Submucosal Lymphatics Research Articles

Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves

Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice. PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region. We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse. Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice. This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.

Chronic diarrhea in a toddler – A case of intestinal lymphangiectasia

Intestinal lymphangiectasia (IL), a rare form of protein losing enteropathy, is a benign condition characterized by focal or diffuse dilation of the mucosal, submucosal, and subserosal lymphatics causing loss of lymph fluid into the gastrointestinal tract, leading to edema, hypoproteinemia, lymphocytopenia, hypogammaglobulinemia, and immunological abnormalities. This is a case report of an 18-month-old male child who presented to us with complaints of diarrhea for 6 weeks associated with failure to thrive but without fever and edema which was diagnosed as IL on gastroenteroscopy and confirmed by histopathology.

Platy Talc, Asbestos, and Talc Fibers in the Female Genital Tract in Patients with Ovarian Cancer

Abstract Introduction/Objective Recent analyses on human tissue help inform the discussion regarding talc and ovarian cancer, by showing that, in some patients, considerable talc can migrate to multiple organ sites in the pelvic region from perineal application. Recently, we showed that birefringent particles were seen by polarized light microscopy and shown to be talc by scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDS) and/or Raman spectroscopy in surgically resected tissues from patients with ovarian carcinoma and perineal talc exposure. These sites included ovary, cervix, fallopian tube, uterine serosa, and regional lymph nodes. Fibrous talc, with greater carcinogenic potential as determined by the International Agency for Research on Cancer, may be observed in pelvic tissues. Besides ascension through the reproductive tract, particles and fibers may gain entry to pelvic organs by accessing small submucosal lymphatics in the lower part of the tract. Both platy and fibrous talc have an Mg-Si elemental signature, weight % Mg/Si ratio within 5% of the theoretical value of 0.649, and thus are distinguishable from other exogenous substances including the various subtypes of asbestos. Methods Tissue-based analytic methods (including in situ SEM, where a paraffin block is examined directly under variable pressure) are critical in the detection of talc and asbestos, particularly since they preserve architecture, and demonstrate talc and/or fibrous particles within their histologic environment; this may help inform exposure origin and pathophysiologic significance. Results We reviewed the analytic outcomes of our consultative experience to date. This showed that 180 of 196 patients with a history of perineal talc exposure had birefringent particles seen by light microscopy in surgically resected pelvic tissues, and 82 of 91 had talc confirmed by SEM/EDS. Carcinogenic fibers were found in 28/82 (34%) of these patients, with talc fibers only (19/82 patients, 23%), asbestos (7/82, 9%) or both (2/82, 2%) confirmed by SEM/EDS. Conclusion Our study confirms that talc and toxic fibers may be found in human pelvic tissues of talc-exposed patients. Because the SEM/EDS method samples only a small amount of tissue relative to what is in the paraffin block, the finding of exogenous particles by this method typically translates to a high overall particle burden, when scaled mathematically to bulk tissue.

Abstract No. 589 Utility of dynamic contrast magnetic resonance lymphangiography in the diagnosis and treatment of plastic bronchitis

Recently, intranodal lymphangiography (IL) and thoracic duct embolization (TDE) have been described as a treatment of plastic bronchitis. Additionally, dynamic contrast MR lymphangiography (DCMRL) has been used to detail the central lymphatic anatomy prior to TDE. The purpose of the present study is to examine the utility of preintervention DCMRL for treating patients with clinically diagnosed plastic bronchitis (PB). Review of IR QA database (Hi-IQ) was performed to identify patients referred for TDE. Between 2016-19, 46 patients (21F:25M, mean age 51 years) were referred to interventional radiology for treatment of clinically diagnosed PB. Medical records were reviewed for imaging (DCMRL and IL) findings and outcome of TDE. Of the 46 patients referred for PB, 37 underwent DCMRL prior to IL and TDE. Reasons pts did not undergo DCMRL included obesity (n = 7), pacemaker dependent (n = 1), and critically ill (n = 1). In 32/37 patients (86%), DCMRL demonstrated abnormal lymphatic perfusion of central bronchi or lungs arising from the TD indicating a lymphatic etiology of PB. In the remaining 5 subjects, lymphatic anatomy was normal. All 37 patients subsequently underwent IL and TD cannulation for TDE. IL/TDE confirmed aberrant lymphatic perfusion in 32/32 (100%) of patients with DCMRL findings diagnostic for lymphatic etiology of PB. In the 5 patients with normal DCMRL, the IL and cannulation of the TD were also normal. Lymphazurin blue was injected into the TD via a microcatheter while bronchoscopy was performed in these 5 patients, and none were found to have the dye appear in the submucosal lymphatics of the airway, further confirming abnormal pulmonary lymphatic perfusion was not present. The PPV and NPV of DCRML for lymphatic origin of PB was 100% (P <0.001). In the 32/37 patients with positive DCMRL, TDE was performed with coils and N-BCA glue. In 31/32 embolized patients, symptoms resolved completely. In one patient, symptoms resolved but recurred requiring a second TDE. DCRML has a high PPV and NPV for confirming a lymphatic etiology of PB. These findings suggest DCMRL should be performed on all patients with PB to confirm the etiology of PB prior to undergoing TDE.

