Diffuse Metastases Research Articles

Development of Isolated Hepatic Perfusion via the Operative and Percutaneous Techniques for Patients With Isolated and Unresectable Liver Metastases

The development of effective treatment strategies to provide durable control of isolated diffuse metastases to the liver is a major challenge in clinical oncology. The number of patients afflicted annually with isolated liver metastases is considerable; of the 156,000 patients diagnosed with colorectal cancer in 2009, it is estimated that up to 40,000 will develop liver metastases as the sole or dominant site of disease progression and of whom only 10% to 20% will have tumors amenable to resection. Patients with neuroendocrine cancers and ocular melanoma will frequently develop isolated and diffuse liver metastases as the dominant mode of tumor metastasis and, although less frequent, patients with other types of cancers such as cutaneous melanoma or breast cancer can occasionally develop isolated diffuse metastases to the liver.Isolated hepatic perfusion and percutaneous hepatic perfusion are under clinical evaluation for patients with diffuse isolated liver metastases from various solid organ cancers. Both share the advantages of intensifying treatment to the cancer-burdened organ of the body to improve efficacy and limit unnecessary systemic toxicity by selectively delivering high-dose therapeutic agents into the hepatic arterial system from which established metastases derive their predominant blood supply. In this article, we will review the history and early clinical development of isolated perfusion, the techniques of isolated hepatic perfusion and percutaneous hepatic perfusion, the current clinical results with isolation perfusion, and discuss the potential future clinical use of these approaches.

Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature

BackgroundGefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib.Case presentationTwo patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously.ConclusionWe speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

Metastatic Melanoma to Thyroid: A Case Report and Institutional Review

Abstract Objective To report a case of melanoma metastatic to the thyroid gland and to review our experience with secondary neoplasms of the thyroid. Methods We depict the presentation and treatment of the patient, illustrating pathologic and radiologic findings. All patients with pathologic confirmation of metastatic tumors of the thyroid undergoing thyroidectomy at the Massachusetts General Hospital were reviewed (1995- 2008). Results A 59-year-old male presented with malignant melanoma of the scalp. Two months following his melanoma excision and lymphadenectomy, he underwent a hemi-thyroidectomy for fine-needle aspirate positive solitary metastasis. He initially did well, but on follow-up was noted to have diffuse metastases and expired from his disease eight months following initial diagnosis. Institutional review revealed 13 additional patients with pathologically confirmed secondary thyroid tumors. Conclusions FNA remains an indispensable diagnostic tool. Palliation from local compressive symptoms is an indication for surgery and long-term survival is seen in some patients undergoing resection of isolated metastases.

