Increased adriamycin levels in hepatic implants of rabbit Vx-2 carcinoma from regional infusion.

Regional infusion chemotherapy for the treatment of primary or secondary hepatic cancer should allow delivery of a higher drug concentration to the tumor with decreased systemic exposure when compared with systemic therapy. Fifteen rabbits, each implanted with two hepatic Vx-2 tumors, were treated with infusion of Adriamycin (3 mg/kg and 7.5 muCi of [14C]Adriamycin) through the hepatic artery (n = 5), portal vein (n = 5), and a systemic vein (n = 5) at 20 mg/min. 99Tc-labeled macroaggregated albumin flow images documented specific hepatic perfusion in selected rabbits using this technique. Thirty min after infusion the animals were sacrificed, and multiple specimens of liver, tumor, and heart were taken for liquid scintillation counting and high-performance liquid chromatography. The 14C label remained associated with Adriamycin and metabolites. After systemic infusion 11.5 nmol/g of Adriamycin were found in tumor, and 32.4 nmol/g were found in liver. Infusion of Adriamycin through the hepatic artery produced drug levels of 34.3 nmol/g of tumor and 48.4 nmol/g of liver, while infusion through the portal vein produced drug levels of 6.5 nmol/g of tumor and 54.4 nmol/g of liver. The drug concentration in tumor was significantly higher after hepatic artery infusion compared with systemic (P less than 0.05) or portal vein (P less than 0.01) infusion. The tumor/liver ratio of [14C]Adriamycin tissue levels after hepatic artery infusion was greater than that measured after systemic vein treatment (no overlap of the 90% confidence intervals). Systemic infusion of Adriamycin produced a higher level of Adriamycin in the heart (13.6 nmol/g) than did hepatic artery (10.9 nmol/g) or portal vein (8.9 nmol/g) infusion. Hepatic artery infusion achieved the highest tumor Adriamycin level compared with systemic vein and portal vein infusion. The results suggest that these tumor implants are supplied primarily by the hepatic artery, that clearance of Adriamycin is efficient after regional infusion, and that systemic toxicity may be reduced using intraarterial infusion of Adriamycin for hepatic tumors.

Multi-purpose silastic dual-lumen central venous catheters for both collection and transplantation of hematopoietic progenitor cells.

Autologous peripheral blood progenitor cell (PBPC) transplantation frequently requires sequential placement and use of two separate central venous catheters: (1) a short-term, large-bore, stiff device inserted for leukapheresis, and after removal of that device, (2) a long-term, multi-lumen, flexible, Silastic catheter for administration of high-dose chemotherapy, re-infusion of hematopoietic cells, and intensive supportive care. We reviewed our recent experience with two dual-lumen, large-bore, Silastic multi-purpose ('hybrid') catheters, each of which can be used as a single device for both leukapheresis and long-term supportive care throughout the transplant process. Quinton-Raaf PermCath and Bard-Hickman hemodialysis/apheresis dual-lumen catheters were used as the sole venous access device in 112 consecutive patients who underwent autologous PBPC collection and transplantation. The catheter exit site was monitored three times a week, and lumen patency was assessed using clinical and radiologic techniques. Catheters were removed prematurely for persistent thrombus, positive blood cultures despite appropriate antibiotics, or mechanical dysfunction. There were no intra-operative or immediate post-operative complications relating to insertion. Thirty-two patients experienced catheter occlusion necessitating urokinase instillation. Persistent occlusive problems were noted in 16 patients, and in 10 patients the catheter had to be removed. Two exit site infections and 17 bacteremias occurred. Catheters had to be removed for persistent infection in two subjects and for mechanical problems in five others. Cost analysis comparing the hybrid catheters alone vs conventional devices revealed a charge of $4230 in patients with hybrid catheters vs. $7530 in those requiring a temporary non-Silastic dialysis catheter in addition to a flexible, long-term Silastic catheter. Hybrid, Silastic, dual-lumen, large-bore central venous catheters are safe, cost-effective and convenient multi-purpose venous access devices that may be used in the setting of autologous PBPC collection and transplantation. The rate of thrombotic, infectious and mechanical complications appears comparable to other central venous access devices.

Wound coverage by a sheet of epidermal cells grown in vitro from dispersed single cell preparations.

Epidermal cells have been grown into multilayered sheets resembling full-thickness human epidermis using a new tissue culture technique. To evaluate their viability in an in vivo situation, such cells were transplanted under the kidney capsule and into a subcutaneous position in the nude mouse. In both locations cells survived and limited growth was observed. Maturation of the epidermal cells resulted in the appearance of keratohyalin granules and cell desquamation. To assess the potential use of tissue cultured cells for wound treatment in man, the same method was used to grow dog cells in vitro. Sheets of multilayered dog epidermal cells grown in vitro from a single cell suspension were used to cover fresh or granulating wounds. The epidermal cells transplanted in this way remained viable and wound coverage was achieved within 1 week. No clinical or histological signs of rejection of allograft tissue were observed during a 6-week period of observation.

Virilizing hilus (Leydig) cell tumor of the ovary: the challenge of an accurate preoperative diagnosis.

A 73-year-old woman developed temporal balding and "hoarseness" over a 3-year interval. Investigation including extensive endocrinologic screening, abdominal computed tomography scanning, pelvic ultrasonography, iodocholesterol (NP-59) adrenal scanning, and selective retrograde venous sampling revealed only an elevated serum testosterone level without localization of the source. At laparotomy a 2.0 cm left ovary was found to contain a hilus (Leydig) cell tumor. The testosterone level in a blood sample from the left ovarian vein obtained intraoperatively was 9000 ng/dl, whereas a blood sample from the right ovarian vein contained 213 ng/dl. One week later her peripheral blood testosterone level was normal (8 ng/dl). The records of six other patients with ovarian hilus cell tumors were reviewed from the Memorial Hospital Registry (from 1959 to 1982). All tumors were small (ovaries were 2 to 4 cm in diameter) and benign. The average patient's age was 63 years (range: 57 to 73 years). Only three of the seven patients in our series were first seen with virilization; the tumors in the remaining four patients were found incidentally. Ovarian hilus cell tumors are rare and are difficult to diagnose, but surgeons and endocrinologists should think of this tumor when they investigate older female patients with virilization. Careful intraoperative examination of even normal-appearing ovaries is imperative, particularly if no adrenal disease is found.

Aspergillus-induced small bowel obstruction in a leukemic newborn.

An infant with congenital acute myelocytic leukemia, who was being treated with chemotherapeutic agents, developed obstruction and infarction of the ileum due to occlusion of mesenteric arteries by Aspergillus hyphae. This case demonstrates how blood vessel occlusion by occult aspergillosis can present clinically as a surgical emergency.

Aneurysm of the gastroduodenal artery: an unusual cause of obstructive jaundice.

Splanchnic artery aneurysms are among the most infrequent aneurysms that affect the arterial circulation. Aneurysms of the gastroduodenal artery are the rarest splanchnic artery aneurysms, comprising fewer than 10 per cent of all such lesions. The most typical presentations include abdominal pain and acute gastrointestinal bleeding. However, the diagnosis is often missed preoperatively. We report the successful surgical management of a patient with a gastroduodenal artery aneurysm who presented with isolated obstructive jaundice and review the literature on this unusual finding.

Fatal mediastinal abscess from upper respiratory infection.