Primary intestinal lymphangiectasia in a 23-month- old girl

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy which is defined as dilation of existing mucosal, submucosal, or subserosal lymphatics within the gastrointestinal tract. That causes loss of lymph fluid into the gastrointestinal tract, leading to the development of hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunologic anomalies. It is usually diagnosed in patients younger than 3 years old and is rarely first diagnosed in adulthood. Here we have a case report in a 23-month- old female presented with the complaint of peripheral edema and diarrhea. The diagnosis of PIL was made through upper gastrointestinal endoscopy and pathology histologic analysis. Patient placed on oral supplements of medium-chain triglycerides, a high protein diet, supplements of fat-soluble vitamins and responded well.

RA02.05: IS ROUTINE SUBCARINAL LYMPH NODE DISSECTION NECESSARY IN SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA?

Abstract Background Esophageal squamous cell carcinoma (ESCC) tends to metastasize in a multidirectional fashion through the extensive submucosal lymphatics, even in early stage. Subcarinal lymph nodes (LNs) is regarded as one of regional lymph node stations for esophageal cancer and suggested to be dissected by Guildlines. However, the metastatic rate of subcarinal LNs is relatively low and dissection reportedly may increase pulmonary complications. The purpose of this study was to investigate the impact of subcarinal LN dissection on short-term and long-term outcomes in patients with superficial ESCC and aimed at illustrating the value of subcarinal LN dissection in superficial ESCC. Methods From January 2010 to December 2015, 490 patients with pT1 ESCC were enrolled in the study. Patients in subcarinal dissection (Group 1) or non-dissection group (Group 2) were matched randomly in a 2:1 ratio, eventually, 255 patients were selected for further statistical analysis. Results The metastasis rate of subcarinal LNs in superficial ESCC was 1.24% and significantly lower than perigastric, paraesophageal or bilateral recurrent laryngeal nerves station (7.14–9.96%). Compared with Group 1, Group 2 had shorter operation time (193 ± 35 vs. 204 ± 39, P = 0.016), less blood loss (157 ± 48 vs. 178 ± 29, P = 0.011), less harvested LNs (20.7 ± 8.8 vs. 24.5 ± 9.5, P = 0.002) as well as lower incidence of pulmonary complications (9.4 vs. 20%, P = 0.032). At a median follow-up of 46 months, the recurrent rates in two groups were similar (16.5 vs. 15.3%, P = 0.809). The 3-year overall survival(OS) rate of Group 1 and 2 was 89.7% and 90.4%, correspondingly, the 3-year disease-free survival (DFS) was 83.5% and 88.5%, respectively. Survival analysis revealed no OS (P = 0.992) and DFS (P = 0.665) reductions in Group 2. Subgroup analyses stratified by pT and pN status also confirmed no significant differences in OS and DFS. In univariate and multivariate analyses, subcarinal LN dissection was not a predictive factor of prognosis in superficial ESCC. Conclusion The present study was the first available analysis investigating values of subcarinal LN dissection in superficial ESCC. Our results showed subcarinal LN dissection did not contribute to improved survival, whereas may increase the risk of postoperative pulmonary complications in superficial ESCC. Therefore, subcarinal LN dissection could be omitted for patients with superficial ESCC. Disclosure All authors have declared no conflicts of interest.

Pattern of lymph node metastases of squamous cell esophageal cancer based on the anatomical lymphatic drainage system: efficacy of lymph node dissection according to tumor location.

