Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

BACKGROUND: PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. METHODS: Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. RESULTS: A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. CONCLUSIONS: In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Portal vein embolization following shotgun-pellet injuries to the abdomen.

Multiple missile emboli are rare. The most likely setting for their occurrence is multiple penetrating injuries from birdshot. Such is this case of this 26-year-old man with birdshot injuries to the torso penetrating the portal vein and embolizing to the liver, producing infarcts and death.

Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer.

BACKGROUND/AIMS: Since 1989, thirty-two patients with advanced, intra-abdominal pancreatic cancer were treated with regional chemotherapy in combination with extracorporeal hemofiltration. PATIENTS AND METHODS: Eleven patients had locally advanced, unresectable cancer, and ten had advanced disease with liver metastases. Three patients had developed liver metastases following a radical resection. One patient had an incomplete resection with local residual disease, and a second had developed a local recurrence after a radical resection. One patient had an unresectable cystadenocarcinoma. Five patients had failed prior systemic therapies for unresectable pancreatic cancer. The patients underwent 85 treatments with regional chemotherapy plus hemofiltration, an average of 2.7 treatments per patient. RESULTS: Of 21 patients treated primarily with regional chemotherapy plus hemofiltration, there were two complete responses (9%) and eight partial responses (38%), an overall total response rate of 47%. The average survival for patients with Stage II/III localized, unresectable disease is 13 months and that for Stage IV unresectable disease with liver metastases is 9 months. CONCLUSIONS: Patients with recurrent disease following a radical resection or having failed prior systemic therapies generally had no benefit from regional chemotherapy plus hemofiltration.

Regional chemotherapy for melanoma. A 35-year experience.

OBJECTIVE: The authors present their 35-year experience with intra-arterial chemotherapeutic regional perfusion of 1139 patients with melanomas, using an extracorporeal oxygenated circuit and heart-lung apparatus. SUMMARY BACKGROUND DATA: Intra-arterial chemotherapy produces improved responses in many tumors. By isolating and sustaining the area with extracorporeal oxygenated circulation, high doses can be delivered to the tumor area, limited only by local toxicity. Drug levels up to 10 times those achieved by systemic administration are obtained. METHODS: Techniques for hyperthermic perfusion were developed for limbs, pelvis, head, neck, and skin of the breast. Melphalan (Burroughs Wellcome, Research Triangle Park, NC) was used in 753 patients. Combinations with melphalan or other drugs were used in remaining cases at temperature of 38 to 40 C for 30 to 60 minutes. RESULTS: Chemotherapy perfusion followed by tumor excision or node dissection, was performed where indicated. The cumulative 10-year survival for patients with localized melanomas was 70%. For patients with local recurrences or satellites within 3 cm, survival was 61%. For those with regionally confined intransit tumors, survival was 30%; for those with regional node involvement, 38%; for those with intransit and nodal metastases, 16%; for those with distant metastases and perfusion--mainly to save functional limbs--survival was 7%. Multiple perfusions were performed in 158 patients with recurrent disease on 366 occasions. Patients with indolent regionally confined melanomas were benefited by prolongation of useful life. CONCLUSIONS: Safe perfusion techniques are available for most anatomic regions. Increased chemotherapeutic doses are delivered to isolated areas limited only by local toxicity. Adjunct perfusion in poor prognosis stage I cases is useful in reducing local recurrence, and intransit or lymph node metastases. Regional perfusion reduces the need for major amputation. Multiple perfusion can be useful in treating recurrent chronic melanoma.

Fatty acid composition of erythrocytes and plasma triglyceride and cardiovascular risk in Asian diabetic patients.

The excess of coronary heart disease in Indian Asians compared with Europeans is unexplained by conventional risk factors, although the high prevalence of diabetes may play a part. To explore the contribution of diet we compared the fatty acid composition of erythrocyte membrane phospholipid and plasma triglyceride in 36 Gujarati Asians and 24 Europeans with non-insulin-dependent diabetes. Erythrocytes from Asian subjects contained higher proportions of linoleic, dihomogammalinolenic, and arachidonic acids, and lower proportions of oleic and n-3 series fatty acids; triglycerides contained higher linoleic and lower oleic acid levels. For example, mean percentage (SE) of oleic acid (18:1n-9) in erythrocytes was 16.7 (0.2) in Asians and 20.5 (0.6) in Europeans (p = 0.0001), and total n-6:n-3 ratio was, respectively, 12.8 (0.7) and 6.7 (0.7) (p = 0.0001). A high dietary intake of linoleic acid may not be cardioprotective unless balanced by significant intakes of oleic and n-3 series fatty acids, at least in diabetic Indian Asians. By itself, the conventional recommendation to substitute polyunsaturated for saturated fat in the diet may be inadequate to reduce thrombogenesis, and the overall balance of fatty acids, including monounsaturates, should be considered.

Multiple perfusions for melanoma.

