Iodine-131-MIBG therapy of a patient with carcinoid liver metastases

Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.     

Induced hypertensive chemotherapy with angiotensin-II for liver metastases from gastric cancer

The theoretical purpose of induced hypertensive chemotherapy used together with injection of Angiotensin-II is to increase the delivery of anticancer drug to the target tumor tissue by increasing blood flow in the tumor. Angiotensin-II (0.1 mg) was dissolved in 50 ml of normal saline, and given through a peripheral vein by a microinfusion pump. When systolic pressure rose to about 140 to 150 mmHg, Mitomycin C (10 to 20 mg/body) was given for 10 minutes via implanted port, whose tip was located in hepatic artery, followed by continuous infusion of 5-FU at 250 mg/day for 5 days. Response could be measured in 4 of all cases (66.7%). CR was found in 2 and PR in 2. Bone metastases or systemic lymph node metastases occurred after a few months in one CR case and one NC case. We concluded that this mode of chemotherapy was a useful measure for the treatment of liver metastases from gastric cancer.     

Multidisciplinary treatment for colorectal liver metastases

The liver is an large immunologic organ with liver-associated macrophages (Kupffer cells) and natural killer-like primitive T cells. As these effectors are activated by interleukin-2 (IL-2), we have administered IL-2-based hepatic arterial infusion therapy in the treatment of patients with liver metastases of colorectal cancer. Patients with unresectable liver metastases were administered IL-2 7 x 10(5) U and 5-fluorouracil (5-FU) 250 mg/day as a continuous infusion, with a bolus injection of mitomycin C (MMC) 4 mg once weekly. Of 25 patients treated with this regimen, 19 achieved complete or partial responses (response rate: 76%). A multi-institutional randomized trial following the pilot study showed reproducible favorable results. For patients with resectable metastases, we have administered this infusion therapy for the prevention of cancer recurrence in the liver. Patients who had undergone curative hepatectomy received IL-2 1.4 to 2.1 x 10(6) U, 5-FU 250 mg and MMC 2 to 4 mg weekly for 6 months. Of 18 patients, 12 are alive disease-free, and the 5-year overall survival rate is 75%. Recurrent cancer has developed in 6 of the 18 patients; however, no patients had recurrence in the residual liver. We believe that liver metastases of colorectal can be controlled by this multimodal treatment.     

Multimodality treatment for retinoblastoma in children

A comprehensive programme was developed for the treatment of uni- and bilateral retinoblastoma in children with due regard to the disease stage by the TNM system. The use of the current sources of teletherapy and cyclic polychemotherapy expanded indications for organ-saving therapy at most common stages. Treatment by the program was performed in 202 patients, including 125 children with unilateral damage and 77 with bilateral damage. An attempt made treat 140 (75%) children at the first stage. More than 70% of cases were diagnosed as having disease stage T3 in one or two stage, while such patients underwent ocular enucleation. A complete or partial (more than 50%) tumor regression without signs of its progression for 2 years or more was achieved in 62% of cases. At the first stage of therapy, conservative therapy insignificantly affected the children's longevity in uncomplicated cases, which is particularly important in bilateral involvement, while this preserved the organ of vision in more than half the patients (62%). Five-year survival was 92 and 82% in unilateral retinoblastoma surgically treated and untreated, 83 and 84%, respectively. Adequate multimodality treatment brought about low incidence rates of recurrence and metastasis (10%) in conservative therapy and 7.7% among all patients.     

Primary hepatic carcinoid tumor

A case of primary carcinoid tumor arising in the liver of a 69 year old woman with no endocrine symptoms is reported. Histopathologically, the tumor was diagnosed initially as a hepatocellular carcinoma in the biopsy specimen, and was shown subsequently to be a carcinoid tumor, demonstrating diffuse positive staining with Grimelius method. Mucin stained with periodic acid-Schiff (PAS), alcian-blue, and mucicarmine, and was shown partially in the glandular structures. Immunohistochemically, most of the tumor cells stained positively for chromogranin-A, epithelial membrane antigen (EMA) and neuron specific enolase (NSE). Ultrastructural examination revealed electron-dense core granules, measuring 40-120 nm in diameter in some of the tumor cells. Intensive and careful searches pre- and post-operatively revealed no other primary source of tumor other than the liver. The patient was reported well with no symptoms 3 1/2 years after the operation. This case is considered to be a primary hepatic carcinoid tumor. The recent literature is reviewed, and the possible histogenesis of hepatic carcinoid tumor is discussed.     

Pancreas carcinoid with extensive liver metastasis--simultaneous excision

BACKGROUND: While patients' needs for adequate preoperative information are generally recognized, data evaluating the effectiveness of the consultation before laparoscopic cholecystectomy have not been published until today. This prospective study was performed to investigate the success of preoperative information. METHODS: A combination of oral and written information was given to all patients in two interviews. Information concentrated on indications for surgery, operative procedures, and risks. Patients were asked to answer questionnaires 5 days after the operation. RESULTS: From January 1996 to January 1997, 200 patients were interviewed. Ninety-seven percent indicated to wish detailed information. Eighty-four percent indicated a high level of satisfaction with the presented information. While the levels of knowledge concerning indications for surgery and procedures were satisfactory in 85 and 51% respectively, only 30% were able to name at least one risk factor of laparoscopic cholecystectomy. CONCLUSION: This study demonstrated that patients' evaluation of their surgical knowledge and the process by which it was communicated to them did not correspond to their ability to recall this information after surgery.     