Knowing the anatomical lymphatic drainage of the esophagus is crucial to understanding the dissemination pattern of esophageal tumor. During the embryonal growth, the middle and lower part of the esophagus stretches as the lymphatic networks develop in the submucosal layer. The abundant submucosal lymphatics drain in a longitudinal fashion directly to their proximal and distal ends. The lymphatic route from the proximal esophagus through recurrent nerve nodes to supraclavicular nodes are a component of the mesentery of the proximal esophagus. The lower esophagus mostly drains its lymph into paracardial nodes related to celiac nodes through the mesentery of the distal esophagus. Lymphatic routes to mid and lower paraesophageal nodes usually originate from the intermuscular area of the muscularis propria. The lymphatic communication between the submucosa and intermuscular area is limited. The anatomical concept was confirmed clinically by a large series of single institution and the nationwide registry in Japan. The clinical data for the incidence of involved nodes verified the anatomical observations that long longitudinal extension of lymphatic drainage in the submucosa connected to the upper mediastinum lymphatics and paracardial lymphatics. The extent of dissection should be not tailored according to the anatomical distance from the tumor but according to the incidences of metastasis of each area, those were differed by tumor location. The areas for node dissection should be modified according to the tumor location. Although in patients with tumor limited to within the submucosal layer, even with tumors located in the mid- and lower esophagus, lymphatic metastasis was frequent in the upper mediastinum and perigastric area via the abundant submucosal lymphatics in a longitudinal fashion. When tumor invades or penetrates the muscle layer, the incidence of paraesophageal lymph node metastasis in the middle and lower mediastinum increases.

Inguinal mass: An unusual presentation of gastroesophageal junction adenocarcinoma

Gastroesophageal junction (GEJ) tumors are inherently aggressive owing to their location near vital structures and early lymphatic spread. The usual symptoms at presentation are dysphagia, regurgitation, and weight loss. Lymphatic involvement is seen early due to abundant submucosal lymphatics and is an important prognostic marker. Nodal involvement is frequently seen in the mediastinum and abdomen as these are the loco-regional nodal basins. Nodal spread beyond these basins is infrequent. We report a case of GEJ adenocarcinoma with inguinal mass secondary to inguinal nodal metastasis as a presenting symptom.

An unusual presentation of colonic metastasis of adenocarcinoma of the lung

Abstract A 49-year-old male presented with difficult, painful defecation. Colonoscopy revealed a circumferential mass of the descending colon. A biopsy showed submucosal lymphatics engorged with tumor cells. Immunoperoxidase stains suggested that the tumor probably represented a metastasis from the lung. Computed tomography of the chest showed a right lung mass. The patient died four weeks after initial diagnosis. The primary tumor was an adenocarcinoma of the lung which had metastasized to the colon. This is unusual compared to the more-common metastatic squamous cell carcinoma. This case demonstrates the importance of recognizing the presence of metastasis in a colonic lesion, establishing its histologic type and identifying the site of the primary tumor using immunohistochemistry.

Phenotypic characterization of cells participating in transport of prion protein aggregates across the intestinal mucosa of sheep

The oral route is considered to be the main entry site of several transmissible spongiform encephalopathies or prion diseases of animals and man. Following natural and experimental oral exposure to scrapie, sheep first accumulate disease associated prion protein (PrPd) in Peyer’s patch (PP) lymphoid follicles. In this study, recombinant ovine prion protein (rPrP) was inoculated into gut loops of young lambs and the transportation across the intestinal wall studied. In particular, the immunohistochemical phenotypes of cells bearing the inoculated prion protein were investigated. The rPrP was shown to be transported across the villi of the gut, into the lacteals and submucosal lymphatics, mimicking the transport route of PrPd from scrapie brain inoculum observed in a previous intestinal loop experiment. The cells bearing the inoculated rPrP were mainly mononuclear cells, and multicolor immunofluorescence procedures were used to show that the rPrP bearing cells were professional antigen presenting cells expressing Major histocompatibility complex II (MHCII). In addition, the rPrP bearing cells labeled with CD205, CD11b and the macrophage marker CD68, and not with the dendritic cell markers CD11c and CD209. Others have reported that cells expressing CD205 and CD11b in the absence of CD11c have been shown to induce T cell tolerance or regulatory T cells. Based on this association, it was speculated that the rPrP and by extension PrPd and scrapie infective material may exploit the physiological process of macromolecular uptake across the gut, and that this route of entry may have implications for immune surveillance.

