[A Case of Malignant Lymphoma Undergoing HAI Treatment for Multiple Liver Metastases of Carcinoid That Appeared about Nine Years after Resection of Rectal Carcinoid with Liver Metastases].

The present case pertained to a 70-year-old woman. The fecal occult blood test was positive. Colonoscopyrevealed rectal cancer. She underwent the first operation of low anterior resection. Pathological diagnosis was carcinoid, se, ly2, v0, n1. Approximately2 months later, multiple liver metastases were found. Because of strong enhancement at angiography, transarterial chemoembolization(TACE)was selected. After 3 rounds of TACE, we operated the residual liver metastasis approximately1 year and 7 months after the first operation. However, approximately8 years and 9 months after the first operation, multiple liver metastases were found again. Hepatic arterial infusion(HAI)was chosen because tumors showed weak en- hancement on CT. First, we tried high-dose HAI(5-FU 1 g/dayat 1-3 and 5-7, amount: 6 g/week), and liver metastases was almost in CR. However, extrahepatic metastasis was found on PET-CT. Because of rapid growth, we operated the growing lymph node. Pathological diagnosis was diffuse large-cell type B-cell malignant lymphoma. Thus, we extended the interval of HAI(weekly, biweekly, and monthly)and simultaneously4 courses of R-THP-COP(R: rituximab, THP: pirarubicin, C: cyclophosphamide, O: vincristine, P: prednisolone)therapyfor malignant lymphoma was administered. She is now an outpatient. Liver metastases continue to be in CR at approximately1 year and the IL-2R value is almost within normal range.

Outcomes in Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is often misclassified and mistreated due to mixed histologic features. In general, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard of care for peritoneal carcinomatosis (PC) from mucinous appendiceal tumors; however, in PC from GCA, data are limited and the role of CRS/HIPEC is controversial. We report outcomes in PC from appendiceal GCA treated with CRS/HIPEC. PATIENTS AND METHODS: A prospective institutional database of 391 CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2018 was reviewed. Twenty-seven patients with GCA were identified. Perioperative variables were described. Survival was estimated using the Kaplan-Meier method. RESULTS: GCA occurred in 7% (27/391) of appendiceal CRS/HIPEC patients. Seven (26%) cases were aborted. Two patients underwent a second CRS/HIPEC for peritoneal recurrence. Median age at diagnosis was 53 years (range 39-72 years), and 12 (60%) were female. All underwent previous surgery. Seven (35%) had prior chemotherapy and received a median of 5 cycles (range 3-8). Median PCI was 6 (range 1-39). Complete cytoreduction was achieved in 95% (19/20). Grade III complications occurred in three (15%) patients, and no perioperative deaths occurred. Median follow-up was 97 months. Overall survival at 1, 3 and 5 years was 100%, 74% and 67%, respectively. Progression-free survival at 1, 3, and 5 years was 94%, 67% and 59%, respectively. CONCLUSION: CRS/HIPEC should be considered as the main treatment option for patients with PC from appendiceal GCA. When performed at a CRS/HIPEC specialty center, 5-year OS of 67% can be achieved.

Role of Adjuvant Chemotherapy in Pulmonary Carcinoids: An NCDB Analysis.

BACKGROUND/AIM: Typical carcinoids (TC) and atypical carcinoids (AC) are rare diseases. A paucity of randomized studies and disagreements among various guidelines makes the management challenging. PATIENTS AND METHODS: Using codes for TC (8240) and AC (8249) in the National Cancer Database (NCDB), all surgically resected cases from 2004-2014 were included to evaluate the need for adjuvant chemotherapy. RESULTS: A total of 6,673 cases were included, 88% were TCs and 12% were ACs. From 2004 to 2014, the proportion of TCs went up from 1.3% to 1.8% and ACs from 0.1% to 0.3% of all lung malignancies. TC patients did well with surgery alone in all stages. AC patients with stage I [5-year overall survival (OS) - 84% vs. 52%; S vs. S+CT] and stage II disease (5-year OS - 81% vs. 55%; S vs. S+CT) showed better OS trend with surgery alone, while stage III patients showed some benefit with the use of adjuvant chemotherapy (5-year OS - 46% vs. 54%; S vs. S+CT). These results supported the National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: No benefit was seen from adjuvant chemotherapy in TCs. While the adjuvant therapy may add benefit in stage III AC, the numbers are small and did not reach statistical significance.