From 1957 to 1992, 1139 patients had regional perfusion alone, or combined with excisional surgery for malignant melanoma. Of these, 158 patients had multiple perfusions for recurrent disease, including 155 for limb melanoma and three for head and neck melanoma. One-hundred-and-twenty patients were perfused twice, 28 treated three times, eight treated four times, and two treated five times. At first perfusion, 39 patients were classified as disease stages I and II, 98 at stage III, and 21 at stage IV. Melphalan was used in 70% of perfusions, either alone or in combination. Nitrogen mustard was used sparingly in only a few patients. Fifty-one patients with stage III disease had the greatest number of perfusions (127). Cumulative survival from date of first perfusion at 5 and 10 years were: stage 1,68 and 36%; stage IIIA, 25 and 16%; stage IIIB, 32 and 10%; stage IIIAB, 29 and 11% and stage IV, 14 and 0%. When compared with the entire series, the percent survival was decreased by 2 to 3 times, however, 21 patients remain alive and disease-free. For stages I and II, patients are alive and disease-free from 5 to 33 years. For stage IIIA, 6 patients were alive at the last follow-up, however, the status of two are currently unknown. For stage IIIB survival times range from 8 to 106 months with two patients alive without recurrence. For stage IIIAB, two patients are alive and disease-free at 15 and 26 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic evaluation of intracranial metastasis in malignant melanoma.

BACKGROUND: Malignant melanoma (MM) is often reported as the third most common cause of intracranial metastasis (IM) after carcinoma of the breast and lung. Most patients with advanced MM will have widespread extracranial disease, but the majority will die from intracerebral spread. METHODS: A retrospective review of 117 patients with documented IM from MM over the past 25 years was undertaken. Various factors (including age, race, sex distribution, primary lesions with Clark's level, Breslow's thickness, primary sites and staging at initial presentation, diagnosis of IM and its various treatment methods, survival data, and autopsy findings) were analyzed. Prognostic indicators were clarified from this analysis as a predictor of central nervous system (CNS) metastasis. An ideal treatment plan was also analyzed in order to predict a better survival. RESULTS: Fifty-eight percent of patients were male; 42% were female. Seventy-one percent of the primary lesions were of Clark's level IV and V, with mean Breslow's thickness of 3.5 mm. Median time interval between the initial diagnosis and development of IM was 3.5 years. Complete surgical resection of the intracranial lesion in the brain resulted in the longest mean survival of 10.3 months, whereas mean survival for the group with no treatment was only 3 weeks. Patients with primary lesions of the head and neck had the lowest mean survival of 3.3 months, whereas those whose primary sites were unknown had the longest mean survival of 7.5 months. One- and 2-year survival were 9% and 3%, respectively. All but one of the 30 patients at autopsy were found to have visceral metastasis, namely of the lung, liver, and bone. CONCLUSION: An aggressive search for metastasis should be undertaken in patients at high risk of developing CNS metastasis, e.g., male, head and neck primary, Clark's level IV and V, Breslow's thickness of > 3 mm, and presence of visceral metastases, mainly lung. A complete surgical resection should be attempted whenever possible, with adjunctive use of whole-brain irradiation, along with systemic chemotherapy for further control of recurrence and to prolong survival.

Gunshot injuries in Mobile County, Alabama: 1985-1987.

Although much information about firearm fatalities has been published, few articles have characterized all types of gunshot victims, the weapons used, and the injuries sustained in a well-defined geopolitical unit. This study of 597 persons sustaining gunshot injuries serious enough to cause death or hospitalization in Mobile County Alabama during 1985-1987, addresses that deficit. The overall rate of these 597 seriously gunshot-injured victims was 53/100,000 population per annum. Of the 597 victims, 215 died, resulting in a rate of 18.9 per 100,000 population per annum. Demographic characteristics of the homicide victims, predominantly young black men, and the suicide victims, predominantly middle-aged and elderly white men, are similar to those reported from other parts of the country. Assault victims accounted for the largest (316) number of victims: again, young black men also constituted the largest demographic group among assault victims. Handguns accounted for 71% of the weapons used. No assault type weapons were employed. Head, neck, and chest wounds led with the greatest fatality rates. Information about nonfatally wounded victims, particularly data about the weapons, proved difficult to obtain. This was one of the many problems encountered in this type of project and, consequently, is discussed at some length. Additional population-based studies using prospective methods and a variety of investigators, including persons knowledgeable of firearms, are needed.

Acral lentiginous melanoma.

