Monday, August 20, 2007

The role of immune system in colon metastasis. Lymphanogiogenesis or lymphedema in cancer tissue

The role of immune system in colon metastasis. Lymphanogiogenesis or lymphedema in cancer tissue

Pol Merkur Lekarski. 2007 May

[Article in Polish]
Stańczyk M, Olszewski WL, Gewartowska M, Maruszyński M.
Zakład Chirurgii Transplantacyjnej, IMDiK PAN w Warszawie.
ms@cmdik.pan.pl

The extent of lymph node metastasis is a major determinant for the staging and the prognosis of most human malignancies. Although the clinical significance of lymph node involvement is well documented, molecular mechanisms that promote tumor spread into the lymphatic or blood vascular systems and widespread dissemination are not well understood.

Although there is a large body of evidence that newly visualized lymphatics facilitate formation of metastases, it remains unclear whether these are "new" or simply pre-existing dilated vessels. High level of permeability of tumor blood capillaries brings about high tissue fluid and lymph formation. The physical forces but not the putative cancer-produced VEGF C may be responsible for more lymphatics seen around cancer than in normal tissue.

The main question to be answered is: are there morphologic and functional differences between newly formed and pre-existing intra- or peri-tumoral lymphatics? In our experience specimens of gastric and colon cancer revealed presence of peri-tumoral but not intra-tumoral lymphatics. Tumor tissue contained numerous tissue fluid "lakes" communicating with lymphatics.

We speculate that increased production of lymph in the tumor tissue caused by high blood capillary permeability brings about dilatation of the interstitial space and peri-tumoral lymphatics. Excessive lymph flow may drag tumor cells. This article is reviews current literature on the role of angiogenesis and lymphangiogenesis in cancer metastasis with respect to own research.

PMID: 17679395 [PubMed - in process]

Friday, August 03, 2007

The Thoracic and Abdominal Lymphatics Abstracts

The Thoracic and Abdominal Lymphatics Abstracts

Lymphatic drainage between thorax and abdomen: please take good care of this well-performing machinery...

Acta Clin Belg Suppl. 2007

ZiekenhuisNetwerk Antwerpen, Campus Stuivenberg, Intensive Care Unit, Antwerp, