Human peripheral lymph lipoproteins are enriched in sphingomyelin.

The concentrations of total choline-containing phospholipids and of sphingomyelin have been determined in peripheral lymph from six volunteers. The concentration in lymph of total phospholipids was 14.6 +/- 6.0 mg/dl and of sphingomyelin 6.1 +/- 2.7 mg/dl; the estimated concentration of phosphatidylcholine (by subtracting the concentration of sphingomyelin from that of total choline-containing lipoproteins) was 8.5 +/- 5.1 mg/dl. The concentration of free choline in lymph was less than 1 mg/dl. The ratio of the concentration in lymph to that in the subject's own plasma of sphingomyelin was 0.18 +/- 0.07 and that of (estimated) phosphatidylcholine 0.05 + 0.04; the difference between these two ratios was significant at P less than 0.002. The present data are compatible with the hypothesis that some of lipoprotein phosphatidylcholine is lost while crossing from plasma to lymph.

Hepatic intra-arterial infusion of vincristine.

Currently the chemotherapeutic agents available for intra-arterial infusion in metastatic liver cancer are limited to only a few. The recent demonstration of the feasibility of prolonged IV infusion of vincristine led to exploration of hepatic intra-arterial infusion of this agent. A continuous infusion of 0.4 mg total dose was administered daily for 5 days via a hepatic artery catheter to each of six patients with metastatic liver cancer. Transient but life-threatening toxicity principally involving the nervous and gastrointestinal systems occurred in five of them. Future investigation of hepatic intra-arterial infusion of vincristine should be based on dose-schedules other than that employed in the current trial.

Continuous intravenous infusion of vinca alkaloid using a subcutaneously implanted pump in a canine model.

A major drawback of infusions of the vinca alkaloids is the lengthy period of hospitalization which is often required for this novel technique of cancer therapy. A potentially useful system to deliver outpatient therapy has been investigated in a preclinical study. A self-contained infusion pump powered by a self-charging fluorocarbon system has been implanted SC in three dogs. The performance of two pumps which had been factory-calibrated to deliver 2.5 and 4.5 ml/day, respectively, was evaluated during 22 infusions of the vinca alkaloids (vincristine, 7; vinblastine, 7; and vindesine, 8). Infusions were given over a 5- to 7-day period and were repeated at 3-week intervals. No malfunctioning of the pumps occurred in over 500 cumulative days of use. The flow rates of the pumps were quite stable except in one animal whose increased flow rate was probably a consequence of fever due to self-induced inflammation about the pump pocket. No local or distant tissue reactions to the pump were observed. Decomposition of vincristine and vinblastine in the infusate at the end of 5- or 7-day infusions was minimal as determined by high-pressure liquid chromatography. The amount of decomposition of vindesine in the infusate was variable. Steady-state concentrations of vincristine during infusion were always greater than 10(-9) M, and were similar to those previously determined in our clinical infusion trials using a dosage of 0.5 mg/m2/day. Clinical evaluation of this system for prolonged infusions of vincristine and other vinca alkaloids appears to be warranted.

Colon and rectal carcinoma. Forty years and 1400 cases.

One thousand four hundred cases of colorectal carcinoma were treated primarily at the Wake Forest University Medical Center between 1945 and 1985. The surgical approach was constant in all patients without obvious stage IV disease: wide resection, including at least the primary-level and intermediate-level lymph nodes. There were 812 women and 588 men in the series. Sixty-eight per cent of the 1400 cancers occurred in the rectosigmoid, but only 53 per cent of the last 300 cases were in this region. Initial staging showed 560 cases (40%) of local disease, 504 cases (36%) of regional disease, and 336 cases (24%) of distant disease. Cecal, ascending, hepatic, and transverse lesions were most often associated with stage IV disease. Among the 1115 patients with long-term follow-up, 44 per cent with stage I disease, 37 per cent with stage II disease, 24 per cent with stage III disease, and 6 per cent with stage IV disease had survived for 5 years or longer. There were no differences when 5-year survival was correlated with site. This review provided no evidence that wide resection leads to increased long-term survival.

The risk of improperly staging Hodgkin's disease with partial splenectomy.

Partial splenectomy has been proposed for staging Hodgkin's disease, but the risk of thereby missing limited splenic involvement is unknown. To assess that risk, we reviewed all spleens removed during staging laparotomies for Hodgkin's disease at our institution, assessing splenic weight, the characteristics of all nodules, and grossly visible subcapsular disease. Among 180 spleens, 65 had splenic disease. Fifty-three had six or more nodules; for 49 of those, other abdominal involvement had been present or the disease was so diffuse that staging by partial splenectomy would have been correct. The remaining 12 spleens (18%) contained five or fewer nodules. Eleven had no grossly visible subcapsular nodules, and five of the 11 were associated with no other abdominal involvement. In four of those five, the disease was localized to one area in such a way that it could have been missed by partial splenectomy. All positive spleens averaged 415 g; the four spleens with localized involvement averaged 287 g. Thus, in four of 65 patients, a few splenic nodules in a localized distribution not visible grossly were the only evidence of abdominal Hodgkin's disease, and if partial splenectomy had been done there would have been a 6.2 per cent risk of understaging their Hodgkin's disease.