Between 1958 and 1990, 82 patients with acral lentiginous melanoma were treated by the Tulane Surgical Service with regional perfusion, excision of lesion, and lymph node dissection. The patient group comprised 27 white men, 29 white women, 18 black men, and 8 black women, with an average age of 61 years. More foot lesions than hand lesions were reported, and all the lack men had foot lesions. In stage I patients, overall 5-year survival rates were 65% at 5 years and 44% at 10 years, with differences by race and gender. The black men did poorest, with a 13% 10-year survival rate. Survival rates were worse with increasing disease stage when calculated using univariate analysis. The 5-year survival rate of all patients with stage III and stage IV disease was 26%. A multivariate analysis was performed in 78 of 82 patients in whom all variables of Clark's level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clark's level, with stage of marginal significance. In a multivariate analysis of patients with stage I disease, an increasing level of invasion was found to be significant, with a trend for a relationship to thickness. A trend toward decreased survival time was observed in men and blacks.

Vaginal melanoma and the role of regional chemotherapy.

Vaginal melanoma is a rare cancer usually diagnosed as a locally advanced disease. Aggressive surgical management of the primary tumor and local-regional recurrences, combined with the use of adjuvant radiation and chemotherapy, improves disease-free interval and, perhaps, survival times. Techniques of regional chemotherapy allow the delivery of high doses of chemotherapy to the tumor bed, while minimizing systemic toxicities. These treatments can be used to decrease tumor size, render bulky tumors resectable, and decrease the need for radical procedures. Additionally, they may help eradicate clinically inapparent local-regional disease and have a favorable effect on survival times.

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.

Primary lymphoma of the penis with rationale of treatment.

Appropriate care of a patient with primary lymphoma of the penis requires consideration of the diagnoses, thorough evaluation, and knowledge of the various therapeutic approaches. A patient is presented with brief review of similar cases together with the rationale for the use of radiation therapy and chemotherapy rather than surgery.

Treatment of abdominal malignant neoplasms using regional chemotherapy with hemofiltration.

The regional delivery of high-dose chemotherapy for malignant neoplasms of the limb with the isolated regional perfusion technique was first described in the late 1950s. Recently, the use of concomitant hemofiltration for rapid systemic drug removal permits the use of higher regional drug levels in treating patients with advanced abdominal malignant neoplasms without complete vascular isolation. Twenty-five patients successfully underwent 42 treatments of high-dose intra-arterial chemotherapy with concomitant hemofiltration at Tulane University Medical Center Hospital, New Orleans, La, from 1989 through 1990. One patient (4%) achieved a complete response. Two patients (8%) had partial responses following high-dose intra-arterial chemotherapy with concomitant hemofiltration and their residual disease was resected for cure. Seven patients (28%) achieved a partial response, 11 (44%) had stable disease, and four (16%) had progression of disease.

Commentary on the Louisiana Cancer and Lung Trust Fund Board.

The Louisiana Cancer and Lung Trust Fund Board is pleased to have an agreement with this Journal to report on the accomplishments achieved in prevention, detection, and treatment of cancer and lung diseases. Several papers in this issue attest to the work being done in these areas.

Regional perfusion for the treatment of subungual melanoma.

Thirty-one patients with subungual melanoma representing 2.6 per cent of all patients with limb melanoma were treated by isolated regional perfusion. Acral lentiginous melanoma prevalent on subungual and volar skin was the most common histologic type. The subungual lesions primarily occurred on the lower limbs (61%) and great toe (48%). At diagnosis, most patients had advanced disease; 53 per cent of stage I patients had lesions with level IV invasion or greater. The median thickness of the primary lesion was 2.35 mm. All patients were treated by isolated regional perfusion and amputation of the involved digit, as well as regional lymph-node dissection where clinically indicated. The mean survival rate for all stages at five years was 35 per cent. Patients with stage I disease had the best survival rates, 61 per cent at five years and 54 per cent at ten years; however, patients with advanced disease, stage III (M.D. Anderson classification), had only a 17 per cent survival rate at five years and 8 per cent at 10 years. Women had slightly better survival rates than men, and patients with upper-limb lesions had the better prognosis.

Isolated regional perfusion for treatment of limb melanoma in the American black.

Since 1957, 961 patients with invasive malignant melanoma of the limbs were treated by regional perfusion. Forty-eight patients were black, representing 5 per cent of all patients with regional melanoma treated during this period. Thirty-one of the 48 patients were men, and 17 were women. Only 21 of the 48 patients had stage I lesions (M.D. Anderson classification), of whom 63 per cent had level IV or greater invasion. The average depth of invasion was 3.70 mm. Of 21 patients with stage III disease, 15 came to diagnosis with an intact primary lesion in addition to regional disease, and the majority of lesions arose on a plantar site with level V invasion. Eighty per cent of the patients had acral lentiginous melanoma. All melanoma patients were treated by isolated regional perfusion with wide excision of the primary plus regional lymph node dissection for biopsy-proven regional disease. At 10 years, survival rates were 71 per cent for stage I patients and 12.5 per cent for those with stage III disease. When black patients having had acral melanoma on a plantar or palmar site were compared with white patients of a similar stage of disease, however, it was found that black patients had equivalent long-term survival rates.