Use of isotopic immunoglobulin in therapy.

Antibodies raised in heterologous species against tumor-associated antigens such as ferritin and carcinoembryonic antigen may be utilized in diagnostic scanning and in cancer therapy. The radiolabeled (131I) antibodies have a mean effective half-life of 3 days. The tumor-bearing regions retain activity which was associated with objective evidence of remission in primary hepatic cancers. Major organ toxicity was not apparent in eight of nine patients treated with radioactive antibody. Objective evidence of clinical remission was documented by computer-assisted axial tomography scan remission in sequential studies that determine residual tumor in the same planar cuts. Future possible improvements in radioimmunoglobulin are discussed in light of the clinical findings.

The role of computed tomography of the chest in the management of small-cell lung cancer.

Despite the wide application of computed tomography (CT) in the diagnosis and management of lung cancer, the role of this diagnostic modality in the management of small-cell lung cancer (SCC) has not yet been defined. We therefore compared information gained from routine chest radiography (CXR) and CT scans performed on 32 patients with SCC who were treated on an intensive chemotherapy-radiotherapy protocol. Seventy-nine pairs of CXRs and CT scans were retrospectively reviewed. We found that although CT delineates a greater extent of intrathoracic disease in each of nine anatomic areas evaluated than does CXR, agreement between CT and CXR was significant for all areas except the pericardium. Pericardial thickening was seen only on CT scan and is more frequent in SCC patients than has previously been appreciated, but both its etiology and prognostic significance are unclear at this time. CT also allowed interpretation of disease status in cases where radiation-induced fibrosis made interpretation of the CXR impossible. We do not recommend routine use of chest CT at time of diagnosis of SCC, but we recommend that its use be reserved for evaluation of new symptoms or suspected relapse, or when radiation fibrosis on CXR is severe.

Iodine 131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group study.

One hundred five patients with hepatoma were treated with iodine 131 antiferritin in three sequential protocols in phase 1-2 trials. Therapy began in all trials with external beam irradiation and chemotherapy. The dosimetric results with 131I antiferritin indicated that 30 mCi (8 to 10 mCi/mg immunoglobulin G [IgG]) was sufficient to saturate the tumor. Tumor-effective half-life of the radioactive antibody was 3 to 5 days and was dependent on the species of animal from which the antibody was derived. This led to a 30 mCi on day 0 and 20 mCi on day 5 treatment schedule. Toxicity was predominantly thrombocytopenia. Due to clinical remission, cyclic therapy was next developed with antibodies from different species of animals. Rabbit, pig, monkey, and bovine antibodies were determined to produce the longest tumor-effective half-life and therefore the highest dose of radiation. Integration of 15 mg doxorubicin and 500 mg 5-fluorouracil (5-FU) with 131I antiferritin was accomplished next. Remission to external beam radiation was evaluated by computed tomography (CT) scan tumor volume computations that indicated that 22% of the patients had a partial remission (PR) from initial presentation to 1 month following external irradiation and chemotherapy. From the time of radioactive antibody administration, 48% of the patients (7% complete response [CR] and 41% PR) achieved remission to 131I antiferritin. Of 79 patients evaluated by CT scan tumor volumetrics 50% of the patients (7% CR and 43% PR) remitted to the entire treatment regimen. Patients not previously treated and without metastasis who were alpha fetoprotein positive (AFP+) had a 5-month median survival compared with AFP- median survival of 10 1/2 months. There were four CRs with one being 3 years and 6 months. The longest PR was 5 years and 8 months. These studies have demonstrated the toxicity and therapeutic activity of 131I antiferritin and the emerging role of radiolabelled antibody in cancer therapy.

Duodenal diverticulum mimicking a cystic pancreatic neoplasm.

Duodenal diverticula occur very commonly, with a prevalence as high as 22%. They are most frequently located in the second or third portions of the duodenum, and by nature of their proximity to the head of the pancreas, can be mistaken for cystic pancreatic neoplasms by diagnostic imaging. Patients with presumed cystic neoplasms of the pancreas often receive pancreaticoduodenectomies, which at high volume medical centres carry mortality and morbidity rates of 2-4% and 29-44%, respectively. Although most duodenal diverticula are recognized in single or repeat CT scans by the presence of air or contrast medium within the diverticula, we present a case in which serial CTs failed to yield any clue to the diverticulum's true nature and pancreaticoduodenectomy was performed. For presumed cystic lesions adjacent to the duodenum, barium studies, endoscopy, and/or endoscopic ultrasound-guided aspiration should therefore be pursued in addition to all available CT evidence prior to surgery.

