Lymphogenous Spread Research Articles

Evaluation of 266 cases of hepatobiliary-pancreatic carcinoids

A review was undertaken to clarify the characteristics of carcinoids of the hepatobiliary-pancreatic (HBP) system (in the gallbladder, liver, choledochus, and pancreas) in terms of clinicopathological features, based on information obtained from a statistically reliable number of cases that to date had been unavailable. The material reviewed included 266 cases of HBP carcinoids (239 ordinary and 27 atypical varieties) cited in 338 international articles published in approximately 30 countries since 1920. The details of each case were carefully read and then computerized and analyzed in the analyzing system for gut-pancreatic endocrinoma (Niigata Registry). To avoid duplication, cases without individual identification (such as the age and sex of patients, and the institution providing the mateiials) were excluded. Where thought to be relevant for comparison, cases from the overall gastrointestinal series, consisting of 4789 cases (4606 excluding atypical varieties) similarly input into the same Registry, were referred to for comparative purposes. We found that the characteristics of HBP carcinoids were: female preponderance, except in the choledochus, small lesions (20 mm or less) in the gallbladder and choledochus, and large tumors (exceeding 50mm) in the liver at detection, a higher incidence of hematogenous compared to lymphogenous spread overall, a high incidence of carcinoid syndrome in the pancreas, compared to the other sites, and a relatively unfavorable postoperative prognosis overall.

The value of parasternal mediastinoscopy in staging bronchial carcinoma.

Computed tomography (CT) is the non-invasive staging procedure of choice for assessment of metastasis to mediastinal lymph nodes in patients with bronchial carcinoma. Cervical mediastinoscopy can provide histologic evidence of mediastinal spread to the peritracheal, tracheobronchial and subcarinal lymph nodes. Sub-aortic and para-aortic nodes cannot be sampled via this route. The present study was performed to assess the staging value of the parasternal mediastinoscopy as a separate entity. Cervical and parasternal mediastinoscopy was performed in 37 patients with a proven diagnosis of non-small cell carcinoma of the left upper lobe. In 16 patients lymph node or tumor tissue could be biopsied via the parasternal route, in 21 patients no parasternal biopsy was taken. Of the 16 cases with biopsies, only one was positive (6%). Histologic examination of lymph node biopsy tissue was false negative in one other patient (6%). Of the 21 patients without biopsies taken during parasternal mediastinoscopy, three (14%) had proven lymphogenic spread to the subaortic and para-aortic nodes, detected at thoracotomy. The parasternal procedure changed treatment in only one patient (3%). Diagnostic sensitivity was 20%. It is concluded that parasternal mediastinoscopy should not be used as a routine staging procedure in patients with left upper lobe lung cancer.

Perineural Tumor Invasion and Its Relation with the Lymphogenous Spread in Human and Experimental Carcinoma of Bile Duct. A Computer-aided 3-D Reconstruction Study.

The pathogenesis of perineural tumor invasion was studied by computer aided 3-D reconstruction of bile duct wall from two patients submitted to surgery for hepatohilar carcinoma, in order to analyze how and via what route carcinoma reaches the perineural spaces. Rabbits with VX2 carcinoma implanted in the wall of the common bile duct were also examined. It was found that carcinomas growing along the perineural spaces had abundant connections with the tumors growing outside the nerve, especially those lurking in the lymphatics. In an additional analysis on the wall tissues of bile duct from 35 patients operated for carcinoma, the degree of invasion into perineural spaces proved to correlate with that into lymphatics much higher than with venular invasion. Thus it is likely that tumors reach distant nerves mainly via lymphatics, i.e., forming satellite lymphogenous foci around nerves and then, as a second step, breaking into the perineural spaces.