Isolated metachronous cutaneous metastases from renal cell carcinoma

Sir, Cutaneous metastases from renal cell carcinoma (RCC) are unusual and its incidence has been reported to be 1-3.3%.[12] There is need for a high index of suspicion in evaluating a patient presenting with a skin tumor, which can be synchronous or metachronous.[23] They typically indicate coexistent disseminated disease and a poor prognosis. The scalp and face are the commonest sites of cutaneous metastases in RCC.[12] The proposed mechanisms of cutaneous metastatic dissemination include direct invasion from underlying neoplasm, implantation in an operative scar, lymphatic permeation, and hematogenous spread.[45] The clinical appearance of skin metastases can be of 3 types: nodular (majority), inflammatory, and fibrotic.[25] Cutaneous lesions may be flesh colored, but often range from erythematous red to violaceous hues. They are often multiple but may also present as solitary metastasis. The average interval from the appearance of skin lesions to death is reportedly 12.7 months.[25] The treatment options for such lesions are generally limited and supportive. Whereas diffuse metastases should be treated with appropriate systemic therapy, focal cutaneous metastases may be surgically excised or treated with radiotherapy or a combination of the two.[25] We report an unusual case of isolated metachronous cutaneous metastases from a low-stage RCC. Very few such case reports have been described in world's literature on the subject. Interestingly, this is the first reported case from India in which isolated metachronous cutaneous metastases, albeit at 2 locations, have been noted. A 62-year-old male patient presented a year ago with recurrent episodes of gross hematuria and right flank pain of 6 months duration. Contrast-enhanced computed tomography (CECT) of the abdomen showed a heterogenous right renal mass (12 Χ 10 cm) abutting the ascending colon and hepatic flexure [Figure 1]. There was no evidence of any lymphadenopathy and distant metastases. The patient underwent a right open radical nephrectomy. Histopathology revealed a clear cell variant of RCC, confined to the renal capsule, with tumor-free surgical margins (pT2 N0 M0). Three months postoperative follow-up physical examination, chest radiograph, and abdominal sonogram were normal. At 11 months of follow-up, the patient noticed asymptomatic, rapidly enlarging nodules on the chin and scalp, appearing simultaneously around a month prior to reporting to the hospital. Examination revealed a purplish colored fleshy nodule (2 Χ 2 cm) arising on the right parietal region of the scalp. There were similar 2 nodules on the chin (1Χ2 cm), which had a subcutaneous component [Figures 2 and 3]. On palpation, they were nonpulsatile, freely movable over underlying bones. Serum biochemical parameters, including liver function tests were normal. CECT of the abdomen, chest radiograph, and bone scan were also normal. Excisional biopsies of the nodules were performed, which were consistent with the diagnosis of metastatic deposits from RCC [Figures 4 and 5]. The patient was subsequently treated with systemic immunotherapy. At 9 months of follow-up after metastatectomy, the RCC patient is well and has no evidence of other metastases.Figure 1: Contrast enhanced computed tomography (CECT) of the abdomen showing an enhancing heterogeneous mass replacing the inferior pole of the right kidneyFigure 2: Two fleshy, reddish purple nodular metastatic cutaneous deposits on the chin.Figure 3: Metastatic cutaneous deposit on the scalpFigure 4: Photomicrograph showing part of epidermis with metastatic renal cell carcinoma in dermis (H and E, ×40)Figure 5: Photomicrograph showing a sheet of clear cells of metastatic renal cell carcinoma with distinct cellular outlines and centrally placed nuclei in the skin H and E, ×200Thus, patients with low stage RCC at the time of nephrectomy may also develop cutaneous secondaries, sometimes after several months. In these patients the role of biological response modifiers needs to be evaluated.

Ovarian Cancer Metastatic to the Breast Presenting as Inflammatory Breast Cancer: A Case Report and Literature Review

Background. Primary ovarian carcinoma with metastasis to the breast is rare, with only 39 cases reported in the current literature. Ovarian metastasis to the breast presenting as inflammatory breast carcinoma is even more infrequent, with only 6 cases reported.Case. We present a patient who developed metastatic inflammatory cancer of the breast from a stage IIIC papillary serous ovarian adenocarcinoma approximately 1 year after the original diagnosis. Pathologic analysis confirmed the origin of the tumor: a high-grade adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. In addition, the tumor was strongly positive on immunohistochemistry for CA-125, identical to the ovarian primary. The patient died of diffuse metastasis 5 months after the breast tumor was noted.Conclusion. Although ovarian metastasis to the breast presenting as inflammatory breast cancer is rare, it should be included in the differential diagnosis for any patient with a personal history of ovarian cancer. Accurate differentiation is necessary because treatment differs significantly for patients with ovarian metastasis to the breast, as compared with patients with primary inflammatory breast cancer. Ovarian metastasis to the breast confers a poor prognosis: patient survival ranged from 3 to 18 months, with a median survival of 6 months after the diagnosis of the breast metastasis.