Adenocarcinoma Ex-Goblet Cell: a Retrospective Experience.

PURPOSE: Adenocarcinoma ex-goblet cell carcinoids (AGCCs) are rare appendiceal tumors with mixed neuroendocrine and glandular features. They tend to behave more aggressively than typical carcinoid tumors, affect younger patients, and have a greater predilection for spreading to the peritoneum. Outcomes of AGCC patients treated with chemotherapy, extrapolated from colon cancer regimens, in the adjuvant or metastatic setting have not been explicitly reported. We sought to explore outcomes of AGCC patients with either local disease treated with adjuvant FOLFOX or metastatic disease treated with FOLFOX/FOLFIRI post-cytoreductive debulking (or CRS plus HIPEC in the peritoneal-limited setting). METHODS: We performed a single-institution retrospective analysis of 23 pathologically identified AGCC patients from Vanderbilt University Medical Center treated with chemotherapy in either the adjuvant or metastatic settings. Each patient's tumor was categorized as group B or group C based on the criteria from Tang et al. Median progression-free survival (PFS) or disease-free survival (DFS) (in the curative setting) and overall survival (OS) were determined for each patient and specified patient subgroup. RESULTS AND CONCLUSION: AGCC patients who were treated with FOLFOX chemotherapy in the adjuvant setting or FOLFOX/FOLFIRI in the metastatic setting experienced prolonged PFS, DFS, and OS. Five patients with peritoneal-limited disease treated with CRS plus HIPEC have not yet reached median PFS or OS. While small sample size, patient selection, and retrospective nature limit the generalizability of findings from our analysis, the efficacy signals we observed suggest prospective evaluation with chemotherapy and CRS plus HIPEC is warranted in AGCC patients.

Outcomes of Surgical and Chemotherapeutic Treatments of Goblet Cell Carcinoid Tumors of the Appendix.

BACKGROUND: Goblet cell carcinoids (GCCs) of the appendix are rare mucinous neoplasms, for which optimal therapy is poorly described. We examined prognostic clinical and treatment factors in a population-based cohort. METHODS: Patients diagnosed with GCC from 1984 to 2014 were identified from the British Columbia Cancer Agency and the Vancouver Lower Mainland Pathology Archive. RESULTS: Of 88 cases with confirmed appendiceal GCCs, clinical data were available in 86 cases (annual population incidence: 0.66/1,000,000). Median age was 54 years (range 25-91) and 42 patients (49%) were male. Metastasis at presentation was the strongest predictor of overall survival (OS), with median OS not reached for stage I-III patients, and measuring 16.2 months [95% confidence interval (CI) 9.1-29] for stage IV patients. In 67 stage I-III patients, 51 (76%) underwent completion hemicolectomy and 9 (17%) received adjuvant 5-fluorouracil-based chemotherapy. No appendicitis at initial presentation and Tang B histology were the only prognostic factors, with inferior 5-year recurrence-free survival (53 vs. 83% with appendicitis, p = 0.02; 45% Tang B vs. 89% Tang A, p < 0.01). Of 19 stage IV patients, 10 (62.5%) received 5-fluorouracil-based chemotherapy and 11 (61%) underwent multiorgan resection (MOR) ± hyperthermic intraperitoneal chemotherapy (HIPEC). Low mitotic rate and MOR ± HIPEC were associated with improved 2-year OS, but only MOR ± HIPEC remained significant on multivariate analysis (hazard ratio 5.4, 95% CI 1.4-20.9; p = 0.015). CONCLUSIONS: In this population-based cohort, we demonstrate excellent survival outcomes in stage I-III appendiceal GCCs and clinical appendicitis. Hemicolectomy remains the standard treatment. In metastatic disease, outcomes remain poor, although MOR ± HIPEC may improve survival.