Rectal carcinoid tumor associated with the Peutz-Jeghers syndrome

A 59-year-old female underwent mastectomy for right breast cancer in November 1992. She received tamoxifen and anthracycline-containing chemotherapy as adjuvant therapy. In and after September 1994, she developed loco-regional recurrences five times in total, each of which was treated with surgery and conventional combination chemotherapy. In April 1997, she developed liver metastasis, which was refractory to biochemical modulation therapy (low-dose cisplatin + 5-FU). We, therefore, treated her six times with docetaxel 80 mg, which resulted in partial response of the liver metastasis and brought about a marked decrease in serum CA15-3 levels. Adverse effects of docetaxel were grade 3 alopecia and leucocytopenia. She has been well without re-growth of the liver metastasis for over five months.     

Metastasized carcinoid tumor treated with interferon and octreotide

The carcinoid tumours are rare forms of the gastrointestinal tumours (they make up 2%), though lately they have shown an upward tendency. Among different types of treatments of the carcinoid tumours in non metastatised cases, the surgical intervention stands first on the list. But when symptoms emerge, most of the tumours have metastases, for which there are various types of treatments. The authors introduce the combined therapeutical possibilities in connection with metastatised carcinoid tumours. A combination of octreotid and interferon is used in the course of the treatment. Authors introduce the therapy's indications and experiences gained during the follow up of events.     

Autoimmune polyglandular failure associated with malabsorption and gastric carcinoid tumour

A 21-year-old female with autoimmune polyglandular failure (APG) manifested by insulin-dependent diabetes mellitus (IDDM), hypothyroidism and pernicious anaemia developed severe malabsorption due to exocrine pancreatic insufficiency. Supplemental pancreatic enzymes resulted in marked improvement of steatorrhea. There was also an incidental finding of gastric carcinoid tumour. We identified only 13 other patients in our institution with either type 2 or 3 APG, one of which had significant steatorrhoea. Another patient with IDDM, hypothyroidism and pernicious anaemia had an asymptomatic gastric carcinoid tumour. The possible mechanisms for malabsorption in APG are discussed.     

Isolated lung perfusion with tumor necrosis factor for pulmonary metastases

BACKGROUND: A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. METHODS: Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons. RESULTS: There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). CONCLUSIONS: Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.     

Atypical carcinoid tumor of the thymus

We report a male patient with atypical carcinoid tumor diagnosed by anterior mediastinotomy and biopsy after a mass was observed by chance on a chest film. The presence of neuroendocrine markers, notably chromogranin, cytokeratin, synapto-physin and neuro-specific enolase, facilitated diagnosis. Because the tumor was infiltrative, full surgical excision and radiotherapy to the mediastinum (50 Gy) were provided. We describe the incidence, clinical presentation, diagnosis, treatment and prognosis of these tumors.     

Measurement of response to treatment in colorectal liver metastases

Assessment of tumour response to chemotherapy is important when assessing efficacy of treatment and comparing differing therapeutic regimens. Percentage hepatic replacement (PHR) is commonly used to assess response to treatment of colorectal hepatic metastases. PHR is dependent not only on tumour volume, but also on hepatic parenchymal volume. The effect of tumour growth on hepatic parenchymal volume is unclear but is of importance owing to its effect on PHR. We assessed tumour and hepatic parenchymal weights in an animal tumour model using dissection, and tumour and hepatic parenchymal volumes in patients with colorectal hepatic metastases using CT scanning, in order to establish how hepatic parenchyma varied with change in metastasis size. There was no significant correlation between tumour and liver parenchyma in either the animal model (r = -0.03, P > 0.05) or the patient study (r = 0.3, P < 0.05). This suggests that hepatic parenchymal volume was preserved in the presence of increasing tumour volume. In a further study of computerised tomographic (CT) scans before and after treatment in patients whose tumours either responded to chemotherapy or continued to grow, change in PHR (median proportion of PHR change = 0.40) significantly (P = 0.04) underestimated the change in tumour volume (median proportion of tumour volume change = 0.56), particularly at higher (> 400 ml) volumes. There was good correlation between change in tumour volume and WHO criteria in assigning patients to tumour growth, stable disease or tumour response categories. This study suggests that, in clinical trials comparing colorectal liver metastasis treatments, metastasis volume and not PHR should be used to assess extent of disease and the effect of treatment.     