Clinicopathological Properties of the Superficial Spreading Type Early Gastric Cancer

IntroductionWe investigated differences in characteristics between the superficial spreading type early gastric cancer (EGC) characterized by a wide and superficial extension and the common type EGC. Patients and MethodsBetween 1982 and 2008, we retrospectively reviewed clinical reports of patients with the EGC treated at Kochi Medical School. ResultsSixty-one patients (9.6%) out of 646 patients had the superficial spreading type EGC. The occurrences of diffuse type histology and lymph node metastasis were significantly greater in the superficial spreading type than in the common type. The incidence of EGC confined to the mucosa was significantly greater in the lymph node-positive superficial spreading type than in the lymph node-positive common type. ConclusionsIn patients with the superficial spreading type EGC, lymph node metastasis was more prominent regardless of the degree of tumor invasion. Therefore, appropriate extensive lymph node dissection and wide surgical resection are required for the curative resection of the superficial spreading type EGC.

Blood salvage and cancer surgery: should we do it?

In this edition of TRANSFUSION,1 a case series is presented where blood salvage was used during surgery for gynecologic malignancy. Commonly, blood salvage is avoided in cancer surgery due to a fear of creating disseminated metastasis from incorporating cancer cells into the shed blood and reinfusing them directly into circulation. In the case series presented here, diffuse metastasis did not arise shortly thereafter. While a case series does not prove the safety of this technology during oncologic surgery, it does provide an opportunity to review the data regarding this contraindication.

Demonstration of Diffuse Leptomeningeal Metastasis in a Treated Case of Medulloblastoma With F-18 FDG PET/CT

A 20-year-old man diagnosed as a case of desmoplastic cerebellar medulloblastoma had undergone shunting of the lateral ventricles and resection of the mass followed by postoperative irradiation to the entire neuraxis. There was evidence of residual disease in the posterior fossa on craniospinal MRI for which he had undergone cranial radiation and adjuvant chemotherapy. Two serial cranial MRI's (4 months apart) were done following this and though the lesion in the posterior fossa remained essentially the same with no evidence of progression the patient had a general decline in his ability to function and he was sent for a FDG-PET/CT study to evaluate for recurrent disease. The study revealed abnormal FDG uptake along the entire length of the thecal sac from the cervical to the lumbosacral level suggesting the possibility of metastasis. Spinal MRI with gadolinium contrast confirmed diffuse leptomeningeal metastasis. Thus FDG-PET/CT is a useful tool to evaluate for metastasis in medulloblastoma.

Dormant Metastases in Medullary Thyroid Carcinoma.

Report on a patient in whom an extensively metastasizing medullary carcinoma of the thyroid was diagnosed at the age of 32 years. Noteworthy in her case history were watery diarrheas that had persisted for two years, suggesting that the medullary thyroid carcinoma had already existed for some time. Besides locoregional lymph node metastases, small foci of diffuse pulmonary metastases with lymphangitis carcinomatosa as well as osteoblastic skeletal metastases were present and intramammary metastases were detected later. The patient died from bilateral pleuropneumonia with empyema formation at the age of 47 years after an observation period of 15 years. During that period, no major changes in the pattern of metastatic spread were observed and one may therefore speak of "dormant" metastases in this case, although some manifestations showed increases and decreases in size.

Secondary Tumors and Tumorlike Lesions of the Peritoneal Cavity: Imaging Features with Pathologic Correlation