Curative Surgical Resection as a Component of Multimodality Therapy for Peritoneal Metastases from Goblet Cell Carcinoids.

BACKGROUND: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown. METHODS: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox-regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms. CONCLUSIONS: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach.

Systemic chemotherapy (SC) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal mucinous carcinomatosis of appendiceal origin (PMCA).

BACKGROUND: The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA. METHODS: 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated. RESULTS: Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC. CONCLUSIONS: Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Transanal endoscopic microsurgery with entrance into the peritoneal cavity: is it safe?

BACKGROUND: Relative contraindications for transanal endoscopic microsurgery include high, anterior-based lesions for full-thickness excisions because of worries about entering the peritoneal cavity. Concerns exist regarding safety and oncological outcome. OBJECTIVE: We examined the outcomes of transanal endoscopic microsurgery excisions with entry into the peritoneal cavity and compared them with those that did not to address our hypothesis that entry is safe with no ill infectious or oncological consequences. DESIGN: This single-institution retrospective review uses a prospectively maintained database. SETTINGS: This study was conducted at a tertiary colorectal surgery referral center. PATIENTS: From 1997 to 2012, we identified 303 patients who underwent transanal endoscopic microsurgery resections, with 26 patients having entrance into the peritoneal cavity. MAIN OUTCOME MEASURES: Perioperative data, postoperative morbidities, delayed morbidities, and oncological outcomes were the primary outcomes measured. RESULTS: Of 26 patients, there were 8 women with a mean age of 67.5 years. Mean BMI was 31 kg/m, and ASA class was III or IV in 69%. Mean superior border of the lesion was 10.4 cm (4.5-16). Forty-eight percent had anterior-based lesions. Anterior location, level from anorectal ring, and diagnosis of cancer were significantly higher in the peritoneal entry group (p = 0.003, p = 0.007, and p = 0.007). Preoperative diagnoses included 16 adenocarcinomas, 8 polyps, and 2 carcinoid tumors. Thirteen patients had preoperative chemoradiation. Median estimated blood loss was 15 mL (5-400), and 3 patients underwent diversions. Median time to discharge was 3 days (2-10). There were no perioperative mortalities. Median follow-up time was 21.0 months. There was 1 local recurrence (3.8%), and there was no development of carcinomatosis. LIMITATIONS: This review was limited by its retrospective nature. CONCLUSIONS: High anterior location rectal lesions should be considered candidates for transanal endoscopic microsurgery excision in experienced hands. After obtaining considerable transanal endoscopic microsurgery experience, our use of transanal endoscopic microsurgery in a high-risk patient population allowed us to definitively treat 88% of patients without an abdominal operation and the need for a temporary or permanent colostomy. Theoretic concerns of abscess or carcinomatosis were not experienced (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A154).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: an emerging treatment option for advanced goblet cell tumors of the appendix.

BACKGROUND: The debate remains whether appendiceal goblet cell cancers behave as classical carcinoid or adenocarcinoma. Treatment options are unclear and reports of outcomes are scarce. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is considered optimal treatment for peritoneal involvement of other epithelial appendiceal tumors. METHODS: Prospective cohorts of patients treated for advanced appendiceal tumors from three peritoneal malignancy centres were collected (1994-2011). All patients underwent complete CRS+HIPEC, when possible, or tumor debulking. Demographic and outcome data for patients with goblet cell cancers were compared to patients with low- or high-grade epithelial appendiceal tumors treated during the same time period. RESULTS: Details on 45 goblet cell cancer patients were compared to 708 patients with epithelial appendix lesions. In the goblet cell group, 57.8 % were female, median age was 53 years, median peritoneal cancer index (PCI) was 24, and CRS+HIPEC was achieved in 71.1 %. These details were similar in patients with low- or high-grade epithelial tumors. Lymph nodes were involved in 52 % of goblet cell patients, similar to rates in high-grade cancers, but significantly higher than in low-grade lesions (6.4 %; p < 0.001). At 3 years, overall survival (OS) was 63.4 % for goblet cell patients, intermediate between that for high-grade (40.4-52.2 %) and low-grade (80.6 %) tumors. On multivariate analysis, tumor histology, PCI, and achievement of CRS+HIPEC were independently associated with OS. CONCLUSIONS: This data supports the concept that appendiceal goblet cell cancers behave more as high-grade adenocarcinomas than as low-grade lesions. These patients have reasonable long-term survival when treated using CRS+HIPEC, and this strategy should be considered.