Gastrointestinal Aspergillosis and Zygomycosis of Cattle

Gastrointestinal mycosis was diagnosed in 73 lesions of 32 cattle without a history of engorgement, and tissues of 29 animals were examined histopathologically. The omasum was the target organ for infection, followed by the rumen and reticulum. Acute necrohemorrhagic lesions dominated, with infiltration of neutrophils and thrombosis. The etiologic diagnosis was accomplished by indirect immunohistochemical staining of fungal elements with a panel of mono- and polyclonal antibodies raised against fungal antigens. Aspergillosis and zygomycosis were diagnosed in one or more organs of 11 (34.4%) and 20 (62.5%) cattle, respectively, and dual infections were found in three lesions of two animals. Candidosis was diagnosed in only one case. Hematogenous spread of fungi predominantly to the liver was seen in nine animals. Lymphogenic spread of aspergilli to mesenteric and omasal lymph nodes occurred in one and two animals, respectively. Factors that seemed to predispose to mycotic infection included presence of other diseases and intense antimicrobial therapy. These factors and post-partum status, which included 23 of 29 (79.3%) cows, predisposed to mycosis in several ways, e.g., reflux of acidic abomasal contents into the forestomachs, stasis of proventricular content, metabolic dysfunctions, and stress.

Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern.

Three hundred and twenty autopsy cases of sarcoidosis in Japan were analyzed to determine the pathological changes in the early stage, the mode of progression in each organ and the changes in the final stage of the disease. The lung and the mediastinal lymph nodes were affected in most of the cases, while the lesions were limited to the lung and intrathoracic nodes in some of the cases. It was suspected that early changes developed in the lung and in the hilar, and then in the mediastinal lymph nodes. The progression of sarcoid granulomas in the lung was classified into three patterns: (i) probably of a disseminated hematogenous nature; (ii) of an interstitial lymphogenous nature; and (iii) of a local expansive nature. These three patterns were observed also in the heart. In the brain, perivascular granuloma formation was a prominent feature. In the other organs in which sarcoid lesions were not malignant nor disseminated and conglomerated, no interstitial patterns were observed. In chronic cases, repeated dissemination and particularly the interstitial spread of granulomatous changes led to a prominent interstitial fibrosis and dysfunction of the organs, finally resulting in death of the individual. In such long-standing cases, the mediastinal nodes deteriorated by hyalinous degeneration of the granulomas, and many active granulomas were formed in the intra-abdominal or body surface lymph nodes. These lymph nodes were likely to continue supplying sensitized lymphocytes to the whole body. A persistence of active change in the lymph nodes and the lymphogenous spread of granulomas in organs would appear to be key factors in the prognosis of sarcoidosis.

Possible metastatic routes via portacavalshunts in renal adenocarcinoma with liver metastasis

Renal adenocarcinoma findings from autopsies on patients with and without liver metastasis (635 and 936 patients, respectively) were investigated concerning the mode of metastasis. The patients with liver metastasis showed a significantly higher frequency of metastases to the lungs, lymph nodes, contralateral kidney, adrenals, pancreas, spleen, peritoneum, and intestines; in the female patients, those with liver metastasis had a higher frequency of metastasis to the ovary and uterus than patients without liver metastasis. Some of the metastases to those organs are explainable by venous spread via portacaval shunts as well as ordinary hematogenous or lymphogenous spread, especially, those to the contralateral kidney, adrenals, spleen, intestines, or ovary.

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Pathways and Dynamics in Metastatic Spread of Lung Cancer

Changing metastatic patterns of a transplantable rat osteosarcoma.

Metastatic behavior patterns in 303 untreated Sprague-Dawley rats bearing a transplantable cerium-144-induced osteosarcoma is described. The influence of survival time, sex, age of donor and recipient animals at time of transplantation, on the development of metastasis in lungs, kidneys, lymph nodes and liver was investigated. Nearly all (98.7 per cent) rats bearing osteosarcomas in the knee region developed primary hematogeneous lung metastases and 10.6 per cent of these developed secondary metastasis in the kidneys. A further primary, lymphogenous metastatic spread occurred in 15.5 per cent of the animals. Ninety-two per cent of the rats died because of lung metastases, but animals with long survival times developed significantly more extrapulmonary metastases than animals with a shorter survival time. This is an agreement with the observed change in metastatic patterns in osteosarcoma patients with prolonged survival after adjuvant chemotherapy. Moreover, the age of the donor-tumors and the recipient animals influenced survival time and consequently metastatic patterns. It was therefore possible to keep available several groups of osteosarcoma-bearing animals with different expectations of survival time. The results of transplantation of the same tumor by the intraperitoneal and the intravenous route are also presented.

