Regional Mesenteric Lymph Nodes Research Articles

Diagnostic significance of mesenteric lymph node involvement in proximal small bowel Crohn's disease.

Background:The diagnosis of proximal small bowel involvement in Crohn’s disease (CD) can be challenging at magnetic resonance enterography (MRE). The inflammatory process in CD can be associated with peri-intestinal inflammatory reactions, including the presence of inflamed mesenteric lymph nodes.Objectives:To evaluate the significance of inflamed mesenteric lymph nodes adjacent to the jejunum at MRE in CD and the association with proximal bowel disease as detected by video capsule endoscopy (VCE).Design:This retrospective study was performed in two tertiary medical centres, and included 64 patients with CD who underwent MRE as well as VCE within 1 year.Methods:Data were collected for examinations performed between August 2013 and February 2021. MRE images were independently reviewed by radiologists who were blinded to the clinical data. Association between the presence of mesenteric lymph nodes adjacent to jejunum at MRE and disease activity according to VCE Lewis scores of proximal small bowel was examined.Results:VCE detected proximal disease in 24/64 patients (37.5%). Presence of regional lymph nodes in the jejunal mesentery was significantly associated with jejunal disease as seen on VCE (p < 0.001). Of the 20 patients who had proximal mesenteric lymph nodes at MRE, 15 (75%) had jejunal disease at VCE (sensitivity, 62.5%; specificity, 87.5%; and negative and positive predictive values, 79.5 and 75%, respectively). The number of regional lymph nodes was positively correlated with jejunal disease (mean: 2.63 ± 2.90 versus 0.78 ± 2.60, p = 0.01). Other MRE features of lymph nodes were not significantly predictive of jejunal CD.Conclusion:In patients with CD, inflamed regional lymph nodes in the jejunal mesentery at MRE can be valuable to suggest proximal small bowel disease, even when bowel wall features at imaging do not suggest disease involvement.Plain language summaryThe diagnosis of proximal small bowel involvement in Crohn’s disease (CD) can be challenging at magnetic resonance enterography (MRE). We analysed MRE examinations in patients with CD for the presence of lymph nodes adjacent to the proximal small bowel. We included 64 patients with CD who had MRE examinations and video capsule endoscopy (VCE) examinations within 1 year. Of 64 patients, 24 had proximal small bowel disease according to VCE. We found that of 20 patients who had regional mesenteric lymph nodes in the jejunal mesentery at MRE, 15 had proximal bowel disease involvement. We also found that patients with jejunal disease had a larger number of regional lymph nodes compared to patients without jejunal disease. All but one patient had normal appearing bowel at MRE. But, using regional mesenteric lymphadenopathy at MRE as an indicator for disease, 15/24 (62.5%) patients with proximal small bowel disease were detected. We therefore conclude that regional mesenteric lymph nodes assessment at MRE can aid diagnose proximal bowel disease, even when the proximal bowel looks normal at imaging. Presence of proximal mesenteric lymph nodes at MRE in patients with CD possibly warrant further investigation of the proximal small bowel by endoscopic measures.

Castleman lymphadenopathy: case review

Background. While examining regional lymph nodes removed with the tumor, the pathomorphologist is often limited to the exclusion of metastases, omitting changes in lymphoid tissue. The aim of the work is to describe a rare variant of Castleman-like lymphadenopathy in the surgical material obtained during the removal of colon cancer with regional lymph nodes. Methods. Pathomorphological examination of removed lymph nodes using histological and immunohistochemical methods (CD23). Results. A 73-year-old patient underwent surgery for rectal cancer. Pathomorphological analysis diagnosed adenocarcinoma of high degree of differentiation (G1) and revealed Castleman-like changes in some of the enlarged regional mesenteric lymph nodes: signs of different stages of development of lymphoid follicles, including their hyperplasia, atresia and fragmentation with preservation of activated CD23+ follicular dendritic cells and reaction of microvasculature, including vascular proliferation in the interfollicular areas with uneven narrowing of the sinuses. The discussion analyzes the probable genesis of changes in lymphoid tissue, which may be a reflection of the early stage of Castleman's disease, complication of radiation therapy performed in the preoperative stage, or a consequence of impaired immune status due to tumor growth, in particular with antigenic overloading of draining lymphoid tissue, effects of cytokines produced by inflammatory infiltrate cells that accumulate directly near the tumor, and the formation of a state of genetic instability, which progresses under the influence of radiation. Conclusion. Despite the rarity of Castleman-like lymphadenopathy, in each case of examination of lymph nodes in the surgical material it is necessary to conduct a thorough analysis of lymphoid tissue, as this may be important both to assess the prognosis and to select adequate therapy.