Semiautomated segmentation for volumetric analysis of intratumoral ethiodol uptake and subsequent tumor necrosis after chemoembolization.

OBJECTIVE: Linear measurements, such as those described by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, may be limited for assessment of response after transarterial chemoembolization (TACE). The purpose of this pilot study was to show intra- and interobserver reproducibility of volumetric measurements of Ethiodol (ethiodized oil) seen within tumor 24 hours after TACE and of necrotic and viable tumor 1 month after treatment. Volumetric measurements are compared with linear measurements and survival outcomes. MATERIALS AND METHODS: Between 2006 and 2009, 37 consecutive TACE procedures were performed in 27 patients with hepatic malignancies. CT images obtained 24 hours and 1 month after TACE were retrospectively analyzed. Three observers measured volumes twice. Intraoperator reproducibility was determined using Wilcoxon's signed rank test to assess whether the difference in each volumetric measurement approaches zero. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to determine interoperator reproducibility. Survival data were retrospectively obtained from the electronic medical record. RESULTS: Good intraobserver reproducibility and interobserver reproducibility (p > 0.05, ICC > 0.9, respectively) were shown for Ethiodol, whole tumor, and necrotic tumor volumes. The volume of Ethiodol correlated with subsequent necrotic tumor volume (p = 0.009), reduction in whole tumor volume (p = 0.004), and patient survival (p = 0.029). Kaplan-Meier curves suggest that Ethiodol accumulation in more than 50% of the tumor and a 10% or greater increase in the volume of necrotic tumor correlated with survival (p = 0.028 and 0.047, respectively). CONCLUSION: Semiautomated volumetric analysis can be performed with good intra- and interobserver reproducibility. The volume of Ethiodol accumulated in the tumor after TACE correlates with subsequent necrosis. These early measurements may predict survival outcomes.

An appendix carcinoid tumor in a patient with hereditary nonpolyposis colorectal cancer.

Gastrointestinal carcinoid tumors are often associated with other tumors, particularly colon adenocarcinomas; but the association between carcinoid tumors and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has not yet been explored. We report an unusual case of a 28-year-old woman with HNPCC who underwent surgery for a transverse colon adenocarcinoma in whom an appendix carcinoid tumor was incidentally found. To assess whether the carcinoid tumor displayed the characteristic molecular features of HNPCC tumors, we investigated the expression of mismatch-repair (MMR) proteins and microsatellite instability (MSI) status in both tumors. Both tumors demonstrated normal expression of the MMR proteins hMLH1, hMSH2, hMSH6, and hPMS2. Interestingly, the adenocarcinoma exhibited an MSI phenotype but the carcinoid tumor did not, indicating that these 2 tumors arose through different molecular pathways.

Results of treatment of primary liver cancer at Kaunas University of Medicine Hospital.

Though the results of treatment of primary liver cancer depend on many circumstances, the opportunity to perform a curative liver resection remains the main point in prognosis on survival. The aim of the study was to examine our first experience in the treatment of liver cancer. From 1996 to 2001 we observed 54 patients with liver cancer: 46 hepatocellular and 6 cholangiocellular carcinomas, 1 malignant carcinoid, and 1 carcinosarcoma. In presence of liver cirrhosis (21 patients, 38.8%) hepatic function was evaluated using Child Pugh classification. Lesions were multiple in 28 cases and single in 26 cases. Ten patients (18.5%) were radically resected, 12 patients (22.2%) were managed by laparotomy and biopsy, 2 by percutaneous ethanol injections, 1 by trans-ileocolic portal vein embolization + hepatic artery embolization. There were 7 deaths (28%) and 18 complications (72%) after the surgical treatment. The survival results of patients who underwent resection were better (median 240 days) compared with palliative treatment group (median 113.3 days); by Log-Rank test p=0.208. CONCLUSION. The use of liver resections in patients affected by single or monolateral liver cancer is effective and potentially radical treatment. Mortality and morbidity rate is high. Alternative therapies can be conveniently considered in case of multicentric Child B-C patients.

