Para-aortic lymph node metastasis in carcinoma of the distal bile duct

BACKGROUND/AIMS: Lymph node dissection plays an important role in radical surgery for pancreaticoduodenal carcinomas. The aim of this study was to identify the critical areas of lymph node dissection in carcinoma of the distal bile duct. METHODOLOGY: Between January 1995 and December 1996, 20 consecutive patients with distal bile duct cancer underwent pancreaticoduodenectomy with extended lymph node dissection (including the para-aortic nodes). Histopathologic findings were examined with special reference to lymph node metastasis. RESULTS: Histological evidence of lymph node metastasis was found in 11 patients (55%). The areas with frequent metastases were the posterior pancreaticoduodenal lymph nodes (35%), and the nodes around the hepatoduodenal ligament (35%) and around the common hepatic artery (30%). Para-aortic lymph node involvement was identified in 5 patients (25%). Most of these existed in the inter-aorticocaval space. Pancreatic parenchymal invasion was present in 10 patients. Half of the patients with pancreatic invasion had para-aortic nodal involvement. Para-aortic lymph node metastasis was significantly associated with pancreatic parenchymal invasion (p<0.05). CONCLUSIONS: In carcinoma of the distal bile duct with pancreatic parenchymal invasion, extended lymph node dissection (including para-aortic nodes) should be undertaken because of the relatively high incidence of metastasis.     

An electrophysiological study of the action of crude Enhydrina schistosa venom

Complementary techniques to laparotomy are required to monitor patients with lymphomas both before and after treatment. Our preliminary experience with grey-scale ultrasonography is presented. Fifty-two patients, themajority with Hodgkin's disease or other lymphomas, were examined with ultrasound equipment which was custom built. The essential difference between grey-scale equipment and conventional machines is the ability to display the internal consistency of soft organs. Of 20 spleens examined prior to splenectomy, the ultrasonic scan was considered suggestive of involvement in seven of nine that showed histological evidence of Hodgkin's disease. Threeof 11 histologically negative spleens were considered to be positive preoperatively and two of nine read as negative on the scan contained histological disease. Fifty livers were examined with ultrasound. Of seven patients with histological involvement four were read as positive and three as negative and six of 43 patients with no macroscopic or microscopic evidence of liver infiltration were also considered to have a positive ultrasonic scan. Ultrasonic scanning has proved useful for demonstrating enlarged lymph nodes in the porta hepatis, upper para-aortic lymph nodes and bulky mesenteric nodes. On the basis of these preliminary observations the potential value and application of the technique is discussed.     

Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model

Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL-2 at 25,000-50,000 units/ day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para-aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1-1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/ day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para-aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.     

A case of advanced gastric carcinoma with disappearance of cancer cells by neoadjuvant chemotherapy

A 74-year-old man was diagnosed by preoperative X-ray and endoscopy with biopsy as having type 2 advanced gastric carcinoma (poorly differentiated adenocarcinoma) in the antrum. CT scan revealed swelling of the paraaortic lymph nodes, which was considered to be metastasis from the gastric carcinoma. As the cancer was judged to be stage IV and too advanced for a curative surgical resection, a neoadjuvant chemotherapy was initiated. One course of the regimen consisted of 10 mg of CDDP (day 1-5, drip) and 300 mg of UFT (day 1-7, oral), and the patient underwent the regimen three times in succession. After the chemotherapy, the swelling of para-aortic lymph nodes disappeared on CT scan. A distal gastrectomy with D2 lymph nodes dissection and sampling of the para-aortic lymph nodes was performed. Histopathological examination revealed that the cancer cells had completely vanished both in the primary tumor and lymph nodes. The effect of this neoadjuvant chemotherapy was judged to be Grade 3 histopathologically.     

Regional intralymphatic infusion (ILI) of irradiated tumor cells with evidence of distant effects

A case of canine lymphoma with radiographically-documented involvement of the para-aortic nodes is reported. Intralymphatic infusions (ILI) of cultured irradiated autochthonous tumor cells to remote lymph node bearing areas were associated with a dramatic initial shrinkage of the para-aortic lymphadenopathies. Three ILI timing schedules were used consecutively during a course of 10 treatments, allowing a comparison of responses in the same animal. The reported case suggests that a normal lymph node can be effectively "stimulated" by the same agent approximately every 3 weeks. A possible schedule for intralymphatic infusion is proposed for further investigation.     

Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell

A recombinant H-2Kb transgene, GK, containing the human HLA-G gene promoter is expressed throughout the trophoblast when inherited paternally. Male GK transgenic mice were mated with female T-cell receptor (TCR) transgenic mice to assess the effect of fetal H-2Kb expression on maternal H-2Kb-specific CD8+ T-cells during pregnancy. The number of maternal H-2Kb-specific CD8+ T-cells in spleen increased significantly (approximately 3-fold) 10 days post coitus when the GK transgene was inherited from the father. A smaller (approximately 2-fold) increase was observed in the spleen of pregnant females mated with C57BL/10 (H-2b) males. No increase was observed in mothers mated to syngeneic male mice. In both cases where expanded cohorts of maternal CD8+ T-cells were observed the amount of surface CD8 and to a lesser extent, TCR molecules was reduced. No change in the amount of surface CD44 or CD45RB was detected when levels were compared with naive T-cells from control virgin female mice. Expanded cohorts of CD8+ T-cells were also detected in para-aortic and inguinal lymph nodes draining the uterus but no changes were observed in mesenteric lymph nodes. This study concludes that maternal CD8+ T-cells are exposed to paternally inherited fetal MHC class I antigens during pregnancy. Moreover, the phenotype of the CD8+ T-cells in maternal spleen and lymph nodes that drain the uterus is not typical of activated, antigen-experienced T-cells suggesting that contact with fetal H-2Kb molecules induces a state of functional unresponsiveness.     

Blockage of mesenteric lymphatic flow in rats

An experimental model of blockage of the mesenteric lymphatic flow (MLF) in rats was designed, and morphologic changes of mesenteric lymphatic vessels (MLV) and lymph nodes were investigated by mesenteric lymphangiography and histopathologic examination. Body weight in rats with blockage of MLF did not increase normally. Mesenteric lymphangiography revealed dilation of the MLV, reverse flow into the peripheral MLV, and leakage of contrast medium, resulting in chylous ascites. Remarkable dilation of the lymphatic sinuses and dilated and increased rough endoplasmic reticulum in lymphocytes in the mesenteric lymph nodes due to lymph stagnation were observed by light and electron microscopic examination, respectively.     

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.     

Translocation of Escherichia coli from the gastrointestinal tract to the mesenteric lymph nodes in gnotobiotic mice receiving Escherichia coli vaccines before colonization

Germfree mice were immunized orally or intraperitoneally for 6 weeks with heat-killed vaccines of indigenous Escherichia coli or nonindigenous E. coli O 127: B8 before colonization with these strains. The mice exhibited increases in specific serum antibodies and intestinal immunoglobulin A reacting with the E coli antigens. Prior immunization did not reduce the gastrointestinal population levels of the E. coli strains attained 3 and 7 days after colonization. Neither oral nor intraperitoneal immunization with the E. coli strains before colonization decreased the incidence of bacterial translocation to the mesenteric lymph nodes or reduced the number of viable E. coli cells per mesenteric lymph node. There also was no relation in individual mice between serum antibody titers and the numbers of viable E. coli cells translocating to the mesenteric lymph nodes. Thus, prior vaccination with E. coli in this study did not decrease the incidence or reduce the numbers of viable E. coli translocating to the mesenteric lymph nodes in gnotobiotic mice monoassociated with E. coli.     