Pseudocalculus sign. A pitfall of static cholangiography.

The pseudocalculus formation was first noted by Caroli in 1960, and was first called a sign by Beneventano and Schein in 1968. It is a cholangiographic illusion that appears as a filling defect in the distal common bile duct when static or "spot" films are exposed during the contractile phase of choledochal sphincter activity. Although first noted and most frequently seen in T-tube cholangiography, it is seen also during intravenous and intraoperative cholangiography. Because it mimics radiographically an impacted stone in the distal common bile duct, its delineation is critical to avoid unnecessary instrumentation of the common bile duct or even reoperation. In this review the authors discuss briefly the anatomy and physiology of the distal common bile duct and the etiology, differential diagnosis, and recognition of the pseudocalculus sign.

Postmastectomy angiosarcoma.

Six cases of postmastectomy angiosarcoma of the upper extremity have been treated at the North Carolina Baptist Hospital/Wake Forest University Medical Center over the past 25 years. Five patients had typical ductal carcinoma; one patient had mammary Paget's disease. Two patients, including the patient with Paget's disease, had bilateral mastectomies. The five patients with ductal carcinoma had received postoperative radiation therapy. The mean interval between mastectomy and the appearance of angiosarcoma was 17.5 years. Significant lymphedema of the upper extremity preceded the appearance of angiosarcoma in all six patients, and it appears important that special care be taken during mastectomy to preserve the integrity of the lymphatic system. The patient treated with interscapulothoracic amputation is alive at 2 years postamputation; the five patients whose angiosarcomas were treated with wide excision or radiotherapy died an average of 4.5 years later. Interscapulothoracic amputation is recommended as the initial treatment of postmastectomy angiosarcoma of the upper extremity.

Evaluation of technique for autotransplantation of the spleen in dogs.

Preservation of the human spleen is important in the prevention of overwhelming sepsis, particularly in infants and immunosuppressed patients. When that preservation is not possible, due to disease or severe trauma, it has been suggested that autotransplantation of splenic tissue might provide adequate immunological protection. This study looked at the feasibility of autotransplantation via subcutaneous implantation in the dog. This method is important, since controlled intraabdominal splenosis is very difficult to achieve. The adverse effect of splenectomy, as well as the ineffectiveness of autotransplantation was demonstrated in providing demonstrable in vitro evidence of decreased sheep red blood cell immunization, even though the subcutaneous implantation itself was successful. From this study, the authors suspected, but could not prove, that the ineffectiveness of the splenic autotransplants was related to their lack of critical mass for good bacterial clearance from the blood stream and the fact that they did not lie within the main vascular channels, probably a criterion for proper clearance. The role of splenic preservation by autotransplantation needs to be evaluated in the immature host.

Screening for colorectal cancer.

A voluntary colorectal screening program was carried out in North Carolina to evaluate the public's willingness to perform a do-it-yourself bowel test, to educate the public on the importance of routine colorectal screening, and to assess the efficacy of a small-scale screening program in detecting colorectal cancer. A screening kit was requested by 1,204 individuals after hearing or reading about the program; 770 kits were returned. Of 29 (3.7%) positive test results, six were negative after retesting. Adequate follow-up was available for 18 of the remaining 23 positive results. Thirteen were due to anal bleeding, diverticulosis, or heavy ingestion of aspirin; five were considered false-positive results, since no evidence of disease could be found. No cases of polypoid tumors or carcinoma were detected. The main value of such a program in an area with a small population base is to increase the awareness of the public of the importance of routine screening for colorectal cancer.

Hepatic artery infusion for metastatic neoplastic disease.

Specific conclusions can be drawn concerning HAI in the treatment of neoplastic hepatic disease. Over-all, a rate of response of 50 per cent is noted, with the results of more recent studies showing improved response rates as measured by a CEA marker. There are extremely few, if any, complete responders. Nonresponders have one-half the survival time of responders. The median time of survival in patients who have received HAI is about one year. There have been series in which the mean survival rate is greater than that in historical control patients, but no one has demonstrated this fact with a matched group of patients in a prospective controlled trial; many such controlled trials are now underway. The duration of survival in patients receiving treatment is strongly influenced by the development and progression of extrahepatic lesions. Placing HAI catheters by laparotomy is more dangerous to life, but the morbidity is higher with percutaneous HAI. On the other hand, patients treated percutaneously have a much higher incidence of thrombosis of the hepatic artery and of other problems related to the catheter, including migration and dislodgment, so that treatment is compromised. The high numbers of patients treated by percutaneous therapy in the past who had an increased incidence of thrombosis of the hepatic artery perhaps have had some influence on the response rate. The technology of HAI has improved rapidly and markedly during the last several years with the development of such pumps with advanced design as the totally implantable, refillable and rechargeable infusion pump. What is needed now are studies designed to determine the best agent or combination of agents that can be administered through these advanced systems. Long term, controlled clinical trials of HAI in the ambulatory patient are underway, but the results are not yet available.

