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[Jurnalul de Chirurgie]
ISSN: 1584-9341
Journal of Surgery
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Treatment of Bleeding Secondary to Gastric Metastases from Renal Cell Carcinoma Primary

Katherine M Guest*, George J Joy, Robin Som and Rajab Kerwat

Department of General Surgery, Queen Elizabeth Hospital, Stadium Road, London, UK

*Corresponding Author:
Katherine M Guest
Queen Elizabeth Hospital, Stadium Road
Woolwich, London, UK, SE18 4QH
Tel: +44 7454813404
Fax: +44 20 8836 4590
E-mail: [email protected]

Received Date: October 20, 2014 Accepted Date: October 24, 2015 Published Date: October 31, 2015

Citation: Guest KM, Joy GJ, Som R, Kerwat R. Treatment of Bleeding Secondary to Gastric Metastases from Renal Cell Carcinoma Primary. Journal of Surgery [Jurnalul de chirurgie]. 2015; 11(4): 153-159 DOI:10.7438/1584-9341-11-4-7

Copyright: © 2015 Guest KM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Gastric metastases from primary renal cell carcinoma (RCC) are uncommon, but not as rare as once thought. These metastases frequently present with upper gastrointestinal (UGI) bleeding. We report two such cases, and utilising lessons learnt from them, and from a literature review, propose a model of treatment for UGI bleeding secondary to metastases from RCC primaries. Both patients presented with clinically significant UGI bleeding secondary to RCC metastasis to the stomach. A literature search was conducted and a qualitative review of the published case reports and studies were undertaken. The two cases were discussed in a multi-disciplinary setting to plan management. One patient underwent gastric wedge resection; the second patient received palliative radiotherapy. Cessation of bleeding was achieved in both cases. A total of 48 cases were identified from the literature search. The reports indicate that surgery for gastric metastases has favourable outcomes in patients who do not have concurrent metastases. Palliative radiotherapy in this setting has not previously been described. A model of how these patients could be managed was subsequently constructed; the key question to answer is how disseminated the disease is. Treatment modalities are still debated and should be discussed on a case-by-case basis. However, the literature suggests that surgical intervention has good therapeutic and prognostic benefit in patients with isolated metastatic disease to the stomach. For those with widespread metastases, there are several management options available. We advise that radiotherapy should also be considered as an option in the management of patients with bleeding lesions and concurrent metastatic disease.

Keywords

Renal cell carcinoma; Metastasis; Stomach; Gastrointestinal bleeding

Introduction

Gastric metastases from primary renal cell carcinoma (RCC) are considered rare. However, there are nearly 50 cases described in the literature. We present two cases of patients presenting with clinically significant bleeding from gastric RCC metastasis; utilising lessons learnt from these cases, and from a literature review, we propose a model of treatment for gastrointestinal (GI) bleeding secondary to metastases from RCC.

Case 1

A 68-year-old Caucasian lady (Ms DA) was referred to the emergency department (ED) by her general practitioner following a collapse. She complained of fatigue, anorexia and weight loss of around 1.5 stone over 6 months. Blood tests revealed a microcytic anaemia (haemoglobin = 51 grams/litre, mean corpuscular volume (MCV) = 71 femtolitres).

Past medical history was significant for left-sided clear cell renal cell carcinoma 21 years prior to this presentation, for which she underwent a nephrectomy. Her drug history included levothyroxine, aspirin and prochlorperazine. Ms DA lived with her partner, was a non-smoker and consumed no alcohol. Physical examination at the time of presentation did not reveal anything of note.

Initial treatment involved resuscitation and transfusion of 3 units of packed red cells and an infusion of vitamin B complex. Her haemoglobin levels returned to normal parameters following this.

A computerised tomography (CT) scan showed an elevated soft tissue lesion arising from the posterior wall of the central stomach with no evidence of metastatic disease.

Ms DA subsequently underwent a gastroscopy which showed 2 ulcerated, sessile polyps, the largest measuring 20 millimetres, and a submucosal polyp on the greater curvature of the stomach. All lesions were biopsied. A colonoscopy was attempted but was limited by melaena.

A positron emission tomography CT scan and a nuclear medicine bone scan were performed, neither of which showed metastatic disease.

Histological examination of the biopsies showed clear cell RCC metastasis. Her case was discussed at a multi-disciplinary meeting (MDM), where it was decided that a laparoscopic gastric wedge resection would be most appropriate for her. This procedure was performed successfully without post-operative complications.

Histology of the resected specimen showed a well circumscribed 15 millimetre nodule in the submucosa with ulceration into the mucosa, no spread into stomach muscle and clear surgical margins.