A Case of Collision Tumor of MALT Lymphoma and Poorly Differentiated Adenocarcinoma Diagnosed Incidentally After Appendectomy for a Clinical Presentation of Acute Appendicitis.

This report presents a case of collision tumors of low-grade B-cell lymphoma and poorly differentiated adenocarcinoma in the caceum of a 63-year-old woman. Lymphoma was diagnosed incidentally after appendectomy for a clinical presentation of acute appendicitis. Imaging follow-up demonstrated mesenteric lymphadenopathy and liver lesions, and all surgically resected regional mesenteric lymph nodes and liver biopsy were found to be infiltrated by both mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Systemic chemotherapy was administered for advanced colonic adenocarcinoma with liver metastases. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectal region is rare, and this is a previously unreported case of a patient that was diagnosed during management of acute appendicitis.

Collision tumor of low-grade B-cell lymphoma and adenocarcinoma with tuberculosis in the colon: a case report and literature review

This report presents a case of collision tumors of low-grade B-cell lymphoma and adenocarcinoma in the sigmoid colon of an 81-year-old man. All surgically resected regional mesenteric lymph nodes were found to be occupied by low-grade B-cell lymphoma, and one lymph node showed the presence of adenocarcinoma. Low-grade B-cell lymphoma was also observed in the resected spleen. Moreover, concurrent tuberculosis infection in the resected colon was proven by the presence of positive results obtained with polymerase chain reaction analysis of the mycobacterial DNA. Systemic chemotherapy was administered for advanced colon cancer with lung metastasis, and anti-tuberculosis treatment was also prescribed. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectal region is rare. Furthermore, collisions of these different entities are also extremely unusual. The accurate clinical determination of the dominant tumor and a timely follow-up are required for the proper treatment of these cases.

Extrapulmonary Small Cell Carcinoma of the Transverse Colon

Purpose: Small cell carcinoma is most commonly associated with pathologic disease, affecting the pulmonary system; however, extrapulmonary disease, although a rare entity, does occur. Areas of reported primary manifestation outside the lungs include the urinary bladder, prostate, esophagus, stomach, colon, rectum, gallbladder, cervix, kidneys, salivary glands, thymus, ovaries, and skin, amongst others. Our patient was a 75-year-old man with a past medical history significant for hypertension, who presented for a chief complaint of night sweats and constipation. His symptoms had been present for two months. There was no associated weight loss, dysphagia, odynophagia, nausea, emesis, melena, hematochezia, cough, hemoptysis, hematemesis, shortness of breath, or chest pain. The patient had no history of smoking, drug, or alcohol use. Complete blood count showed normochromic, normocytic anemia. Liver function, kidney function, electrolytes, iron studies, CXR, and quantiferon gold were all normal. A colonoscopy with biopsies revealed a tubulovillous adenoma in the transverse ascending colon and hepatic flexure with features consistent with small cell carcinoma. The patient underwent a hemicolectomy. Final pathology returned as poorly differentiated high-grade invasive neuroendocrine carcinoma without extension into or through the muscularis propria, and with clear margins of resection. Staining showed weak positivity for synaptophysin, and negative for chromogranin. Fifteen regional mesenteric lymph nodes showed no evidence of metastasis. His tumor was classified at T1N0MO, and he was started on four cycles of treatment with carboplatin and etoposide every 21 days. Colorectal small cell carcinoma is a rare entity, comprising only about 1.5% of all colorectal tumors. Of these, only 12% arise in the transverse colon. The more common sites include the rectum, cecum, and ascending colon. Available data exists in the form of either retrospective studies or case reports, so much remains to be discovered regarding the pathophysiology of disease and recommended treatment options. Currently, there are no identifiable risk factors. At the time of diagnosis, most cases have either large primary tumors with lymph node involvement or distant metastasis, liver being the most common site. There are no recommended treatment guidelines, but most cases report surgical resection combined with chemotherapy and radiation. Selection of chemotherapy as either adjuvant therapy or for metastatic disease is on a case-by-case basis.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon: Report of a case