Thoracic CT scanning for mediastinal Hodgkin's disease: results and therapeutic implications.

Thoracic CT scans were performed on 42 newly diagnosed patients with Hodgkin's disease. Five of 10 patients with negative chest X ray (CXR) had abnormal thoracic CT scans. Among the remaining 32 patients with mediastinal Hodgkin's disease (MHD) on CXR, pericardial (Ep) and chest wall invasion (Ec) were the two most common sites of involvement which were detectable by CT scan alone. All 14 cases with Ep had M/T greater than or equal to 0.30 and 14 of 21 with M/T greater than or equal to 0.30 had Ep. Six cases had extensive Ec. Ep and Ec accounted for 16 of 19 of the changes in treatment portal or philosophy based on CT scan findings. Because of the high risk of cardiac or pulmonary radiation toxicity in Ep or Ec, radiation treatment alone may be inadequate. Treatment of mediastinal Hodgkin's disease is reviewed here. The use of CT scans for identification of Ep, Ec, and other abnormalities will allow for more precise treatment, further define the use of conventional radiotherapy, combined modality therapy or whole lung irradiation, and allow more accurate analysis of treatment results.

Multi-modality treatment of primary nonresectable intrahepatic cholangiocarcinoma with 131I anti-CEA--a Radiation Therapy Oncology Group Study.

Thirty-seven patients with primary nonresectable intrahepatic cholangiocarcinoma (57% with prior treatment and/or metastasis) were prospectively treated with external radiation, chemotherapy, and 131I labelled anti-CEA. Therapy began in all trials with whole liver irradiation (21.0 Gy, 3.0 Gy/Fx, 4 days/week, 10 MV photons) with alternate treatment day chemotherapy (Adriamycin, 15 mg + 5-FU, 500 mg). One month after external beam therapy, chemotherapy was given (Adriamycin, 15 mg + 5-FU, 500 mg) followed the next day by the first administration of 131I anti-CEA. The treatment schedule used was 20 mCi day 0; 10 mCi day 5 as an outpatient. This schedule was derived from tumor dose estimates which indicated that 20 mCi (8-10 mCi/mg IgG) was sufficient to achieve tumor saturation with a tumor effective half-life of 3 to 5 days, depending upon the species of animal from which the antibody was obtained. The median tumor dose for the 20 mCi + 10 mCi regimen was 6.2 Gy. Antibody therapy was delivered in 2-month cycles using antibody generated in different species of animals; rabbit, pig, monkey, and bovine. Toxicity was limited to hematologic toxicity and was manifested as thrombocytopenia and leukocytopenia (3.2% Grade IV for each according to RTOG toxicity criteria). Tumor remission evaluated by CT scan digitized tumor volume analysis indicated a 26.6% partial response (PR). Tumor remission by physical examination indicated a 33.3% remission rate (25.9% PR and 7.4% complete remission (CR]. The median survival for patients who responded was 15.2 months. The actuarial median survival for the entire group of patients (metastases and previous treatment) was 6.5 months. The longest partial remission is presently more than 4 years.

Flexible transbronchial needle aspiration for staging of bronchogenic carcinoma.

Flexible transbronchial needle aspiration (TBNA) provides access to mediastinal lymph nodes, but its role in staging bronchogenic carcinoma is unknown. To determine the efficacy and safety of this procedure for staging the extent of mediastinal disease, the results of TBNA performed during fiberoptic bronchoscopy in 39 patients without known extrathoracic metastases were reviewed. Flexible TBNA was found to be a safe, effective method for determining the presence or absence of mediastinal metastases from bronchogenic carcinoma. Furthermore, TBNA results compare favorably with roentgenographic staging techniques, with the added advantage of providing cytopathologic information.