Metastatic basal cell carcinoma: Report of five cases and review of 170 cases in the literature

We report five cases of metastasizing basal cell carcinoma. The incidence of metastases in all patients with basal cell carcinomas who had surgery in the same period was 0.1%. There was no squamous differentiation in the histology of any of the primary lesions, but we found some squamous differentiation in a late recurrence in one patient and in the metastases in two patients. All other histologic features were identical in both the primary tumor and in the metastases. Perineural spread and blood vessel invasion were evident in the primary tumor and/or recurrence of three of the five patients and may be important pointers to possible recurrence and metastasis. Of 205 cases of metastasizing basal cell carcinomas mentioned in the literature, we accepted and evaluated 170 cases of tumors of the skin with histologic proof of metastasis. The male-to-female ratio was 2:1, median age at onset of primary tumor, 45 years, median interval between onset of tumor and first sign of metastasis, 9 years, median age at first sign of metastasis, 59 years, and median survival after first sign of metastasis, only 8 months. The site of the primary tumors is similar to that in nonmetastasizing basal cell carcinoma. Metastatic spread is most often to lymph nodes, lungs, and bones with lymphogenic and hematogenic spread equally frequent. Age or sex of the patient seemed to have no influence on survival or way of metastatic spread. As metastasis of basal cell carcinoma is extremely rare (1 in 1,000 to 35,000), many authors sought or postulated histologic "degeneration" into a squamous cell carcinoma, but no such unequivocal evidence has ever been found. Areas of squamous differentiation were reported in less than 15% of both primary and metastatic lesions of metastasizing basal cell carcinoma. The mode of metastatic spread and the characteristics of the histology make it rather unlikely that metastasis of a basal cell carcinoma is due to a change toward squamous cell carcinoma.

Hodgkin's disease with predominant infradiaphragmatic involvement and massive invasion of the bone marrow. A necropsic study of nine cases.

The authors report the results obtained in the necropsic study of nine cases of the so-called acute, visceral form of Hodgkin's disease (HD). Most of the patients (six men and three women, ranging from 42 to 74 years of age) lacked peripheral lymphadenopathies and had fever, weight loss, abnormality of hepatic function, and pancytopenia. Mixed cellularity was diagnosed in two, diffuse fibrosis in four, and reticular subtype of lymphocyte depletion in three cases. Despite the predominant infradiaphragmatic involvement, supradiaphragmatic lymph nodes were involved in six and tonsils in three cases. Spleen and bone marrow were involved in eight cases and the liver was involved in seven cases. In four cases there were also lesions in other extralymphoid organs. The involvement of the bone marrow was widespread and showed concurrent myelofibrosis and/or other signs of hematopoietic disturbance. There was a close relationship between the presence of vascular invasion (seven cases) and the extent of HD spread. It is concluded that despite its peculiarity, this form of HD fits the classic model of unicentric origin, lymphogenic contiguous spread, and hematogeneous dissemination, and should not be identified with any particular histologic type of HD.

Epidemiology and Treatment of Epididymitis

Epididymitis was once a common complication of gonorrhea, occurring in 10%-30% of male patients [1]. The etiology of condition was a subject of lively debate for years. Theories included lymphogenous and hematogenous spread and direct spread through vas deferens via reverse peristalsis. Pelouze [1], in 1941, cited a number of other possible etiologic mechanism, such as the rough and unscientific use of instruments in posterior urethra, irrigations or injections forcibly given, sexual excitement and excesses, violent physical exercise, digital manipulations of prostate and seminal structures, or great increases of intra-urethral and intravesical pressures. However, Pelouze rejected all of these explanations in favor of passage of urine from a full bladder down vas deferens, although he conceded that infected urine might well be helped along by one or more of cited factors. The precise method of epididymal infection remains unknown for many cases, but incidence of gonococcal epididymitis has decreased markedly since intraurethral treatments, once commonly used, have been replaced by systemic antibiotic therapy.