Low molecular weight silicones are widely distributed after a single subcutaneous injection in mice

To examine the distribution of low molecular weight silicones in body organs, separate groups of female CD-1 mice were injected with either breast implant distillate composed primarily of hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, and tetradecamethylcycloheptasiloxane or a polydimethylsiloxane oil containing low molecular weight linear siloxanes. Mice were injected subcutaneously in the suprascapular area and killed at different times. Levels of individual low molecular weight silicones were measured in 10 different organs (brain, heart, kidney, liver, lung, mesenteric lymph nodes, ovaries, spleen, skeletal muscle, and uterus). In mice treated with the cyclosiloxane mixture and killed at 3, 6, or 9 weeks, highest levels of cyclosiloxanes were found in the mesenteric lymph nodes, ovaries, and uterus, but all organs examined contained cyclosiloxanes. In a cohort killed at 1 year, most organs contained measurable cyclosiloxanes with highest levels in mesenteric lymph nodes, abdominal fat, and ovaries. Of the individual cyclosiloxanes measured, selective retention of decamethylcyclopentasiloxane and dodecamethylcyclohexasiloxane relative to octamethylcyclotetrasiloxane was seen in all organs at all time points studied. Organs from animals receiving the linear siloxane mixture were harvested at 9, 12, and 15 weeks. We found maximum levels in the brain, lungs, and mesenteric lymph nodes, but all other organs contained measurable levels. These data are, to the best of our knowledge, the first demonstration that after a single subcutaneous injection silicones are widely distributed throughout the body and can persist over an extended period.     

The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes

Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.     

Lymphatogenous spread of renal cell carcinoma: an autopsy study

PURPOSE: We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS: From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.     

Computed tomography, ultrasound and lymphography in the diagnosis of malignant lymphoma

Lymphographic findings were compared with the results at histopathology in 42 laparotomized patients with malignant lymphoma. Of 12 patients with lymphographically suggested lesions in normal-sized lymph nodes, only one had pathologic changes at histologic examination. Computed tomography gave a better idea of the extent of the disease than lymphography. Moreover, CT had an equal diagnostic accuracy as lymphography for demonstrating enlarged para-aortic lymph nodes. CT should therefore be able to replace lymphography in examination of malignant lymphoma. Ultrasound had the same diagnostic accuracy as CT regarding the upper and middle abdomen but not in the lower abdomen. Ultrasound is of special value in thin patients and when guided needle biopsy is required.     

Enlarged hilar and mediastinal nodes (and especially lower right hilar node enlargement) as a sign of metastasis of a renal tumour

Hilar and mediastinal node enlargement may be a manifestation of the spread of renal tumours. However, the author believes the spread to these nodes may occur either via the upper para-aortic nodes or directly by way of lymphatic vessels from the kidneys by-passing the upper abdominal nodes. It seems that in some cases the hilar node may even be acting as a regional lymph node for the kidney. Thus an enlarged hilar node and especially a lower right hilar node may be the presenting feature of a renal tumour.     

Distribution and contrast enhanced CT appearance of abdominal tuberculous lymphadenopathy

PURPOSE: To clarify the contrast enhanced CT features and anatomic distribution of the disseminated vs non-disseminated tuberculosis (TB) involving abdominal lymph nodes. MATERIALS AND METHODS: The contrast enhanced CT findings of abdominal lymphadenopathy in 25 patients, including disseminated TB associated with miliary TB of the lung (n = 5) and non-disseminated TB (n = 20), were retrospectively evaluated in a blind review to assess our criteria of morphology, density and location of the involved lymphadenopathy. RESULTS: The enhancement patterns of disseminated TB were not different from those of non-disseminated TB. Ninety-six percent of the patients had peripheral rim enhancement, and 60% showed a multilocular appearance. The enlarged lymph nodes of TB were less than 4 cm in diameter. Lymphadenopathy caused by hematogenous dissemination often accompanied splenic involvement showing multiple low-density foci in the spleen. The predominant sites of lymphadenopathy of disseminated TB were hepatoduodenal ligamentous, hepatogastric ligamentous, mesenteric, and both upper and lower portions of the retroperitoneal lymph nodes, whereas non-disseminated TB mainly involved hepatoduodenal ligamentous, hepatogastric ligamentous, mesenteric and upper retroperitoneal lymph nodes, excluding the lower retroperitoneal lymph nodes. By combining contrast enhancement patterns and the anatomic distribution of lymphadenopathy shown on the contrast enhanced CT images, reviewers made a correct diagnoses of tuberculosis in 94%, of cases, with a specificity of 95% and sensitivity of 92%. CONCLUSION: Contrast enhanced CT patterns correlate well with the pathologic features of tuberculous lymphadenopathy. A different anatomic distribution between disseminated and non-disseminated TB involving the lower retropentoneal lymph nodes was recognized in this study.     