The solitary pulmonary nodule. Assessment, diagnosis, and management.

We have presented a brief overview of an approach that has been very successful in our hands in the patient with an SPN. Even though the patient who has undergone a thoracotomy is full of gratitude to his physician when told that the resected lesion was benign and does not question the need for the thoracotomy, we have met equally happy and gratified patients when they were told that their lesion is benign be it after CT densitometry or needle biopsy. When properly performed, these techniques demand care and attention to detail much like the surgeon performing a delicate procedure. Without proper care, these procedures can in fact reflect negatively on the physician performing them and fall in disrepute. CT densitometry and transthoracic needle aspiration biopsy allow effective management of the patient with an SPN with prompt documentation of both malignant or benign lesions. With the proper application of these techniques, the majority of patients with benign disease will not need a thoracotomy for diagnosis with resultant benefits to the patient as well as to third-party payers.

Restoration of bronchial artery circulation after canine lung allotransplantation.

To evaluate the re-establishment of the bronchial circulation in lung transplantation, we studied 10 immunosuppressed dogs up to 14 weeks after left lung allografting. Selective in vivo bronchial arteriograms were performed repetitively via the transfemoral route. In the early postoperative period, no fillinf og vessels distal of the bronchial anastomosis could be shown. After 12 days, however, continuity of the bronchial arteries across the anastomosis was present, and dye-filled ramifications of these vessels were visualized on the secondary and tertiary bronchi. Reconstitution of the bronchial circulation was also confirmed by postmortem studies after injecting the isolated descending thorasis aorta with colored radiopaque material (microfil). The bronchial mucosa at autopsy was examined microscopically. There was no correlation between its viability and bronchial artery regeneration. Although early ischemia of the transplant bronchus may be after a factor in the bronchial complcations that follow lung transplantation, the present study indicates that this ischemia is not due to failure of bronchial artery regeneration.

Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management.

Over 80 percent of patients with invasive pulmonary aspergillosis (IPA) undergoing intensive antileukemic chemotherapy in a recent two-year period survived the pulmonary infection as a result of early diagnosis and aggressive therapy with high-dose amphotericin B and 5-fluorocytosine. CT played an important role in establishing the early diagnosis of IPA and affected management. Since our original communication describing the CT findings of IPA, we have added ten new cases, each subsequently substantiated by lung biopsy (two), autopsy (two), and/or positive cultures of sputum or extrapulmonary sites (seven). The CT halo sign, or zone of lower attenuation surrounding a pulmonary mass, was present in eight of nine patients with early CT scans obtained during bone marrow aplasia. Characteristic CT progression from multiple fluffy masses to cavitation or air crescent formation suggested IPA in five of seven patients with serial CT scans. CT directly affected patient management in seven of ten cases. Scan findings were one criterion for increasing to high-dose amphotericin B or for adding 5-fluorocytosine. CT characteristics of healing IPA lesions were similar to resolving pulmonary infarcts and were used to monitor disease activity in patients on long-term amphotericin B and prior to retreatment chemotherapy.

Alveolar lavage cytology in transplanted lungs. I. Staining methods and findings in dogs with autografts and allografts without immunosuppression.

Alveolar lavages were performed repetitively on the normal and transplanted lungs of dogs that had recieved autografts or allografts without immunosuppression. One half of the lavage returns was fixed as a cytologic smear; the other half was subjected to semi-thin section or electron microscopic examination. Of the staining methods was used, the periodic acid-Schiff (PAS) and Giemsa techniques were best for differentiating and counting cells. The Ladewig technique was best for evaluating the presence and location of fibrin. After autotransplantation, the proportion of so-called alveolar marcophages increased, reached a peak in 4 to 7 days, and then returned to normal. Phagocytized fibrin increased for the first postoperative week, but not extracellular fibrin was ever observed. After allotransplantation, a progressive decrease in the proportion, size, and vacuolization of so-called alveolar macrophages was noted along with an increase in extracellular fibrin. Intracellular fibrin could be detected only up to the third day. These findings define adequate methods for preparing and staining material obtained from diagnostic alveolar lavages, and they suggest that the procedure may serve as an index of lung allograft rejection.

Initial results from an agressive roentgenological and surgical approach to acute mesenteric ischemia.