[Treatment of intraocular metastatic tumors]. / Leczenie wewnatrzgalkowych guzów przerzutowych.

PURPOSE: Analysis of the clinical picture of intraocular metastatic tumors and the results of the treatment with various methods. MATERIAL AND METHODS: Between 1994-1997 intraocular metastatic tumors were diagnosed in 14 patients (19 eyes). There were 13 females and 1 male, aged 28 to 69 years (average 50). The primary tumor in 8 patients developed in the breast, in 4 cases in the lungs, 1 in the brain, and 1 in the kidney. In all patients the primary tumor was excised, then chemotherapy was applied in 9 cases, radiotherapy in 3 cases, and hormonal treatment in 2 cases. In 7 patients the metastatic process concerned also other organs: bones, liver, lungs, hypophysis, and lymphatic glands. Metastases developed in 10 months to 11 years since the diagnosis and treatment of the primary tumor. Intraocular tumors were the most often located near the optic disc (8 cases), or near the macula (4 cases). There were usually flat tumors (in 12 cases < 5 mm in thickness), creamy white, sometimes with pigment clamping. In order, to confirm the diagnosis of the tumor, USG was always performed and in 8 cases fluorescein angiography. In all cases topical treatment was applied, which consisted of irradiation with ruthenium (106Ru) in 6 eyes (in 1 case two times), laser coagulation in 3 eyes, and thermotherapy (TTT) with diode laser in 4 eyes, combined treatment (106Ru + TTT) in 2 eyes, 106Ru and 125I brachytherapy in one eye. The dose of radiation for the apex of the tumor was 60-90 Gy (av. 65). The eyeball was enucleated in 3 patients, 4 patients received chemotherapy. 2 patients received hormonal therapy, applied together with the topical treatment. RESULTS: In the majority of cases (14 eyes), a flat scar or the significant decrease of the volume of the tumor was obtained. 8 patients died, two are currently observed, the remaining 4 do not come to the control examination, and there is no information as to their fate. CONCLUSIONS: Good results of the treatment encourage further application of brachy and thermotherapy in the treatment of intraocular metastatic tumors. It allows for the conservative treatment of the eyeball, and also useful visual acuity is retained often.

Hepatic artery embolization for control of symptoms, octreotide requirements, and tumor progression in metastatic carcinoid tumors.

Hepatic artery embolization (HAE) has been utilized for treatment of advanced hepatic carcinoid metastases, with promising symptom palliation and tumor control. Our institution employs transcatheter HAE using Lipiodol/Gelfoam for treatment of carcinoid hepatic metastases, and this report presents our experience with twenty-four patients, examining symptom control, quality-of-life, octreotide dependence, and tumor progression. Twenty-four (11 male, 13 female, mean age = 59.4 +/- 2.5 yr) patients with carcinoid and unresectable hepatic metastases, confirmed by urinary 5-hydroxyindole acetic acid (5-HIAA) measurement and biopsy, were treated with Lipiodol/Gelfoam HAE from 1993-2001. Median follow-up was 35.0 months. Before HAE, 14 patients (58.3%) had malignant carcinoid syndrome, with symptoms quantified using our previously reported Carcinoid Symptom Severity Score, and 13 patients (54.2%) required octreotide for symptom palliation. Following treatment, symptom severity, octreotide dose, and tumor response were measured. Asymptomatic patients did not develop symptoms or require following treatment. Hepatic metastases remained stable (n = 4) or decreased (n = 19) in 23 patients (95.8%). Mean pretreatment Symptom Severity Scores (3.8 +/- 0.2), decreased to 1.4 +/- 0.1 post-treatment (P < 0.00001), with 64.3% of patients becoming asymptomatic. Mean pretreatment octreotide dosages (679.6 +/- 73.0 microg/d), decreased to 262.9 +/- 92.7 microg/d (P = 0.0024) post-treatment, with 46.2% of patients discontinuing octreotide. There were no treatment-related serious complications or deaths. This study demonstrates that Lipiodol/Gelfoam HAE produces excellent control of malignant carcinoid syndrome, allowing patients to decrease or eliminate use of octreotide, while controlling hepatic tumor burden.