Suppurative mediastinitis following neck infection is an uncommon entity that carries a 40% mortality. It is most commonly associated with esophageal perforation or odontogenic abscess. The rapidity of spread has been attributed to dependent drainage from the neck into the mediastinum, negative intrathoracic pressure, and synergistic necrotizing bacterial growth. Cultures obtained usually grow streptococci and/or Bacteroides. We report the case of a 34-year-old woman with an upper respiratory infection who subsequently was found to have a para-/retropharyngeal and mediastinal abscess. Septic shock, respiratory failure, and death ensued, despite aggressive treatment with broad-spectrum antibiotics (for both aerobes and anaerobes), surgical drainage of the neck and mediastinum, and cardiorespiratory support. The danger of a rapid downhill clinical course with mortality due to suppurative mediastinitis makes early diagnosis of critical importance. All clinicians evaluating a "sore throat" should consider neck edema or gas on neck radiograms as evidence of cervical abscess, and subsequent widening of the mediastinum on chest x-ray as an ominous sign suggesting mediastinal abscess.

Administration of chemotherapeutic agents. Techniques and controversies.

Safe and pain-free vascular access is now the achievable goal for every patient receiving systemic chemotherapy. The discomfort and anxiety that used to accompany multiple (often unsuccessful) venipunctures can be avoided by placement of a long-term central-venous-access device as part of the patient's early treatment plan. In the United States, approximately 5 x 10(5) such devices are now inserted each year. This review discusses and compares the different types of devices currently available, methods of insertion, and management of morbidity. Future studies should focus on the cost effectiveness of these devices, better selection of patients for the various types of access, and avoidance, recognition, and treatment of complications.

Vascular access grafts for chemotherapy. Use in forty patients at M. D. Anderson Hospital.

Forty-two arteriovenous grafts were placed to provide vascular access in 40 patients with poor or sclerosed superficial veins. Thirty-nine patients had malignant disease and required chemotherapy, while one patient with aplastic anemia needed frequent transfusions. Thirty-two grafts were placed in the arm (27 straight and 5 loop), and ten in the leg (femoral-femoral loop). Thirty-seven shunts consisted of 6 mm polytetrafluoroethylene (PTFE), and five were 6 mm Dacron((R)). The straight brachial artery to axillary vein PTFE graft was preferred, while the PTFE femoral loop graft was a satisfactory alternative. The loop arm graft was associated with a high complication rate and is no longer used. Local anesthesia was employed in all cases except for a 3-year-old child. There was no operative mortality and no severe morbidity, despite subsequent myelosuppression by chemotherapeutic agents injected via these grafts. Thirty patients are alive, while ten died of their malignancy. Twenty-six grafts are functional and have been in place an average 4.4 months (range: 1 to 14 mo.). Acceptance by patients and particularly by personnel in the out-patient chemotherapy unit has been enthusiastic. Vascular access grafts can be inserted safely and provide a convenient route for drawing blood samples, and for administering chemotherapy and intermittent intravenous therapy in selected patients with neoplastic disease.

Results from use of 826 vascular access devices in cancer patients.

Vascular access technology is rapidly improving. Over the last 7 years we evaluated 826 access devices in 681 patients with neoplastic disease. The devices included 103 polytetrafluoroethylene (PTFE) arteriovenous (A-V) grafts, 358 Broviac 2.2-mm and 135 Hickman 3.2-mm right atrial catheters, 161 2.2-mm and 44 4.5-mm dual-lumen right atrial catheters, 12 venous infusion ports, and 13 large-bore staggered-tip dual-lumen catheters. All devices provided satisfactory venous access. Twenty-eight percent of the PTFE A-V grafts eventually thrombosed, versus 0.7% of Silastic right atrial catheters (P less than 0.005). Because of its low long-term complication rate (only 7% removed or lost because of a complication) and its simplicity of insertion and use, the Silastic right atrial catheter is now our preferred device. Most patients receive a 2.2-mm dual-lumen catheter, the second channel of which can provide a route for parenteral nutrition or blood sampling, and is a form of "insurance" if the first lumen becomes occluded. In over 95% of patients with chemotherapy-induced neutropenia and fever or bacteremia, their right atrial catheters were not removed, rather they were used for intravenous antibiotic infusions. The new larger bore dual-lumen catheters provided effective access for acute hemodialysis or plasmapheresis, as well as for routine venous access. The infusion port was particularly suitable for administration of adjuvant chemotherapy in the outpatient department, although the complexity of its use challenged the professional staff.