The 70% to 80% mortality rate of patients with acute mesenteric ischemia (AMI) has remained unchanged over the past 40 years. We report here the initial results using an aggressive approach to this problem. This included the earlier and more liberal use of angiography in patients at risk and the intra-arterial infusion of papaverine for the relief of superior mesenteric artery (SMA) vasoconstriction in both nonocclusive and occlusive forms of AMI. Of the first 50 patients managed by this approach, 35 (70%) had AMI demonstrated by SMA angiography, Nineteen (54%) of these 35 patients survived, including nine of 15 patients with nonocclusive mesenteric ischemia, seven of 16 with SMA embolus, two of three patients with SMA thrombosis, and the one patient with mesenteric venous thrombosis. Seventeen of the 19 survivors lost no bowel or had excision of less than 3 feet of small intestine.

The evaluation of mesoatrial shunt patency with computed tomography.

The mesoatrial shunt is performed in patients with the Budd-Chiari syndrome when the inferior vena cava is occluded and not available for a conventional portosystemic shunt. Computed tomography (CT), with injection of contrast media, was used to evaluate mesoatrial shunt patency with five examinations in four patients. Shunt patency was demonstrated by CT and confirmed by angiography in two studies. Total shunt occlusion diagnosed by CT in two additional cases was confirmed by angiography or operation. Partial graft occlusion diagnosed by CT in a fifth study was verified by both angiography and operation. CT is recommended instead of angiography in the evaluation of mesoatrial shunts because it is less invasive, it may be performed on an outpatient basis, and it yields additional useful information related to shunt patency, such as the volume of ascites, collateral vascularity, and the size of the spleen.

Pancreatitis or duodenal perforation after peri-Vaterian therapeutic endoscopic procedures: diagnosis, differentiation, and management.

The diagnosis, differentiation, and management of severe pancreaticoduodenal complications occurring after therapeutic endoscopic sphincterotomy and related procedures on the ampulla of Vater were reviewed for 254 patients. Five patients had duodenal (peri-Vaterian) perforation and six patients had clinically significant pancreatitis. Most patients were not suspected of having a significant complication the night of the procedure despite abdominal pain. Computer tomography proved to be the most accurate test for establishing the existence of a significant complication. A periduodenal collection of fluid (abscess) without significant pancreatic enlargement was the predominant complication in patients with duodenal perforation. In patients who had pancreatitis after peri-Vaterian procedures, generalized pancreatic enlargement and peripancreatic edema were most prominent. Four of the five patients with duodenal perforation required surgical drainage; all recovered. In contrast, four of the six patients with pancreatitis had medical therapy. One patient with pancreatitis died after multiple pancreatitic debridements were done. A second patient with pancreatitis who underwent exploration eventually recovered. Pancreaticoduodenal complications after therapeutic endoscopic sphincterotomy and related procedures are difficult to diagnose early; they should be suspected early and approached aggressively to limit morbidity and death.

CT diagnosis of unsuspected von Hippel-Lindau disease.

Von Hippel-Lindau disease is a hereditary disorder with complex, multi-organ involvement including retinal, central nervous system, and abdominal manifestations. We report a case of clinically unsuspected von Hippel-Lindau disease identified during computed tomography (CT) evaluation of a renal mass. The CT demonstration of a coexisting pancreatic tumor and renal cell carcinoma suggested the correct diagnosis of von Hippel-Lindau disease, which was subsequently confirmed. This case reemphasizes the value of preoperative assessment of renal tumors by CT. The finding of coexisting renal and pancreatic tumors should stimulate the search for further evidence of von Hippel-Lindau disease.

Complications of acute diverticulitis of the colon: improved early diagnosis with computerized tomography.