Bone and calcium metabolism in Werner''s syndrome

Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis (PCM), was first isolated from armadillos from the Amazonian region where the mycosis is uncommon. In the present study, we report on the high incidence of PCM infection in armadillos from a hyperendemic region of the disease. Four nine-banded armadillos (Dasypus novemcinctus) were captured in the endemic area of Botucatu, Sao Paulo, Brazil, killed by manual cervical dislocation and autopsied under sterile conditions. Fragments of lung, spleen, liver, and mesenteric lymph nodes were processed for histology, cultured on Mycosel agar at 37 degrees C, and homogenized for inoculation into the testis and peritoneum of hamsters. The animals were killed from week 6 to week 20 postinoculation and fragments of liver, lung, spleen, testis, and lymph nodes were cultured on brain heart infusion agar at 37 degrees C. Paracoccidioides brasiliensis was isolated from three armadillos both by direct organ culture and from the liver, spleen, lung, and mesenteric lymph nodes of hamsters. In addition, one positive armadillo presented histologically proven PCM disease in a mesenteric lymph node. The three armadillos isolates (Pb-A1, Pb-A2, and Pb-A4) presented thermodependent dimorphism, urease activity, and casein assimilation, showed amplification of the gp43 gene, and were highly virulent in intratesticularly inoculated hamsters. The isolates expressed the gp43 glycoprotein, the immunodominant antigen of the fungus, and reacted with a pool of sera from PCM patients. Taken together, the present data confirm that armadillos are a natural reservoir of P. brasiliensis and demonstrate that the animal is a sylvan host to the fungus.     

Trypanosoma cruzi infection in mice enhances the membrane expression of low-affinity Fc receptors for IgG and the release of their soluble forms

The membrane expression of low-affinity Fc receptors for IgG (Fc gamma RII/III) on cells and the number of Fc gamma RII/III(+) cells were studied by flow cytometry, using the 2.4G2 MoAb, in mice infected by Trypanosoma cruzi. Cells from spleen, mesenteric lymph nodes and peritoneum were collected on days 10, 20, 30 and 40 post infection (p.i.). The in vivo serum level of soluble Fc gamma RII/III, as well as its in vitro release by cells from infected mice were studied. Parasitaemia and IgG1, IgG2a and IgG2b T. cruzi-specific antibody titres were also recorded. Both the expression of Fc gamma R on cell membrane and the absolute number of Fc gamma R(+) cells increased in spleen and in mesenteric lymph nodes, but not in peritoneum. The modifications in spleen occurred in the early and late parasitaemic phase of infection, i.e., before and after detection of T. cruzi-specific antibodies (from day 10 to 40 p.i.). In mesenteric lymph nodes, the variations were observed only in the early acute infection, when antibodies were not yet detectable at significant levels (on days 10 and 20 p.i.). Higher levels of soluble Fc gamma R were detected in sera and in culture supernatants of spleen and lymph node cells from day 20 to 40 p.i. These results show that T. cruzi infection in mice upregulates the expression and the release of Fc gamma RII/III, in the acute phase of infection, before as well as after the rise of antibody response.     

Pharyngitis: how can so simple a disease be so complex?

Intestinal non-Hodgkin's lymphomas are a rare complication of long-standing Crohn's disease and generally arise in sites of active inflammatory disease. To our knowledge, we report the first case of an unusual association between ileal Crohn's disease and a diffuse large B-cell non-Hodgkin's lymphoma involving an adjacent mesenteric lymph node but not the intestinal tract. A 22-year-old man was seen for intermittent abdominal pain, vomiting, and severe weight loss that were suggestive of intestinal obstruction. A segmental ileocolonic resection was performed. Gross examination revealed a terminal ileal inflammatory stenosis and enlarged mesenteric lymph nodes. Histologically, terminal ileal Crohn's disease was associated with a diffuse large cell lymphoma localized within one mesenteric lymph node without intestinal involvement. Immunophenotyping performed on deparaffinized sections demonstrated the B phenotype of this lymphoma.