[Arterial lipiodol chemoembolization of a left liver metastasis through the right internal thoracic artery]. / Chimioembolisation artérielle lipiodolée d'une métastase du foie gauche via l'artère thoracique interne droite.

The purpose of this article is to illustrate the efficacy of the chemoembolization in patients with hypervascular metastases and to describe the post-embolization change in vascularization pattern. Unusual collaterals may develop following embolization. A 59-year-old woman, followed for unresectable small bowel carcinoid tumor since 1991, underwent successful chemoembolization of several liver metastases. Only one liver lesion, located in segment IV, showed interval increase in size. This lesion was supplied by the right internal mammary artery. A branch of the right internal mammary artery was catheterized using a microcatheter and embolization was performed using doxorubicine-Lipiodol (Adriblastine, Lipiodol) and gelfoam (Spongel). No complications occurred after the procedure. The right internal mammary artery should be considered as a possible source of collateral arterial supply to the liver and should be evaluated in patients with local progression of disease.

Hepatic artery embolotherapy of hepatic metastases from carcinoid tumors: value of using a mixture of cyanoacrylate and ethiodized oil.

OBJECTIVE: Transcatheter embolization of the hepatic arterial supply is a well-known palliative treatment of tumor deposits in the liver. We performed a prospective study to evaluate the use of a mixture of N-butyl-2-cyanoacrylate and ethiodized oil with which a permanent vascular occlusion can be obtained, as an embolizing agent for transcatheter hepatic artery embolization for treatment of carcinoid hepatic metastases. SUBJECTS AND METHODS: Six patients had clinical symptoms from hormonal release by carcinoid hepatic metastases as well as elevated levels of 5-hydroxyindole acetic acid (5-HIAA) in the urine. Unilobar sequential transcatheter embolization of both the hepatic artery and the segmental hepatic arteries of both lobes of the liver was performed with a mixture of N-butyl-2-cyanoacrylate and ethiodized oil. CT and CT arterial portography (CTAP) were done to assess hepatic metastases and were used to monitor follow-up. Each patient had three CTAP studies; the third CTAP, performed 3 months after complete arterial devascularization, was compared with the first CTAP to evaluate tumor size. CT studies were performed routinely every 3 months thereafter and were compared with the initial CT scan to evaluate further tumor regression or progression. Tumor decrease and biochemical and symptomatic response rates were defined according to World Health Organization criteria. All complications and side effects of the treatment were documented. RESULTS: All patients showed complete symptomatic relief after embolization. The previously elevated levels of 5-HIAA in the urine returned to normal in three patients and in the other three patients were reduced by a mean of 89% of preembolization values. A decrease in tumor size by more than 50% was demonstrable in one patient; in five patients, hepatic lesions decreased in size by 25-50%. No new sites of metastatic liver disease were demonstrable in any patient during follow-up. No deaths or serious complications were directly attributable to the embolization procedure. All patients are alive after 12, 17, 18, 19, 19, and 19 months (mean, 17.3 months), respectively, with permanent relief of symptoms so far. CONCLUSION: Transcatheter embolization of both the hepatic artery and the segmental hepatic arteries with a mixture of N-butyl-2-cyanoacrylate and ethiodized oil provided excellent palliation in patients with carcinoid hepatic metastases. Complete and long-lasting relief of symptoms, a significant decrease or normalization of levels of 5-HIAA in the urine, and a reduction of metastatic tumor in the liver seem most likely to be the effect of sustained ischemia obtained with this permanent embolizing agent.