Distant Metastasis of Renal Adenocarcinoma in Patients with a Tumor Thrombus in the Renal Vein and/or Vena Cava

Autopsy records of renal adenocarcinoma cases were analyzed to investigate the mode of metastatic spread in instances of a tumor thrombus in the renal vein and/or vena cava. In this series of 1,828 cases 137 (7.5 per cent) had a tumor thrombus. Analysis revealed no significant differences in the incidence of the tumor thrombus between sexes or sides of primary renal involvement, or whether nephrectomy had been performed. The cases with a tumor thrombus showed higher frequencies of metastases in the liver, hepatic hilar lymph nodes and ureter, while metastases in the bones, contralateral kidney and brain were less frequent. The results suggest that bypass routes or lymphogenous spread of the tumor might be facilitated in some cases with a tumor thrombus.

Lymphography in bone and soft tissue sarcomas. Experiences from three institutions.

The case material was collected from 3 Institutions with a total of 441 patients: 217 with primary bone tumor and 224 with soft tissue sarcomas. In the majority of patients lymphography was performed during the initial diagnostic workup. The lymphograms were interpreted as negative or positive for metastases. In bone tumors, the incidence of metastases was 21%, ranging from 28% for osteosarcoma to 18% for Ewing's sarcoma and 13% for chondrosarcoma. In tumors of the soft tissue, the frequency was somewhat higher (28%), with special regard to rhabdomyosarcoma (53%), anaplastic sarcoma (67%), neurogenic sarcoma (42%) and synovial sarcoma (35%). In the group of bone sarcomas, primary hematogenous spread was 3 times more frequent than lymphogenous spread, while in soft tissue sarcomas, with a higher incidence of lymphatic spread, this finding was inverted. In the more consistent tumor groups, the occurrence of lymphatic metastases indicated a significant worsening of the prognosis. In 96 patients, lymph node biopsies were performed and the radiologic histologic correlation gave evidence of a 97.7% overall diagnostic accuracy.

Extraperitoneal Pelvioscopy: A New Aid in Staging of Lower Urinary Tract Tumors. A Preliminary Report

A new technique to obtain biopsy specimens from the pelvic lymph nodes is presented. A mediastinoscope introduced through a small incision in the abdominal wall allows the identification of the pelvic nodes. A series of 12 patients with prostatic or bladder carcinoma is presented and the feasibility of the method is documented. There was no morbidity associated with the endoscopic node biopsy. Suggestions for modification of the instrument are made. The method is now under further scrutiny to establish its place among other available methods to study lymphogenous spread of pelvic malignancies.

Leiomyosarcomas of the small intestine

Small bowel leiomyosarcomas are uncommon but potentially curable tumors often diagnosed at an advanced stage. Twenty such lesions were studied, and 19 of these produced symptoms and signs. Clinical findings included abdominal pain in 17 (85%), rectal bleeding in 8 (40%), anemia in 7 (35%), intraperitoneal perforation in 6 (30%), and abdominal mass in 4 (20%). Various abdominal x-ray examinations revealed nonspecific abnormalities (ileus, bowel obstruction, abdominal mass) in about half the cases in which they were obtained, but in only one instance was the correct diagnosis of small bowel tumor made preoperatively. Five of 12 patients undergoing resection in hope of cure survived five years. These tumors tend to metastasize by hematogenous dissemination, peritoneal implantation, local invasion, and, uncommonly, lymphogenous spread. Wide small bowel resection with adjacent mesentery is suggested for most lesions. Five year survival following resection approximates 50% in reported series.

Herpes genitalis in guinea-pigs

The kinetics of virus replication after vaginal infection of guinea-pigs with HVH 2/Angelotti were studied in relation to the appearance of local and general symptoms. Most virus was isolated from the genital tract 24-48 hours post infection. Virus was first isolated from the spinal cord 48-72 hours post infection. Penetration into the brain only occurred occasionally, and later. Under the experimental conditions employed, no virus was found in the blood, spleen, kidneys, adrenals or inguinal lymph nodes. The local symptoms (typical genital herpes) and the general symptoms (paralysis and death) started after maximum virus replication had been reached and seemed to be a consequence of neural, rather than of haematogenic or lymphogenic spread.