Exosome-producing follicle associated epithelium is not involved in uptake of PrPd from the gut of sheep (Ovis aries): an ultrastructural study.

In natural or experimental oral scrapie infection of sheep, disease associated prion protein (PrPd) often first accumulates in Peyer's patch (PP) follicles. The route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. In a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated PrPd was detected by light microscopy shortly (15 minutes to 3.5 hours) after inoculation in the villous lacteals and sub-mucosal lymphatics. No PrPd was located within the follicle-associated epithelium (FAE), sub-FAE domes or the PP follicles. To evaluate this gut loop model and the transportation routes in more detail, we used electron microscopy (EM) to study intestinal tissues exposed to scrapie or control homogenates for 15 minutes to 10 days. In addition, immuno-EM was used to investigate whether exosomes produced in the FAE may possess small amounts of PrPd that were not detectable by light microscopy. This study showed that the integrity of the intestinal epithelium was sustained in the intestinal loop model. Despite prominent transcytotic activity and exosome release from the FAE of the ileal PP in sheep, these structures were not associated with transportation of PrPd across the mucosa. The study did not determine how infectivity reaches the follicles of PPs. The possibility that the infectious agent is transported across the FAE remains a possibility if it occurs in a form that is undetectable by the methods used in this study. Infectivity may also be transported via lymph to the blood and further to all other lymphoid tissues including the PP follicles, but the early presence of PrPd in the PP follicles during scrapie infection argues against such a mechanism.

Intestinal lymphangiectasia — a report of two cases

Intestinal lymphangiectasia is a rare benign disease characterised by focal or diffuse dilation of the mucosal, submucosal and subserosal lymphatics. Clinically, the patients may present with protein losing enteropathy (PLE), hypoproteinemic oedema, chylous ascites, pleural effusion, acute appendicitis and intestinal obstruction.

The normal configuration and interindividual differences in intramural lymphatic vessels of the esophagus

Recently, interindividual differences in lymphatic vessel density among patients with cancer have become a focus of interest for surgeons as a significant prognostic factor. Little morphometric information is available about esophageal lymphatics in the absence of esophageal pathologic changes. We used D2-40 immunohistochemical examination to clarify the normal configuration of the esophageal intramural lymphatics and to evaluate morphometrically preexisting mucosal vessels. D2-40 immunohistochemical staining for human lymphatic epithelium was performed at three sites in the cervical and thoracic esophagus in 16 donated cadavers without macroscopic malignancy or chronic inflammation. We determined the total numbers of lymphatic vessels and their complete circumferential lengths. Our immunohistochemical evaluation consistently demonstrated mucosal longitudinal and intermuscular circumferential vessels. In contrast to a previous diagram, the submucosal lymphatics were limited to a few circumferential and marginal vessels. On the basis of these findings, we suggest a new scheme for the intramural lymphatic vessels. In this morphometric study, interindividual differences in number and circumferential length of mucosal lymphatic vessels ranged from 100% to 200% (2-3 times), and site-dependent differences were not evident. After correction for esophageal thickness, interindividual differences in lymphatic vessel density were still 2-fold. We hypothesized that the greater length and number of lymphatic vessels in the lamina propria mucosae are likely to provide greater opportunity for lymphatic vessel invasion of cancer. Thus propensity toward cancer invasion would seem to depend not only on cancer pathology but also on individual anatomic features.