Since this, Ms DA has annual surveillance gastroscopies which have not shown any evidence of recurrence (Figure 1).

surgery-nodular-gastric-metastasis

Figure 1: Ms DA – nodular gastric metastasis with mucosal ulceration.

Case 2

A 73-year-old Asian lady (Mrs HB) presented to the ED with a one day history of per rectal bleeding, including both fresh blood and melaena. There were no associated symptoms and examination was unremarkable.

Serological investigations confirmed a microcytic anaemia, with haemoglobin = 82 grams/litre, and MCV = 77.3 femtolitres. She had already been receiving iron supplementation for this.

In 2005, she underwent left-sided nephrectomy for clear cell RCC. Surveillance CT scan that year had shown nodules in the nephrectomy bed as well as pulmonary spread. She received Sunitinib for this.

During her admission she required repeated transfusions of packed red cells for continuous per rectal bleeding and persistent anaemia.

A gastroscopy showed a distal gastric lesion in the greater curvature of the stomach with ulcerated overlying mucosa and clot. Biopsies of the lesion were taken which confirmed clear cell RCC metastasis.

Mrs HB’s case was discussed in a MDM, where it was felt surgical intervention would not be appropriate given the presence of multiple metastases. Palliative radiotherapy was thought to be the best course of treatment in view of her ongoing bleeding. Thus, she underwent a repeat gastroscopy to reassess the lesion and endoscopically place marking clips for focused palliative radiotherapy. Cessation of bleeding was successfully achieved (Figure 2).

surgery-bleeding-mass

Figure 2: Mrs HB – bleeding mass with overlying mucosal ulceration in the greater curvature of the stomach.

Literature Review

Renal cell carcinomas account for nearly 2% of cancers worldwide and are associated with high rates of metastases, with these often occurring several months after curative treatment [1,2]. Metastases originating from RCCs are most commonly found in the lungs, brain, breast and bones and are of clear cell histology [3-8].

Method

A review of the current literature on metastatic renal cell carcinoma to the stomach was performed using PubMed. The search terms were: “renal cell carcinoma stomach” + “renal cell carcinoma metastasis stomach”. A total of 48 cases were identified (Table I).

Table I: Case Reports of Gastric Metastases in RCC.