Tumors and tumorlike lesions that secondarily involve the mesothelial or submesothelial layers of the peritoneum are a diverse group of disorders that range in biologic behavior from benign to highly malignant. The anatomy of peritoneal ligaments and mesenteries and the normal circulation of peritoneal fluid dictate location and distribution of these diseases within the peritoneal cavity. Peritoneal carcinomatosis is the most common secondary tumor to affect the peritoneal cavity. When it arises from carcinomas of the gastrointestinal tract or ovary, the prognosis is grave. However, when low-grade mucinous adenocarcinoma of the appendix spreads to the peritoneal cavity, the consequence is typically pseudomyxoma peritonei, which is a clinical syndrome, characterized by recurrent and recalcitrant voluminous mucinous ascites due to surface growth on the peritoneum without significant invasion of underlying tissues. Carcinomas from elsewhere in the body, as well as lymphomas and sarcomas, may also produce diffuse peritoneal metastasis. Granulomatous peritonitis is the consequence of disseminated infection such as tuberculosis or histoplasmosis, foreign materials, or rupture of a tumor or hollow viscus. Finally, a group of benign miscellaneous conditions that range from common disorders such as endometriosis and splenosis to very rare conditions such as gliomatosis peritonei and melanosis may also affect the peritoneum diffusely. Secondary tumors and tumorlike lesions of the peritoneum have overlapping imaging features when compared with each other and primary peritoneal tumors. Knowledge of peritoneal anatomy, normal fluid circulation within the peritoneal cavity, and clinical and pathologic features of secondary peritoneal lesions is essential for identification of these lesions.

Melorheostosis with renal arterio-venous malformation: A case report with review of literature

Melorheostosis, also known as Leri′s disease and flowing periosteal hyperostosis, is a rare cause of pain and stiffness in a limb. The appearance is of "candle greasing" down one side of one or several bones of the body. We describe a case referred to tertiary care center with suspicion of renal cell carcinoma with diffuse bone metastasis. After reassessment, the patient was diagnosed melorheostosis with renal AV malformation. He was reassured about the benign nature of the disease and is asymptomatic.

Cutaneous matastasis from sino-nasal malignant melanoma — a rare case report

To report a case of disseminated cutaneous metastasis from malignant melanoma of sino-nasal region. A 53-year-old man from rural parts of West Bengal presented with progressive nasal obstruction. CT scanning was done to know the extent of the mass and punch biopsy from the mass was performed. Malignant melanoma of sino-nasal region was diagnosed and chemotherapy was started. The patient developed cutaneous deposits after two cycles of chemotherapy. The patient developed cutaneous deposits during the course of chemotherapy. Excision biopsy from cutaneous deposits revealed malignant melanoma. A rare case of diffuse cutaneous metastasis of malignant melanoma is presented here along with review of literature.

A Rare Case of Breast Cancer Metastasis Presenting as Linitis Plastica of Stomach and Colon

Purpose: 71-year-old Hispanic female patient underwent screening colonoscopy with complaints of recent onset of constipation and weight loss. At the same time an upper endoscopy was done to evaluate for decreased appetite and early satiety. She had significant past medical history for recurrence of breast cancer with diffuse skeletal metastasis 2 years ago after a decade of cancer free period. Currently, she was receiving palliative chemotherapy. On examination, she appeared cachectic and pale. Laboratory examination disclosed normocytic anemia, with a Hb level of 10.5 g/dL (normal range for Hb in our institution is 11.5–15.5 g/dL). Colonoscopy revealed an irregular configuration of the mucosal surface, luminal narrowing, and poor distensibility in the mid-transverse colon (Fig. A). Multiple biopsies were obtained. Histopathologic examination of the biopsy specimen revealed colonic mucosa with metastatic adenocarcinoma, morphologically consistent with lobular carcinoma of breast (Fig. B). EGD revealed thickened gastric folds; multiple biopsies were obtained. Histopathologic examination of the gastric biopsy specimens also revealed metastatic adenocarcinoma from breast. Extrahepatic gastrointestinal metastasis from breast cancer is uncommon. Metastases to the stomach and small bowel from breast cancer are reported to be more frequent than colonic and rectal involvement. Two reviews dealing with metastatic breast cancer have reported the involvement of colon in about 4% of the patients. Lobular carcinoma is the most common histological type of breast cancer that metastasizes to the colon and rectum. It is important to realize that patients with known breast cancer, especially of the lobular type, with vague, nonspecific abdominal signs and symptoms, particularly of an obstructing nature should be endoscopically screened for gastrointestinal metastases.