Small Bowel Lymphangioma

Purpose: Mesentric lymphangioma is a rare benign cystic tumor of lymphatics of the bowel. It is usually found in the first decade of life and has a female predominance in adults. It differs from other mesenteric and retroperitoneal cysts, as it is proliferative and invasive in nature. It is usually asymptomatic in adults and found on surgery or autopsy. It rarely presents as occult GI bleed and iron deficiency anemia. We present such a patient in whom capsule endoscopy was diagnostic. Methods: Our patient is a 36 year old female who presented with fatigue, shortness of breath, occassional diffuse abdominal pain, melena and dizziness for 6 months. She denied any nausea, vomiting, hematochezia, NSAID use or family h/o cancer. Labs revealed Hb of 3.7, Hct 12.5, MCV 60.4, Plt 461, WBC 7.2, Iron 2, Ferritin 3, TIBC 367 and positive FOBT x 3. After transfusion of 4 units PRBC, Hb improved to 9.8. Small bowel enteroscopy with biopsies revealed mild antral gastritis, H. pylori negative and normal villous architecture. Colonoscopy was completely normal. Abdominal CT and Small Bowel series showed luminal narrowing and thickening of small bowel loops in left upper quadrant. Patient was given a patency capsule which passed without any complications. Capsule endoscopy revealed a mass like lesion with yellowish – white discoloration with active bleeding in the small bowel. Laparoscopic resection of the lesion showed diffuse dilatation of the mucosal, submucosal and subserosal lymphatics consistent with small bowel lymphangioma. The post operative course was uneventful and patient was discharged. Results: Conclusion: Abdominal lymphangiomas are uncommon benign tumors. The mean age at presentation is 2.2 years with a male predominance. Etiology may be benign proliferation of ectopic lymphatics. 95% of lymphangiomas are found in the neck and axilla and very rarely found in the intestine. Clinical presentation include abdominal pain, distention, fever, and vomiting. There may be features of small bowel obstruction or volvulus. In an Australian study of 416 capsule endoscopies, 27 tumors were identified of which only 1 was a lymphangioma. Plain radiography may demonstrate small-bowel obstruction or noncalcified soft-tissue mass. CT and MRI may show multiloculated fluid-filled masses, thickening of the bowel wall and reveal size of the tumor, characteristics of the cyst wall and location. Capsule endoscopy may lead to earlier detection and treatment and an improved prognosis for patients with these neoplasms. The prognosis of lymphangiomas depends on location and extent of the lesion. Complete resection is the treatment of choice and has an excellent prognosis. The recurrence rate ranges from 0–13.6%. Malignant degeneration to a low-grade sarcoma is rare.

Neuromuscular alterations in the dilated ileum of an adult patient with segmental lymphangiectasia

Intestinal lymphangiectasia is a rare condition, which is characterized by the dilation of small bowel lymphatics and presents with signs and symptoms of protein-losing enteropathy. Some patients have complained of occlusive symptoms attributable to the mechanical obstruction caused by the considerable mucosal edema associated with the lymphatic dilation. On the basis of the hypothesis that alterations in the neuromuscular structures controlling clearance function or gut tone may play a role in ileal dilation, we examined the resected ileum of a 48-year-old male patient with segmental lymphangiectasia histologically, immunohistochemically (for S100 protein, PGP 9.5, Bcl-2, neuron-specific enolase, neurofilaments, synaptophysin, and CD117/C-kit), and by means of electron microscopy. Histology showed pseudocystic dilation of the mucosal, submucosal, and muscular lymphatics with fragmentation of the circular and longitudinal muscle layers. Hardly any neural expression of synaptophysin was observed, but the neural structures were otherwise morphologically normal and reacted normally to the other neural markers. This case shows that neuromuscular alterations can be found in the dilated ileum of patients with segmental lymphangiectasia.

Videocapsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia

We study two authentic cases of protein-losing enteropathy, the diagnosis of which was facilitated using Given M2A videocapsule endoscopy. The first case corresponded to a primary intestinal lymphangiectasia confirmed by jejunum biopsies and the second one to a protein-losing enteropathy with lymphatic abnormalities secondary to a chronic constrictive pericarditis. In the first case, the mucosa of jejunum presented with a diffuse oedematous aspect, whitish villi, white curved lines probably related to submucosal dilated lymphatics and lacteal juice. In the second case, capsule endoscopy showed oedematous aspect of jejunum mucosa associated with white curved lines similar to those observed in the first case. Videocapsule endoscopy is useful in cases of protein-losing enteropathy to identify presence of intestinal lymphangiectasia and to specify their localisation after ruling out other disorders liable to induce protein-losing gastrointestinal syndrome.

Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep

To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut loops were inoculated with a scrapie brain pool homogenate or normal brain or sucrose solution. After surgery, animals were necropsied at time points ranging from 15 min to 1 month and at clinical end point. Inoculum-associated prion protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub-mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in association with dendritic-like cells in the draining lymph nodes at up to 24 h post-challenge. Replication of infection, as demonstrated by the accumulation of disease-associated forms of PrP in Peyer's patches, was detected at 30 days and sheep developed clinical signs of scrapie at 18-22 months post-challenge. These results indicate discrepancies between the routes of transportation of PrP from the inoculum and sites of de novo-generated disease-associated PrP subsequent to scrapie agent replication. When samples of homogenized inoculum were incubated with alimentary tract fluids in vitro, only trace amounts of protease-resistant PrP could be detected by western blotting, suggesting that the majority of both normal and abnormal PrP within the inoculum is readily digested by alimentary fluids.