Colon carcinoid tumors. A population-based study.

PURPOSE: The aim of our investigation was to evaluate the clinical presentation of patients with carcinoid tumors of the colon and to estimate the survival and potential prognostic factors of this tumor type. METHODS: A population-based study was performed using data from the Alberta Cancer Registry between 1964 and 1988 (inclusive). The clinical records and the pathologic material of eligible patients were reviewed. Survival was estimated both as crude survival and with the Kaplan-Meier method. RESULTS: During the 25-year study period (1964-1988), 36 true carcinoid tumors of the colon were diagnosed in Alberta. Carcinoids of the ileocecal region and of the rectum were excluded from the study. The average age at time of diagnosis was 68.4 years; there were 20 males and 16 females. Symptoms (abdominal pain, diarrhea, weakness, anorexia) occurred late in the course of the disease: 64 percent of the lesions were in Dukes D stage and 22 percent were Dukes C at diagnosis. Only one patient presented with a malignant carcinoid syndrome. Lesions occurred most frequently in the cecum (39 percent), followed by transverse and sigmoid colon. Most of the patients were managed surgically. The perioperative mortality rate was with 22 percent, which is quite high. The average size of the lesions was 5.8 (range, 2-10) cm, and most tumors (31/36) had invaded the pericolic fat. The most common immunohistochemical pattern was argentaffin/argyrophil negative and neuron-specific enolase positive. Two-year and five-year actuarial (Kaplan-Meier) survival was 34 percent and 26 percent, respectively. Survival for carcinoids of the colon was significantly lower compared with carcinoids of the rectum or appendix, and with colon adenocarcinomas. Size of the tumor and tumor invasion into the muscularis propria--the two major histopathologic prognostic factors for carcinoids of the gastrointestinal tract--were not found to influence survival significantly. Rather, tumor stage, histologic pattern, tumor differentiation, nuclear grade, and mitotic rate were found to significantly influence the survival rate. CONCLUSION: Carcinoid tumors of the colon are extremely rare tumors, diagnosed late in the course of the disease, and they carry a bad prognosis. Prognostic factors are tumor stage, histologic pattern, differentiation, nuclear grade, and mitotic rate of the tumor.

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

PURPOSE OF THE STUDY: To evaluate the effectiveness of chemoembolization of the liver with doxorubicin and iopamidol emulsified in ethiodized oil for the treatment of metastatic neuroendocrine tumors. PATIENTS AND METHODS: Twenty patients with hepatic islet cell or carcinoid metastases were treated with selected hepatic arterial embolization consisting of an emulsion of doxorubicin and iopamidol emulsified in ethiodol followed by Gelfoam powder embolization. Fifteen patients had failed intravenous chemotherapy. Two of the patients with carcinoid tumors had three embolizations over 4 and one 6 years earlier with gelatin sponge only. RESULTS: In 14 patients with hormonally active tumors, hormones secretion decreased 90% (range 69-98%) in 10 days with relief of symptoms in all patients. Average tumor size decrease was 84%. Average hospital stay was 8 days. Six patients are alive and asymptomatic at 14-33 months postembolization. Fourteen patients have died 2-16 months postembolization. Ten patients died 2-37 months postembolization from progressive liver disease. One of these patients was 103 months post-Gelfoam embolization and 13 months postchemoembolization. In 8 patients, the pancreas was the primary site: 5 were nonfunctioning islet cell carcinomas, 1 glucagonoma, 1 gastrinoma and 1 carcinoid. The primary site in 1 patient with carcinoid was the bronchus, and the primary site was unknown in 1 patient with gastrinoma. The remaining 4 patients died with liver disease under control from renal failure, peritonitis, carcinoid heart failure and generalized bone metastases. The response rate was 95% with median duration of response 8.5 months. The median survival was 24 months. CONCLUSION: Chemoembolization with doxorubicin and iopamidol emulsified in ethiodized oil is less morbid than embolization with particulate matter alone, is more convenient and less costly, and it is less morbid than the effects of systemic chemotherapy. The median survival, duration and response compare favorably with other reported therapies.