are often inadequate [21]. It is also difficult to diagnose primary or metastatic RCC in small biopsies because of the
Figure 2. (A) Previous nephrectomy specimen, characterized by sheets of clear cells with distinct borders interspersed with numerous thin-walled
blood vessels (hematoxylin & eosin, original magnification, = 400). (B) The duodenum is infiltrated by tumor cells with clear cytoplasm and distinct cell borders. These tumor cells have the same characteristics as the primary renal cell carcinoma in (A) (hematoxylin & eosin, original magnification,
= 400).
explain why there was no histologic confirmation and clinical diagnosis until surgical exploration in the present case. The natural history of duodenal ulcer is to heal, and there is no association between carcinoma and duodenal ulcer [23,24]. It is difficult to differentiate malignant and benign ulcers at initial endoscopy [24]. However, the possibility of malignancy of the duodenal ulcer should be considered if the ulcer does not heal after 8 weeks of medical treatment or if there are polypoid masses or submucosal tumor masses with elevation and ulceration at the apex or multiple nodules of varying sizes with tip ulceration on repeated endoscopic examination [23]. An immunomarker specific for RCC is not currently available [22] and there is no universal agreement on the frequency or type of studies required in the follow-up of patients with RCC [25].
In summary, life-long follow-up is indicated in patients with RCC. In nephrectomized patients suffering from gastrointestinal bleeding, complete endoscopic evaluation is necessary. Our case emphasizes the necessity of repeat-ed endoscopic examination and histologic evaluation in suspected cancer patients. The possibility of upper gas-trointestinal bleeding due to late recurrence of RCC should be kept in mind, even though it is rare. If patients are fit for surgery, there should be no hesitation about performing surgical exploration and metastatectomy.
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