Two Broviac catheters for intensive long term support of patients with cancer.

Two Broviac catheters were placed simultaneously in 93 patients who required prolonged intravenous support while receiving chemotherapy or a bone marrow transplant. The technique involved two venotomies in a single vein and was performed under local anesthesia in the operating room. Pancytopenia was not considered a contraindication. Blood sampling and intensive treatment with blood products, chemotherapy, parenteral nutrition and multiple antibiotics were facilitated by these durable, well-tolerated Silastic catheters. Patients were taught to care for them following discharge, and the majority of catheters were used for outpatient treatment. The few complications encountered were compensated for by the convenience and safety of the double Broviac method. The danger of chemotherapy extravasation was completely obviated, as were the complications of repeated central line insertion, and the anxiety and pain associated with multiple unsuccessful attempts at venipuncture. Because of the enthusiastic acceptance of long term Silastic catheters by patients and nursing staff, we regard this technique was a step forward in solving the problem of difficult vascular access in cancer patients.

Open insertion of right atrial catheters through the jugular veins.

A safe and effective method for placement of all types of long term Silastic right atrial catheters into the central veins by open cutdown is described. The certainty that the catheter can be passed in this way through either the external or internal jugular vein, using only one incision, allows the procedure to proceed smoothly and without interruption. Percutaneous attempts that have a higher complication rate and cephalic vein cut-downs that are unsuccessful because of inadequate vein caliber are thereby avoided.

Sarcomas related to the heart and vasculature.

Soft tissue sarcoma is the most common malignant neoplasm of the heart, pericardium, and great vessels. Its presentation is infrequent, nonspecific, and subtle. For example, emboli from these tumors to the lungs or peripheral arteries may mimic thrombotic embolic disease. New noninvasive techniques such as echocardiography and magnetic resonance imaging (MRI) aid in diagnosis and preoperative assessment. Angiosarcoma, the most common cardiac sarcoma, is aggressive and usually arises in the right atrium. Kaposi's sarcoma of the heart has been found in patients with AIDS and in immunosuppressed organ transplant recipients. Most primary sarcomas of the aorta and pulmonary artery (the elastic arteries) show minimal differentiation and are classified as "intimal, sarcomas," whereas leiomyosarcomas predominate in the muscular arteries and great veins. Surgical resection of any sarcoma of the vasculature, when feasible, is technically challenging but may result in cure or palliation. Adjuvant chemotherapy and radiation therapy can also relieve symptoms and prolong survival.

Palliation of malignant ascites by the LeVeen peritoneo-venous shunt.

A LeVeen peritoneo-venous shunt was placed in each of 5 patients under local anesthesia to relieve symptomatic malignant ascites. All patients had marked ascites due to histologically documented intraabdominal carcinomatosis, extensive hepatic neoplasm, or a combination of malignant ascites and severe parenchymal liver disease. Cases included metastatic breast carcinoma, pancreatic carcinoma, melanoma, and primary cholangiocarcinoma. Prompt relief of respiratory distress and discomfort associated with tense ascites was achieved in all patients; however, survival was short (one week to seven months) due to advanced disease. The LeVeen shunt can provide effective palliation of malignant ascites in carefully selected symptomatic patients.

Atherosclerotic coarctation of the abdominal aorta in women.

In the ten year interval from 1967 to 1976, in a group of 200 patients with aortoiliac occlusive disease, six were identified who presented a unique combination of physical findings, angiographic abnormalities and pathologic changes. Atherosclerotic coarctation describes this entity because of the discreteness of the lesion found, the extent to which the aorta is occluded and the presence of extensive collaterals. Pathologically, the lesion is an organized thrombus forming on a single ulcerated plaque in an aorta with a lumen that is otherwise well preserved. Distally, infantile vessels are found. Other features have been the absence of diabetes mellitus and the fact that all of these patients have been women. All but one patient smoked cigarettes. Local endarterectomy restored pedal pulses and provided lasting relief of symptoms in all of the patients.