Paper Year Age (years) Sex Presenting Complaint Interval Post-Nephrectomy (years) Location Number of lesions Type of Lesion Treatment Other Metastases Survival outcomes Ref.
Sullivan et al. 1980 69 M Melaena 7.5 Antrum Single Polypoid Antrectomy None - [17]
Bisesti et al. 1984 64 M Chest pain 14 Antrum Single Ulcer Subtotal Gx None - [18]
Nakamura et al. 1984 65 M Melaena 9 - - - Partial Gx Ileum Died 33 days post-op [19]
Ibáñez Olcoz et al. 1989 60 F Melaena 1.8 Body Multiple Polypoid None Lung, brain - [20]
Márquez et al. 1992 70 M Melaena 0.1 Body Single Ulcer None Lung Died after 4 weeks [21]
Durous et al. 1992 66 M Anaemia 12 Fundus Multiple - Interferon Lung, parotid - [22]
Otowa et al. 1992 61 F Haematemesis 0 Body Multiple - Total Gx None Died 3 months post-op [23]
Herrera Puerto et al. 1993 63 M Haematemesis 0.1 Antrum Single Ulcer None None Died 4 weeks post nephrectomy [24]
Boruchowicz et al. 1995 48 M Dysphagia 1.3 Fundus Single Polypoid Chemotherapy Lung, liver, oesophagus - [25]
Blake et al. 1995 63 M Haematemesis 6 - Single Tumour Palliative embolization Lung Alive after 5 months [26]
Odori et al. 1998 59 M Asymptomatic 4.4 Body Single Ulcer Total Gx None No tumour recurrence at 17 months [27]
Picchio et al. 2000 50 F Melaena 14 Body Single Polypoid Subtotal Gx None No tumour recurrence at 6 months [28]
Mascarenhas et al. 2001 66 M Haematemesis 7 Body Single Ulcer Partial Gx Lung, pleura Died after 36 months [29]
Suárez-Ortega et al. 2004 70 F Melaena 0 - Multiple Polypoid Palliative Lung - [30]
Kobayashi et al. 2004 78 M Anaemia 6.2 Body Single Not stated Gx (NOS) None Died after 5 months [31]
Kok et al. 2004 60 M Melaena 20 Body Multiple Tumour - - - [32]
Suárez Fonseca et al. 2004 61 F Melaena 4 Body Single Polypoid Palliative Lung - [33]
Lamb et al. 2005 69 F Haematemesis 3 Body Single Tumour Palliative embolization (x6) Lung Died after 23 months [34]
Portanova et al. 2006 67 F Melaena 5 Body Single Polypoid Total Gx Pancreas Alive after 2 weeks [35]
Hollerbach et al. 2006 56 M Anaemia - Body Multiple Polypoid Endoscopic mucosal resection None - [36]
Riviello et al. 2006 68 M Melaena 11 Fundus Single Polypoid Total Gx, chemotherapy Lung, spleen, pancreas, liver, lymph nodes Died after 2 years [37]
Saidi et al. 2007 - - Melaena 10 Body Single Polypoid Wedge Rx None Disease free after 18 months [38]
Pezzoli et al. 2007 78 M Anaemia 5 Body Multiple Polypoid Electrosurgical snare resection - Died after 6 months [3]
Haffner et al. 2007 80 M Anaemia 0 Fundus Multiple Ulcer Endoscopic ablation Lung Alive after 5 months [39]
Ko et al. 2008 71 M Abdominal mass - Body Multiple Tumour - Lung - [40]
Roh et al. 2008 60 F Dyspepsia 8 Body Multiple Polypoid Subtotal Gx None - [41]
Pollheimer et al. 2008 69 M Abdominal pain 4.2 Body Single Ulcer Tamoxifen Lung, bone, adrenal Died after 19 months [5]
Pollheimer et al. 2008 77 M Asymptomatic 6.3 Antrum Single Ulcer Interferon Lung, bone Died after 4 months [5]
Pollheimer et al. 2008 83 F Melaena 1.7 Antrum Multiple - Endoscopic ablation, Interferon Lung, liver, pancreas Died after 5 months [5]
Pollheimer et al. 2008 65 F Haematemesis&Melaena 13.1 - Multiple - Endoscopic ablation Lung, brain Died after 3 months [5]
Pollheimer et al. 2008 69 M Abdominal pain 9.3 Body Multiple - Endoscopic ablation, Sunitinib Lung, bone Alive after 2 years [5]
Maeda et al. 2009 49 M Anaemia 1.7 Body Single Polypoid Partial Gx - - [42]
Kibria et al. 2009 53 M Melaena 0 Fundus Single Polypoid None Lung, bone Died after 2 months [8]
Yamamoto et al. 2009 74 M Melaena 5 Body Single Polypoid Wedge Rx Brain Died 1 month post-op [4]
Sugasawa et al. 2010 69 M Melaena 19 Fundus Single Ulcer Wedge Rx None Disease free after 12 months [43]
Tiwari et al. 2010 58 F Haematemesis&Melaena 0 Antrum Single Polypoid Subtotal Gx Lung Died 2 months post-op [7]
Palade et al. 2011 - - Melaena 8 - Single Ulcer Partial Gx Lung, brain, bone - [44]
Cruz et al. 2011 56 F Melaena 6 Antrum Single Tumour Subtotal Gx Lung, brain - [45]
Eslick et al. 2011 65 M PR Bleeding 9 Body Single Ulcer Endoscopic polypectomy None Alive after 6 years [2]
Rodrigues et al. 2012 45 F Haematemesis 9 Body Single Ulcer Sunitinib Lung, ovary Died after 4 months [46]
Namikawa et al. 2012 65 M Mass on CT 23 Body Single Polypoid Wedge Rx None Disease free after 2 months [9]
Gómez-de-la-Cuesta et al. 2012 87 F Melaena 4 Body Multiple Polypoid Palliative Lung, pancreas - [10]
Siriwardana et al. 2012 71 M Anaemia 3 - Single Polypoid Endoscopic mucosal resection None Disease free after 15 months [47]
Kim et al. 2012 79 M Abdominal pain 0 Body Single Ulcer Endoscopic submucosal dissection None Disease free after 6 months [6]
Thoufeeq et al. 2012 59 F Dyspepsia 3 Fundus Single Polypoid Sunitinib Brain - [48]
Onorati et al. 2013 80 - - 20 - - - - - - [49]
Sakurai et al. 2014 61 M Melaena 2 Body Single Polypoid Partial Gx Lung, bone, brain Died 4 months post-op [50]
Ikari et al. 2014 64 M - 22 - Single Tumour Endoscopic submucosal dissection None Disease free after 30 months [51]

Demographics and clinical characteristics

The majority of patients were male (67%) with a mean age of 67 years (range 45-83 years). The mean interval post-nephrectomy was 6.9 years. This implies a significant delay in the development of gastric metastases following curative treatment. Melaena was the most frequently reported presenting complaint (46%).

Tumour characteristics

Clear cell histology was evident in all cases which reported a histopathological diagnosis. Over two thirds of patients had single lesions with the appearance of polyps, ulcers or tumours. The majority of lesions were located in the body of the stomach (63%).