Staging laparotomy in Hodgkin's disease.

Staging laparotomy (multiple liver and lymph node biopsies and splenectomy) was performed at the North Carolina Baptist Hospital in 123 patients with Hodgkin's disease. There were no deaths. Wound, pulmonary, intra-abdominal or urinary tract complications developed in 17 patients. Of those complications, one case each of pelvic abscess, subphrenic abscess, small bowel obstruction, staphylococcal peritonitis and subphrenic hematoma required a major intra-abdominal operation. The patients were classified on the basis of histopathology; nodular sclerosis--40, mixed cellularity--44, lymphocyte predominant--24, lymphocyte depleted--13, and undetermined--2. The pathological stage following laparotomy was unchanged from the clinical stage in 62%, reduced in 15%, and advanced in 23%. Subsequent therapy, therefore, was altered in 38% of the patients. Lymphangiography, done in 108 patients, showed lymph node involvement in 46 patients and no involvement in 62 patients. Of those lymphangiographic findings, 79% were confirmed histopathologically, 19% were falsely positive, and 1.8% were falsely negative. There were positive findings of Hodgkin's disease in the spleen in 42% of patients. The staging laparotomy continues to be a valuable tool in the staging and treatment of Hodgkin's disease.

Primary leiomyosarcoma of the inferior vena cava: a case report and review of the literature.

Sixty-six cases of leiomyosarcoma of the inferior vena cava (IVC) have been reported. We present another case and review the characteristics and treatment of this rare tumor. IVC leiomyosarcomas spread by extension into adjacent tissue planes. Direct extension into the heart is known, but not into the kidneys, adrenals, or bowel. IVC leiomyosarcomas arising below the renal vein cause pain in the right-lower quadrant, back, and flank, and varying degrees of lower extremity edema; those arising in the middle caval segment cause right-upper-quadrant pain and sometimes renovascular hypertension; those arising above the hepatic vein cause varying manifestations of the Budd-Chiari syndrome. A reasonable approach to early diagnosis involves oral and intravenous contrast studies followed by computed tomography, angiography, and vena cavography. Aggressive surgical treatment is optimal in light of the tumor's slow growth pattern and relatively low malignant potential. (Metastases have been reported in fewer than 50% of cases). Tumors involving the lower IVC are most amenable to surgery; extensive collateral venous drainage of the left kidney preserves renal function during resection of middle caval tumors. Upper caval leiomyosarcomas are the least amenable to complete removal. Postoperative survival of all patients has ranged from a few weeks to eight years.

Gemfibrozil increases apolipoprotein A-I and cholesterol concentrations in human peripheral lymph.

Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18-60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A-I concentration of 30-108% (mean, 66%; P < 0.01), and in lymph cholesterol concentration of 35-100% (mean, 59%; P < 0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A-I concentration (mean, +7%) and plasma total cholesterol concentration (-7%) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood-endothelium interface increases the transfer of apo A-I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells.

Operative technique for insertion of a totally implantable system for venous access.

A totally implantable venous access device is described and a step by step technique for implanting the device is given. Among 203 patients in whom the technique has been used, thrombosis of the subclavian or jugular vein has occurred in only three. There have been no pulmonary complications, and only three devices have been removed because of infection.

Agenesis of the gallbladder--an inherited defect?

Agenesis of the gallbladder is a rare anomaly believed to be an organogenetic failure. This is the third instance of familial agenesis of the gallbladder reported in the literature. The diagnosis of agenesis of the gallbladder can only be made during exploratory celiotomy and must be confirmed by an intraoperative needle cholecystogram. This congenital anomaly should be suspected when oral cholecystography shows a nonvisualizing gallbladder in relatives of any patient with proven agenesis of the gallbladder.

A method of securing the arterial catheter for hepatic artery infusion.

The infusion of chemotherapeutic agents through the liver is an important part of the non-surgical treatment of metastatic carcinoma of the liver. A stable catheter position is essential to the maintenance of good hepatic infusion. This technique assures that stable position.

Cellular blue nevus simulating metastatic melanoma: report of an unusually large lesion associated with nevus-cell aggregates in regional lymph nodes.

A young Caucasian woman had a large area of blue-gray discoloration on the flank and palpable axillary lymph nodes. The discolored area had enlarged during a recent pregnancy, contained multiple subcutaneous nodules, demonstrated increased cellularity and mitotic activity, and was associated with an axillary lymph node containing black streaks within the capsule. Although the lesion was initially considered to be a metastatic malignant melanoma, re-evaluation showed it to be a benign cellular blue nevus with benign nevus-cell aggregates within a regional lymph node. We report this case to emphasize how cellular blue nevus can simulate malignant melanoma and to increase physician awareness of this benign variant of melanocytic nevus so that inappropriate surgery and chemotherapy can be avoided.