This report presents the case of a 62-year-old man with a collision tumor of primary malignant lymphoma and adenocarcinoma in the cecum. All regional mesenteric lymph nodes that were removed surgically were found to be occupied by lymphoma cells and no lymph nodes contained any cancer cells, although the primary carcinomas did exhibit lymphatic invasion. Malignant lymphoma was also seen in the duodenum. Systemic chemotherapy was administered for the malignant lymphoma, and a complete response was thus obtained. However, just after chemotherapy multiple liver metastases of adenocarcinoma emerged, and chemotherapy against adenocarcinoma was therefore continued. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectum is rare. Furthermore, collisions of these different entities are also extremely unusual; so far only five such case reports have been published. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.

Histiocytic sarcoma in the small intestine: A case report with flow cytometry study and review of the literature

We describe a case of true histiocytic sarcoma (HS) with features of HS in clinical manifestation, histological presentation, and immunohistochemical panels. The flow cytometry studies were used for the diagnosis. The tumor presents in the small intestine with involvement of regional mesenteric lymph nodes of a 68-year-old female. Histological examination reveals that tumor cells are large and pleomorphic. They have vesicular chromatin and abundant eosinophilic cytoplasm. Immunohistochemical studies show the tumor cells to be positive for CD45 (LCA), CD45RO, CD4, CD68, and lysozyme; and negative for all other T-, B-, macrophage, follicular dendritic- and hematopoietic-cell markers. Proliferation rate is 5% by MIB stain. Flow cytometry studies reveal large atypical cells positive for CD4, CD14, and CD45. There are 29 cases of HS reported in the literature since 2001. All of these cases are summarized. The diagnostic methods and the possible prognostic factors are discussed. We believe that the correct diagnosis of HS is important for clinical treatment and prognostic prediction, although it is very rare.

Polypoid gastrointestinal stromal tumor of small bowel metastasizing to mesenteric lymph nodes: A case report

Gastrointestinal stromal tumor (GIST) is the commonest gastrointestinal mesenchymal tumor, which rarely metastasizes to lymph nodes. Therefore, unlike cases of adenocarcinoma, lymphadenectomy is seldom warranted. We describe an unusual case of a polypoid GIST of the small bowel which metastasized to the regional mesenteric lymph nodes at the time of primary surgery. The patient was a 79-year-old female who presented with partial bowel obstruction and anemia. The presented case has three unusual features, as the tumor was grossly pedunculated, microscopically pleomorphic, and featured mesenteric lymph node metastasis at the time of diagnosis.

Cytokine Expression in Paraffin Wax-embedded Tissues from Conventional Calves

The cross-reactivity of antibodies against human tumour necrosis factor (TNF)alpha, interleukin (IL)-1alpha, IL-1beta and porcine IL-6, and the distribution of immunolabelled cells were evaluated on paraffin wax-embedded tissues from five healthy calves. The tissues were fixed in 10% buffered formalin or Bouin's solution and processed for structural studies and immunohistochemical studies by the avidin-biotin-peroxidase technique. Bouin's solution proved to be the more suitable fixative and Tween 20 the most effective antigen unmasking technique for increasing detectable antigenicity. Constitutive expression of TNFalpha, IL-1alpha, IL-1beta and IL-6 by different cell populations, mainly macrophage-like cells, was detected. Lymphoid organs displayed a higher presence of immunolabelled cells than did lung, liver or kidney. TNFalpha and IL-1alpha appeared as the predominant cytokines, especially in the gut-associated lymphoid tissue of the ileum and in the regional mesenteric lymph nodes. The results will facilitate investigation of the role of these cytokine-producing cells in inflammatory disease processes in calves.