Early recognition and therapy of disseminated coccidioidomycosis

Fifty cases of coccidioidomycosis were first observed shortly after the onset of the disease and followed-up for as long as three years thereafter. The clinical course in forty-two patients with primary pulmonary coccidioidomycosis was compared with that of eight patients with disseminated coccidioidomycosis. It was found that certain characteristics clearly separated the two groups. (1) Soon after the primary infection, dissemination (extrapulmonary spread) could be suspected in patients with a history of weight loss, prolonged duration of generalized symptoms and chest roentgenograms showing paratracheal adenopathy. (2) Four weeks after the initial infection a presumptive diagnosis of disseminated coccidioidomycosis could be made on the basis of persistent temperature elevations, physical evidence of extrapulmonary spread (adenopathy, skin lesions, meningeal signs) and slow clearing as seen on chest roentgenograms. (3) Skin test anergy usually appeared as serum complement fixation titers rose to a disseminated range, but lagged behind those clinical signs which indicated extrapulmonary spread. (4) Dissemination occurred within seven weeks of the primary infection in seven patients and was first recognized in week 20 in the eighth. (5) Diagnosis of disseminated disease was confirmed by isolation of C. immitis from an extrapulmonary site or maximum coccidioidal complement fixation titer of 1:32 or greater. Early ambulation and return to duty failed to have an adverse effect on forty-two patients with primary pulmonary coccidioidomycosis. An elevated erythrocyte sedimentation rate was not regarded as a contraindication to discharge. All patients healed without receiving amphotericin B therapy and evidence of dissemination was not seen in any patient for as long as fifty-two weeks. Amphotericin B was an effective agent in the therapy of disseminated coccidioidomycosis. Five patients received a total intravenous dosage of 1.15 to 6.39 gm. for five to forty-one weeks. All exhibited a fall in coccidioidal complement fixation titer and disappearance of physical and roentgenologic evidence of disease. Evidence of exacerbation was not encountered up to sixty-four weeks after infusions were stopped. Response in a patient with lymphogenous dissemination was clearly better than in an untreated control patient. Reversible renal abnormalities were the major manifestations of amphotericin B toxicity in all patients, but this did not preclude its use. It is recommended that amphotericin B therapy be started as soon as a diagnosis of extrapulmonary spread from primary pulmonary coccidioidomycosis is made. A total dosage of 1 to 2 gm. over a period of four months is usually adequate for patients treated soon after the original lymphogenous spread. Those treated later in the course of the disseminated disease require from 4 to 6 gm. for eight to twelve months after treatment is started. In all patients with disseminated disease, therapy is given in divided doses until cultures, total leukocyte count, chest roentgenogram, erythrocyte sedimentation rate, weight and temperature are normal, and the coccidioidal complement fixation titer has fallen to a low value (1:4 or below).

Enviromental versus constitutional factors in the development of tuberculosis among Negroes.

Although tuberculosis morbidity and mortality are higher among Negroes than among whites, is no unanimity of opinion as to whether this is due to environmental factors or to a constitutionally lower resistance of the Negro to this disease. Pinner and Kasper (1) found marked differences at autopsy in the response to tuberculosis of adult Negroes and whites, indicating a lower resistance in the Negro. The differences consisted of a greater frequency in the Negro of hematogenous and lymphogenous spread of the tuberculous disease, of massive caseation of lymph nodes, and of exudative lesions which do not respect normal anatomic boundaries of organs. Rich (2), also on the basis of autopsy findings, reports that there is definite clinical and anatomical evidence that the Negro very commonly reacts to the 'tubercle bacillus in a manner which is different from that characteristic of the white race. The clinical and roentgenographic studies of Israel and Payne (3) bear out the necropsy studies in that they found a group difference in the characteristics of tuberculosis among ~hites and Negroes, but they state that anatomically typical childhood-type tuberculosis is apparently rare in white adults and infrequent in adult Negroes. These reports leave little doubt that is a difference in the type of response of the two races to infection with tubercle bacilli. They do not however indicate the relative importance of thi~ differenc~ in the total picture of tuberculosis morbidity and mortality, nor do they offer an explanation for it. Pinner and Kasper recognize this in their warning that their study was based upon autopsy material only, and that conclu-