Hepatic resection for colorectal liver metastases

The lack of other effective treatment for colorectal liver metastases makes hepatic resection a primary treatment consideration. Between January 1980 and December 1990, 26 selected patients with liver colorectal metastases who underwent hepatic resection were reviewed. The age, sex, site of primary lesion, histological grade, lymph node involvement, location, size, and number of hepatic metastases, type of hepatic resection, and preoperative CEA blood levels were documented. Complete removal with histologically negative resection margins were accomplished in 24 patients. The extent of resection performed was hepatic lobectomy in 12 patients. Segmentectomy in eight patients, and wedge resection in four patients. The 5-year survival rate was 30.5 per cent. Patients with metachronous metastases showed a better survival rate than those with synchronous lesions--46.6% versus 13.6% respectively (P = 0.08). None of the other factors studied showed a significant effect on survival. All patients were followed from the time of hepatic resection to the time of this study or death. During a median follow-up of 30.9 months, 20 patients developed recurrence of their disease (60 per cent in the liver). There was no perioperative mortality. Morbidity arose in 66.6 per cent of patients, with a majority of the complications being minor. We conclude that hepatic resection can be performed safely enough to be recommended in selected patients.     

Middle ear carcinoid: an indolent tumor with metastatic potential

5-lodo-2'-deoxyuridine (IUdR), a thymidine analog, is transported through cell membrane and is incorporated into newly synthesized DNA during the S phase of mitotic cells. In rapidly growing brain tumors such as glioma, radioiodinated IUdR may be an efficient diagnostic as well as therapeutic agent and may provide a means to determine the proliferative activity of the tumor. IUdR was labeled with 123I (t1/2 = 13.3 h, gamma = 159 KeV, 83%) and injected i.v. into nude mice bearing human colorectal carcinoma LS174T. At 3 and 20 h postinjection, tumor uptake was 2.6 +/- 0.9% and 0.5 +/- 0.2%, respectively, of the injected dose per gram of tissue. Radioactivity in other tissues also declined as a function of time, but much more rapidly, yielding tumor-to-blood ratios of 16.4 +/- 2.2 and tumor-to-muscle ratios of 22.2 +/- 7.7 at 20 h postinjection. Of the radioactivity in the tumor, 12.6 +/- 0.9% was bound to DNA at 3 h and 25.2 +/- 2% at 20 h postinjection. A high (7 +/- 1.1% i.d.) uptake in thyroid at 3 h postinjection indicated dehalogenation in vivo.     

Choroidal metastases of a bronchial carcinoid tumor. Review of cases in the literature. A case report]

To assess the clinical significance of silent myocardial ischemia (SMI) in the elderly, 113 patients with stable angina who showed ischemic ST depression during treadmill stress testing were studied by dipyrimadole thallium imaging and coronary arteriography. They were divided into two groups: 44 patients with silent ST depressions and 69 patients with painful ST depressions. The groups were compared for scintigraphic and coronary arteriographic features as well as prognosis. There was a significantly greater proportion of older patients (> or = 65 years) in the group with SMI (64%) than in the group with painful ischemia (38%) (p < 0.01), although there was no difference in the mean ages of the two groups. The prevalence of multivessel coronary stenosis was not significantly different between the two groups (45% in the SMI group and 61% in the group with painful ischemia). Treadmill stress testing showed no differences in exercise duration, maximal heart rate, maximal systolic blood pressure, or maximal ST depression between the two groups. Dipyrimadamole thallium imaging revealed similar results in the site of reversible defects (RD), i.e. 76% in the anterior area and 24% in the inferior area in patients with SMI, and 83% in the anterior area and 17% in the inferior area in patients with painful ischemia. However, the size of RD was significantly smaller in patients with SMI, i.e. 14.6 +/- 6.1 segments in patients with SMI and 18.7 +/- 8.3 segments in patients with painful ischemia (p < 0.05). Although a significantly higher proportion of patients with painful ischemia (48%) underwent PTCA or CABG as their initial therapy as compared to those with SMI (16%), there was no significant difference in the cardiac event rate between the two groups initially treated medically. Among patients with stable angina, those with SMI may have a smaller amount of ischemic myocardium and may be older in a greater proportion than those with painful ischemia. Dipyrimadole thallium imaging is useful in the assessment of SMI in the elderly.     

Bronchial carcinoid tumor metastatic to the breast

We report a case of bronchial carcinoid that initially manifested as metastatic tumor in the breast. An exhaustive search for the primary tumor yielded the finding of a large right lung mass. Subsequent histopathologic examination of the resected lung and breast tissues confirmed the lung cancer as a primary tumor and the breast tumor as metastatic disease.     

Results of resection of gastric cancer with distant metastases

BACKGROUND/AIMS: The present study was carried out in order to examine the outcome of resection in cases of gastric cancer with distant metastases. METHODOLOGY: The survival rates of two hundred and eighty-one patients who had undergone resection for primary carcinomas of the stomach, and who had distant metastases according to the TNM classification, were studied. RESULTS: The 5-year survival rates for patients with metastasis to the peritoneum or group 3 nodes were 8.9% and 15.3% respectively and were significantly higher than the survival rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or to more than one site among the liver, lymph nodes and peritoneum (3.5%). Moreover, the 5-year survival rates for patients with metastasis to the peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively, when curative surgery was performed. CONCLUSIONS: The findings of the present study suggests that metastases to the adjacent peritoneum or group 3 nodes have a greater chance of being cured using radical surgery, and that gastrectomy with extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there is no gross evidence of metastasis to the distant peritoneum, liver or group 4 nodes.