Injection of colorectal cancer cells in mesenteric and antimesenteric sides of the colon results in different patterns of metastatic diffusion: An experimental study in rats

BackgroundThis experimental study was designed to investigate the differences in pattern of local growth and diffusion of colorectal cancer cells injected into either mesenteric (M) or antimesenteric (AM) sides of the colon.MethodsA total of 1 × 106 colonic adenocarcinoma cells (line DHD/K12-TRb) were injected into the cecal wall of BDIX syngeneic male rats at an M or AM site of the colon. At six weeks after injection, all animals were sacrificed and the presence or absence of tumor in the cecum as well as regional metastasis and peritoneal carcinomatosis were determined.ResultsSix weeks after injection, macroscopic tumor growth was observed in 27/37 (72%) animals in group M and 21/32 (65%) in group AM (P = 0.98). In group AM, diffuse peritoneal carcinomatosis was present in 19/21 rats (90.4%) versus 3/27 rats (11%) in group M; this difference was statistically significant (P = 0.025). Regional mesenteric lymph nodes were the only location in which tumor was detected in 23/27 rats (85%) in group M versus 2/21 (9.5%) in group AM; this difference too was statistically significant (P = 0.031)ConclusionThe patterns of diffusion of tumors implanted in mesenteric and antimesenteric sites of the colon appear to be different, although the reason for this is not clear.

This month in Gastroenterology

This month in Gastroenterology

Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer

Enhanced motility of cancer cells by remodeling of the actin cytoskeleton seems crucial in the process of cancer invasion and metastasis. We previously identified an actin-binding protein, actinin-4, as a new biomarker of cancer invasion and an indicator of prognosis for patients with breast cancer. However, its involvement in the mechanisms of cancer invasion and metastasis remains undetermined. The current study tested the role of actinin-4 in the motility and metastatic potential of colorectal cancer cells. Quantitative immunofluorescence histochemistry showed that the expression level of the actinin-4 protein was increased in 73.1% (19/26) of the cases of colorectal cancer over the corresponding normal intestinal epithelium. The increased expression of actinin-4 was most significant in dedifferentiated cancer cells at the invasive front. A colorectal cancer cell clone capable of inducing actinin-4 using the tetracycline-regulatory system (designated DLD1 Tet-off ACTN-4) was established. Upon the induction of actinin-4, DLD1 Tet-off ACTN-4 cells spread filopodia and significantly increased their motility ( P = .00027); actinin-4 protein was concentrated at the leading edges of these actin-rich podia. When injected into the mesocecum of severe combined immunodeficient mice, DLD1 Tet-off ACTN4 cells, but not the control cells, metastasized into regional mesenteric lymph nodes, resembling the behavior of clinical cancers. The expression of actinin-4 in focally dedifferentiated cancer cells at the invasive front was significantly correlated with the frequency of lymph node metastasis of colorectal cancer ( P = .038). Actinin-4 actively increases cell motility and promotes lymph node metastasis of colorectal cancer.

Pythiosis of the digestive tract in dogs from Oklahoma.

Enteric pythiosis was diagnosed in nine dogs in Oklahoma. Eight dogs had anorexia and weight loss. Two of these dogs had diarrhea; two dogs exhibited vomiting and diarrhea; and one dog had vomiting. One dog presented with dysphagia. Seven dogs had either a palpable or radiographically visible abdominal mass. These seven dogs had localized regions of mucosal ulceration and thickened gastric or intestinal walls with some involvement of the adjacent mesentery or omentum. Two dogs had enlarged regional mesenteric lymph nodes. One dog that presented with dysphagia had an oropharyngeal mass involving the larynx and cranial esophagus. Microscopically, there was transmural chronic sclerosing and granulomatous to pyogranulomatous inflammation with arteritis. Pythium spp. were identified in all specimens by immunohistochemistry.