We have evaluated the diagnostic role of computerized tomography in 42 patients suspected clinically of having a complication of acute diverticulitis (abscess, colovesical fistula, or both). Diverticular abscesses were confirmed at operation in 10 patients. All 10 patients were diagnosed preoperatively on computerized tomography by the triad of diverticula, a segmentally thickened colon, and extravisceral fluid collection with (6 patients) or without (4 patients) associated gas. Contrast enema study suggested the presence of a diverticular abscess in only two of eight patients studied. Colovesical fistulas were confirmed in 12 patients. Eleven of 12 were diagnosed preoperatively on computerized tomography by the triad of air in the bladder, thickened colon adjacent to an area of thickened bladder, and the presence of colonic diverticula. Contrast enema examinations demonstrated the fistula in only three of eight patients studied. The remaining 20 patients proved to have uncomplicated acute diverticulitis. Findings on computerized tomography included the presence of a segmentally thickened colon with diverticula but without the findings of an abscess or a colovesical fistula. Computerized tomography correctly visualized acute diverticular complications in 21 of 22 patients and it excluded an abscess or fistula in all 20 patients with uncomplicated acute diverticulitis who were suspected of having a diverticular complication. Computerized tomography is the most sensitive and specific test for diagnosing complications of acute diverticulitis. It should be an early consideration in patients with suspected diverticular abscesses or fistulas so that appropriate therapy is not delayed.

Computed tomography assisted volumetric analysis of primary liver tumor as a measure of response to therapy.

Serial computed tomography assisted volumetric analyses were made in 33 patients with hepatoma. Thirteen of 27 patients with tumor volumes less than 2,290 cc had a partial response to experimental therapy. However, only three of these patients also demonstrated a significant change in liver volume. Tumor volume determinations made by the method described are an accurate (+/- 10%) and reproducible way to measure response to therapy. In spite of small changes in total liver volume, there may be concomitantly substantial changes in tumor volume.

Corticosteroids in clinical and experimental lung transplantation.

Lung allograft rejection can usually be diagnosed by the appearance of infiltrates on plain chest roentgenograms when these are interpreted in the light of other clinical and bacteriologic information. Large pulsed intravenous doses of methylprednisolone were usually effective in reversing lung allograft rejection that occurred in immunosuppressed dogs. In 10 of 15 animals the presence of moderate to severe rejection and its effective reversal with treatment were documented with roentgenograms and histologic sections. This ability to reverse the manifestations of lung allograft rejection, when they occur, has helped in the management of human lung allograft recipients.

Computed tomography of the pulmonary parenchyma. Part 2: Interstitial disease.

A series of patients with documented predominantly interstitial pulmonary disease was examined by routine and high-resolution computed tomography (CT) and compared to a series of twenty-one normals. Inspiratory-expiratory lung density measurements were also obtained at predetermined levels. Several basic CT signs of interstitial disease were identified: finely irregular and thickened pleural surfaces; irregular vascular shadows; thickened and irregular bronchial walls making bronchi visible over a longer portion of their course in the lungs; reticular network of lines with three patterns easily distinguishable by the size of their reticular element; hazy patches of increased density of various sizes distinguishable from alveolar filling processes by the fact that vessels can still be visualized through them; and nodules of various sizes. Micronodules are often associated with a small or medium-size reticular network and in most cases seem to represent points of confluence rather than isolated nodules. The hematogenous origin of some nodules can be specifically suggested when feeding vessels are demonstrated on thin-section scans. Nodules associated with a large network of thickened septa are suggestive of lymphangitic carcinomatosis. Inspiratory-expiratory density gradients can be more useful in confirming the diagnosis of interstitial disease than absolute measurements.

Computed tomography of the pulmonary parenchyma. Part 1: Distal air-space disease.

Because of greatly enhanced contrast resolution and the advantages of cross-sectional visualization of lung anatomy, computed tomography (CT) has the potential to add significantly to the conceptualization of parenchymal lung disease. Although the value of CT has been well documented in the detection and characterization of lung nodules, the role of CT has been less clearly defined for other types of lung disease. This report describes the CT appearance of distal air-space disease. As demonstrated by the use of inflated and contrast-injected lungs obtained at autopsy, air-space disease is definable by the following: poorly marginated nodules ranging up to 1 cm in size; coalescence of nodules; air-bronchograms and air-alveolograms; ground-glass opacification; and distinct zonal patterns of distribution, including central and peripheral configurations. These patterns of air-space abnormalities are further refined by review of case material, including examples of air-space disease secondary to aspiration and primary intraalveolar disease, evaluated by the authors over a five-year period.