Pilomyxoid Astrocytoma of the Spinal Cord with Cerebrospinal Fluid and Peritoneal Metastasis

Pilomyxoid astrocytoma (PMA) is a recently described rare tumor which is a variant of pilocytic astrocytoma (PA). It exhibits a more aggressive behavior than PA. Spinal cord PMA has been reported in two articles in the past and none of the reported case had extraneural metastasis. We report on a female child with cervical cord PMA with diffuse leptomeningeal metastasis involving the brain and spinal cord. Two years later she presented with peritoneal carcinomatoses which was consistent with metastatic tumor via a ventriculoperitoneal (VP) shunt. This case confirms the aggressive behavior of PMA and makes clinicians aware of the possibility of extraneural, peritoneal metastasis through a VP shunt.

R413 – KITENIN Enhances Invasion and Metastasis in FOM Cancer Model

Problem KAI1 is a metastatic suppressor gene. The expression of KAI1 in cancer cells results in reduced cell motility and invasiveness. A cDNA clone of VANGL1, a member of the tetraspanin protein family that specifically interacts with the COOH-terminal cytoplasm domain of KAI1, was isolated and renamed KITENIN (KAI1 COOH-terminal interacting tetraspanin). KITENIN is reported to promote metastasis in a mouse colon cancer model. The purpose of this study was to investigate tumor invasiveness and early lung metastasis by KITENIN in murine floor of mouth cancer model. Methods The cDNA of KITENIN and the vector only were transfected into the SCC VII (mouse squamous cell carcinoma cell line) cells. The transfections were performed using the FuGENE 6 transfection reagent. The suspension of 5 × 105/? viable KITENIN- or vector-transfected SCC VII cells were injected into the floor of mouth of C3H/HeJ syngeneic mice deep to the mylohyoid muscle via an intra-oral approach. From the 1st week to 6th week after injection, tumor, lung, liver, and brain tissues were obtained from six mice each group every week and were evaluated under the light microscope. Results On each group, the tumor invaded to superficial musculature of floor of mouth, deep musculature of floor of mouth, salivary gland, perineural tissue, bone, and skin sequentially. Lung metastases started from peripheral and localized region and moved to central and diffuse lung tissues. Earlier and more aggressive tumor invasion to deep floor of mouth musculature, salivary gland, perineural tissue, bone, and skin was observed in KITENIN-transfected group than in vector group. Earlier and more diffuse lung metastasis was observed in KITENIN group. Conclusion KITENIN enhanced tumor invasion and lung metastasis in murine floor of mouth squamous carcinoma model. Significance An antisense KITENIN strategy could be used to inhibit distant metastasis and progression in head and neck squamous cell carcinoma. Support This study was supported by a grant CUHRICM-CRI07038-1.

Prenatal diagnosis of infantile fibrosarcoma with diffuse metastases

Prenatal diagnosis of infantile fibrosarcoma with diffuse metastases

Hypertrophic osteoarthropathy as the cause of a super scan of the bone in a patient with prostate cancer: a case report

IntroductionProstate cancer is known to have a tendency to metastasize to bone. Skeletal scintigraphy can be used to show multiple lesions. Diffuse metastasis, which is not infrequent in prostate cancer, can also be suspected on the basis of a 'super scan'. However, this phenomenon in nuclear medicine has several other causes that need to be considered.Case presentationA patient with a history of prostate cancer presented with pleural fluid, peripheral edema and bone pain. A super scan of the bone was found which suggested diffuse skeletal metastasis of the prostate cancer but the patient also had a prostate specific antigen level which was not compatible with this diagnosis. Further investigations revealed the paraneoplastic phenomenon of hypertrophic osteoarthropathy, related to an incurable carcinoma of the lung, to be the cause of the super scan.ConclusionA super scan is characterized by a high bone to soft tissue ratio on skeletal scintigraphy, with a uniform symmetrical increase in bone uptake and diminished to absent renal visualization ('absent kidney sign'). It can be seen in a variety of diseases in which there is a diffusely increased bone turnover. Diffuse skeletal metastasis of a well-differentiated prostate carcinoma is unlikely to be the cause of a super scan when the prostate specific antigen level is not elevated. This is the first report of a super scan due to pulmonary hypertrophic osteoarthropathy which can be seen in lung carcinoma and other pulmonary diseases.