Metastatic model of human colon cancer constructed using orthotopic implantation in nude mice.

Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors, but these tumors rarely metastasize. This is a problem for studies into the biological behavior of metastatic subpopulations of human colorectal cancers. We have followed the evolution of the parental line and of a variant of human colon carcinoma KM12 cells, that were both tumorigenic, following implantation into the s.c. or cecal wall of nude mice. The tumors growing s.c. did not produce visceral metastases, whereas the cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. However, the incidence of liver metastases was different between the parental cell line KM12C cells and the in vivo selected cell line KM12SM cells after orthotopic inoculation. The morphological findings of KM12 cells proliferating in a monolayered sheet revealed that these two cell lines consisted of various cell populations. These results suggest that in the orthotopic colon cancer models, liver metastasis is defined by difference in subpopulations of metastatic phenotypes to the liver with early dominance of its growth in the implanted organ. As a result, our new model using orthotopic implantation of KM12SM cells, which produce a 50% incidence of liver metastasis, can help to provide a technique to study the biological behavior of metastatic subpopulations of human colon cancers.

Total Mesorectal Excision – The New Golden Standard of Surgery for Rectal Cancer

Rectal cancer persists as a significant worldwide problem. Currently, surgery is associated with a poor prognosis, a high likelihood of permanent colostomy and a high rate of local recurrence in patients with regional disease (transmural penetration or involvement of regional mesenteric lymph nodes). Functional changes such as impotence and bladder dysfunction remain distressingly common consequences of conventional surgery. Over the past two decades, a fundamental change in operative technique has taken place. Conventional surgery (which is performed using blunt technique along undefinable tissue planes) has given way to sharp dissection along definable planes. The technique known as total mesorectal excision (TME) or complete circumferential mesorectal excision (CCME) produces the complete resection of an intact package of the rectum and its surrounding mesorectum, enveloped within the visceral pelvic fasia with uninvolved circumferential margins. As a result of TME, 5-year survival figures have risen from 45–50% to 75%, local recurrence rates have declined from 30% to 5–8%, sphincter preservation has risen by at least 20% for mid- and lower rectal cancers, and the rates of impotence and bladder dysfunction have declined from 50–85% to 15% or less. Patients with rectal cancer can now have a good prognosis, and intact image and high quality of life. The integration of multidisciplinary radiation therapy and chemotherapy into the care of patients undergoing TME or CCME for rectal cancer is presently under clinical trial.

Influence of Organ Environment on Extracellular Matrix Degradative Activity and Metastasis of Human Colon Carcinoma Cells

Orthotopic implantation of human colon carcinoma cells is useful for studying the behavior of metastatic subpopulations. We observed that the parental line and variants of human colon carcinoma KM12 cells were all tumorigenic following implantation into the subcutis or cecal wall of BALB/c nude mice. Their ability to metastasize to distant organ sites varied, however, with the site of growth. Subcutaneous (SC) tumors did not produce visceral metastases, whereas cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. To examine the influence of organ environment on the extracellular matrix-degrading activity of the tumors, we inoculated human colon carcinoma cells into the subcutis or cecal wall and after 7 weeks isolated and cultured the tumors in serum-free medium. The conditioned media of SC tumors contained very low levels of type IV collagenase (gelatinase) and heparanase (heparan sulfate-specific endo-beta-D-glucuronidase), whereas the media of the cecal wall tumors contained high levels of both. Zymograms of the media revealed that the intracecal human colon carcinomas secreted more than three times the amount of latent and active forms of 92-kd type IV collagenase than did the SC tumors. Moreover, only the conditioned media of intracecal tumors contained latent and active forms of 64-kd type IV collagenase. Histochemical analysis using rabbit antiserum raised against the synthetic peptides of 72-kd procollagenase type IV showed type IV collagenase in the intracecal tumors; human colon carcinoma growing SC, however, were not stained significantly. These results suggest that factors in the organ environment may affect production and secretion of tumor extracellular matrix-degrading enzymes, and these factors may modify the metastatic behavior of human colon carcinoma cells in nude mice.