Concurrent metastatic disease was found in 28 patients, the majority of which was present in the lung (86%), followed by metastases to the brain (25%), and bone (21%).

Management and outcomes

Surgical intervention was used in 20 of the 48 cases identified, half of which had no other concurrent metastatic disease. Four patients underwent total gastrectomy. The remainder had partial gastrectomies including 5 subtotal gastrectomies, 4 wedge resections and 1 antrectomy. Six cases did not specify the type of surgery. Three of the cases reporting use of wedge resections were performed for treatment of lesions <7 centimetres located in the gastric body.

Of those patients who did not receive surgery, 10 had endoscopic therapy, either in the form of polypectomy, ablation or mucosal resection. Palliative embolization was the treatment of choice in 2 cases, both requiring multiple embolizations in order to achieve haemostasis. Lamb et al. (2005) report a case of a patient who required 6 embolizations following 10 upper GI bleeds. Eight patients received chemotherapy and 7 did not receive any treatment. There were no case reports in the literature which described the use of palliative radiotherapy.

Cessation of bleeding was achieved in all patients who underwent surgical or endoscopic treatment for bleeding lesions (Figure 3).

surgery-Gastric-Metastases

Figure 3: Treatment Modalities for Management of Gastric Metastases in RCC (n = 44).

Survival

Survival rates are generally poor with metastatic RCC, with most patients dying a few months after diagnosis [1,2]. In those with metastases to other organs in addition to the stomach, outcomes were worse (range 4 weeks to 36 months survival) than in those with isolated gastric metastases (range 4 weeks survival to alive after 6 years). Nearly half of the cases with widespread metastatic disease did not survive beyond 6 months, although several papers did not report survival data.

Of the 10 patients who received surgical intervention for isolated gastric metastases, 5 were cancer-free after 2-18 months. As only 7 cases in this category had published survival statistics, it is evident that surgical intervention carries symptomatic benefit in these patients, as well as the potential for curative treatment.

Overall survival for patients with RCC metastases to the stomach ranged from 4 weeks to alive after 6 years.

Discussion

Gastric metastases from RCC are rare and usually present with significant upper gastrointestinal haemorrhage.

Establishing the histopathological differentiation between metastatic disease and other tumours such as primary gastrointestinal stromal tumours (GIST) is essential in determining the appropriate treatment [9].

Laparoscopic wedge resection is the treatment of choice for isolated small/medium gastric tumours (<7 centimetres) near the greater curvature of the stomach as it is associated with quicker recovery in comparison to open procedures [10]. Saidi et al. (2007) report one case where this resection technique was used in a patient with an isolated gastric metastasis of RCC origin, after which they remained diseasefree 18 months following surgery. Our patient is one of the longest surviving patients after laparoscopic wedge resection for isolated gastric RCC metastasis and remains disease-free 8 years post-surgery.

Subtotal and total gastrectomies are more frequently reported and are used to treat larger tumours or those which are localised within the antral or fundal regions of the stomach [2,11]. In the cases reviewed, all patients who underwent wedge resection in the absence of metastases to other organs were disease-free after 2-18 months with no evidence of further bleeding.

Endoscopic clipping is used to achieve haemostasis in upper GI bleeding, although it is also a technique used to localize gastric or oesophageal tumours to aid external beam radiotherapy [12]. Radiotherapy to gastric tumours is primarily utilised to palliatively treat symptoms of bleeding, pain and dysphagia [13,14]. To the best of our knowledge, there are no case reports on gastric metastases from renal carcinoma in which radiotherapy has been used as a treatment modality for cessation of bleeding.

Given the relatively small number of patients who develop gastric metastases from RCC, it would not be feasible to conduct trials to determine which interventions have the best outcomes. Hence, based on our experience and our literature review, we propose the following paradigm for treating gastric metastases from RCC primary (Figure 4)

surgery-Bleeding-Gastric

Figure 4: Treatment Paradigm for Management of Bleeding Gastric RCC Metastases.

Discussion of such cases in a multi-disciplinary setting is critical. It is thought that oncology patients who are discussed at such meetings often have better outcomes [15,16].

Conclusion

Gastric metastases in RCC are uncommon, but not as rare as once thought. They can cause significant haemorrhage and are generally associated with poor prognosis. Treatment should be patient-tailored depending on general condition at time of presentation, presence of extra-gastric metastases and the available resources and expertise. However, based on both our experience and the literature, we suggest that surgical intervention has good therapeutic and prognostic benefit in patients with isolated metastatic disease to the stomach. On the other hand, for those with widespread metastatic disease, other management options, if available, including embolization therapy, endoscopic submucosal resection and chemotherapy, should be considered. Furthermore, we advise that radiotherapy should also be considered as a viable option in the management of patients with bleeding lesions and concurrent metastases.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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