Treatment of inoperable liver metastases: preliminary results with intrahepatic chemotherapy via a new type of indwelling catheter (author's transl)

Intra-arterial liver perfusion of cytostatic drugs via an indwelling double-lumen polyurethane catheter was undertaken in 17 patients with diffuse metastases involving 50-70% of the liver and previously treated by radical local resections. Treatment continued over 3-20 months (mean 8.4 months). In ten patients with colorectal carcinoma treatment lasted for 7 months, follow-up for a mean of 14 months (range 5-24 months), and the one-year survival time (using the actuarial method) was 79 +/- 26%. The toxicity was well controllable. It is concluded that this form of treatment improves quality of life in such patients.

Standardized surgical concept for the diagnosis and therapy of Zollinger-Ellison syndrome

Between 1987 and 1991, 16 patients (13 females, three males; mean age 52.4 [33-73] years) with Zollinger-Ellison syndrome (ZES) were treated according to a standardized surgical concept. The diagnostic work-up consisted of measuring serum gastrin levels, pre-operative localization by ultrasound and abdominal computed tomography, as well as extensive staging by laparotomy. As complete a tumour resection as possible was the aim of treatment in 15 patients, while in one patient it was to reduce the tumour mass. In six patients who had resection of a solitary tumour there was no evidence of recurrence after 6-42 months of follow-up. Exploration of the duodenum made it possible to identify and then remove a small gastrinoma of the duodenal wall in three patients. No gastrinoma was found in one patient despite extensive exploration. In a further four patients the laparotomy was purely exploratory, because diffuse metastasization was found. In four patients the primary tumour and, where present, the regional lymph nodes were removed, but the signs of ZES persisted, i.e. the intervention was merely palliative. In one female patient, reduction of tumour mass was necessary because the symptoms could not be controlled by conservative measures: she died postoperatively from toxic hepatitis. This experience indicates that standardized surgical intervention achieves potentially curative results in nearly 40% of patients. Including the duodenum in the surgical exploration allows the identification of even small gastrinomas of the duodenal wall. It is concluded that all patients with ZES but no evidence of diffuse metastases should undergo surgical treatment.

Clinical Challenges and Images in GI

Question: A 29-yearold white man was brought to our department with a presumptive diagnosis of diffuse hepatic metastasis. He was complaining of anorexia and abdominal right upper quadrant discomfort over the last 2 months. On physical examination he had a nodular liver border, 2-cm below the right costal margin. Abdominal ultrasonography and computed tomography were performed, revealing the presence of multiple nodules diffusely distributed throughout the liver parenchyma. The patient referred a history of asthma, recently medicated with montelukast, and denied alcohol intake or hepatotoxic drug exposure. Liver tests demonstrated slightly elevated aspartate aminotransferase (64 U/L), alanine aminotransferase (98 U/L), and -glutamyltransferase (270 U/L) levels. The remaining blood tests (tumor markers—-fetoprotein, carcinoembryonic antigen, and CA19.9; viral serologies; autoimmunity; ceruloplasmine; HFE genotype), as well as upper GI endoscopy and ileocolonoscopy, were normal. The subsequent investigation with abdominal magnetic resonance imaging and magnetic resonance angiography (Figure A, B) revealed an abnormal vascular structure (arrows) and elucidated this clinical situation. What is the most likely diagnosis? Look on page 000 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Acknowledgments: The authors thank Dr Carlos Pina Vaz for providing the radiological films.