Terminally Differentiated Human Intestinal B Cells

The relative distribution of IgA and IgG subclass-producing immunocytes was examined by two-colour immunohistochemistry in normal human distal ileum including Peyer's patches (PP), regional mesenteric lymph nodes (MLN), and peripheral lymph nodes. IgA2 cells predominated slightly over IgA1 cells in the PP dome area. There was a decreasing median proportion of IgA2 cells in the order of PP (52%), distant ileal lamina propria (40%), MLN (32%), and peripheral lymph nodes (11%). The reverse was true for IgA1 cells in independent enumerations. These results support the notion that PP-derived B cells after stimulation are seeded mainly to the lamina propria of the distal gut, but that there is a substantial retention and terminal differentiation of this migrating population in regional MLN. The median subclass proportions of IgG-producing cells in the PP dome area were in independent determinations 68% IgG1, 23% IgG2, 8% IgG3, and 9% IgG4. This distribution was fairly similar to that seen in other tissue categories, except for a trend towards increased IgG1 and reduced IgG2 proportions in peripheral lymph nodes and reduced IgG1 along with increased IgG3 in normal palatine tonsils. The data suggested an association between the expression of IgG2 (and possibly IgG4) and IgA2 in intestinal mucosal immune responses.

Development of an animal model to study the biology of recurrent colorectal cancer originating from mesenteric lymph system metastases.

We developed an animal model to study the biology and therapy of local-regional recurrent colorectal cancer. Syngeneic tumor cells or human colon carcinoma cells, respectively, were injected into the lymphoid follicle of the cecum of conventional mice or athymic nude mice. The cecum was resected (at a distant site) at various time points after the injection. Recurrent disease at the site of resection and in regional mesenteric lymph nodes was found in most of the injected mice, even in those whose cecum was resected 10 min after injection. The injection of tumor cells into the lymphoid follicle of the cecum introduces tumor cells into the lymph system of the cecum and the draining mesenteric lymph nodes, and these few cells, which cannot be detected at the time of operation, are the source of recurrent disease. This new animal model should allow us to study the biology and therapy of local and regional colorectal cancer.

The effect of antigen on the development of Peyer's patches in sheep.

The proposition that the development of Peyer's patches (PP) is influenced by antigenic stimulation has been examined in sheep. Terminal lengths of ileum containing about half of the ileocecal PP were isolated from the intestinal tracts of fetal lambs during the last month before birth. Antigen was injected into some of these segments and the subsequent development of the PP studied before and after birth. The injection of either killed B. abortus, ferritin or maternal colostrum into the lumens of the isolated ileal segments did not cause premature growth of the PP follicles, nor did it effect the content of lymphoblasts in them. In contrast, the injection of these antigens into the isolated segments caused the development of germinal centers and plasma cells in the regional mesenteric lymph nodes. Plasma cells also appeared in the lamina propria along the intestinal tract in response to these antigens. These results provided experimental evidence that lymphopoiesis in the follicles of the PP of fetal lambs is not dependent on antigen. The PP in ileal segments that were not injected with antigen and had no contact with antigen subsequently grew at the normal rate before and for the first 2 weeks after birth; after this the growth of the follicles became significantly slower than normal. The follicles in these isolated ileal segments had almost completely disappeared by 3-4 months of age, whereas the follicles in the normal functional ileum did not undergo involution until around 15 months of age. The premature involution in the PP in the isolated segments was prevented by reconnecting the segment to the functional intestinal tract before 3 months of age.