Bacterial translocation, intestinal ultrastructure and cell membrane permeability early after major liver resection in the rat.

The process and route of bacterial translocation from the gut after major liver resection remain unclear. In the present study enteric bacterial translocation, enterocyte ultrastructure in the ileum and colon, the process and route of bacterial invasion and the permeability of the cell membrane system and blood-tissue barrier were evaluated in rats receiving sham operation, and 70 or 90 per cent hepatectomy. The incidence of bacterial translocation to mesenteric lymph nodes was 80-100 per cent in rats 6 h after 70 per cent and 2-4 h after 90 per cent hepatectomy, and 80-100 per cent to the systemic circulation 2-4 h after 90 per cent hepatectomy but only 20 per cent to the portal vein. An increase in bacterial adherence to the intestinal surface, damage to the permeability of the cell membrane system and blood-tissue barrier, and pathological alterations in the ileum and colon developed, correlating with the extent of liver removed and the time that had passed after hepatectomy. Most translocating bacteria appeared in morphologically intact enterocytes with increased membrane permeability, in antigen-presenting cells and in submucosal lymphatics, but some bacteria were also seen within damaged enterocytes 4h after 90 per cent hepatectomy. These results indicate that altered permeability of the cell membrane system may be one of the earliest characteristics of challenged enterocytes, and that enteric bacteria translocate through both morphologically normal and abnormal enterocytes. Translocation occurred mainly into the lymphatics, bacteria either being 'carried' by antigen-presenting cells or entering by active invasion.

Remission of protein-losing enteropathy after nodal lymphoma treatment in a patient with primary intestinal lymphangiectasia

Primary intestinal lymphangiectasia (PIL), so-called Waldmann's disease, is an uncommon condition, characterized by dilated intestinal submucosal and subserosal lymphatics of the gastrointestinal tract. Protein-losing enteropathy is the most common manifestation of this supposed congenital disease. Since the initial description in 1961, 11 cases of lymphoma have been reported suggesting that PIL predisposes to lymphoma. Here, we report the first case of primary nodal location lymphoma during PIL with recovery of the protein-losing enteropathy after its treatment by radiochemotherapy.

Hepatobiliary and pancreatic: Cholangiocarcinoma with chylous ascites

Chylous ascites is ascitic fluid with a milky appearance that is rich in triglycerides. The disorder is rare, with a reported frequency of 1 in 20 000 hospital admissions. The most common cause is an intra-abdominal malignancy, usually advanced gastric or pancreatic cancer. The typical mechanism involves obstruction or malignant infiltration of lymphatic channels with the subsequent development of a lymphatic fistula that communicates with the peritoneal cavity. Non-malignant causes of chylous ascites include cirrhosis, tuberculosis, filariasis, abdominal trauma, abdominal surgery and abdominal irradiation. In cirrhosis, the mechanism for chylous ascites might involve increases in lymphatic flow leading to increases in pressure and the rupture of small lymphatic channels. The investigations illustrated below were from a 60-year-old woman who presented with epigastric pain, abdominal fullness and weight loss. She had hepatitis C and had previously had a cholecystectomy. A computed tomography scan showed ascites and a mass near the hilum of the liver consistent with cholangiocarcinoma. An ascitic tap revealed milky fluid with a triglyceride level of 285 mg/dL (3.2 mmol/L). Ascitic fluid cytology was positive for malignant cells. Her serum triglyceride level was 60 mg/dL (0.7 mmol/L) and she had an elevated serum concentration of the tumor marker, Ca19.9. An upper gastrointestinal endoscopy showed multiple white dots in the second part of the duodenum (Fig. 1). Histological evaluation of duodenal biopsies revealed mild inflammation and dilated submucosal lymphatics. A lymphangiogram was performed by injecting 99mTc-labeled human serum albumin into both feet. At 10 min, the label was detected in the mid-abdomen (anterior and posterior views) and, at 4 h, there was partial obstruction of abdominal lymphatic channels (Fig. 2). Some of the label leaked into the peritoneal cavity and was subsequently absorbed into the general circulation. An autopsy at 5 months after the initial presentation confirmed the presence of widespread cholangiocarcinoma.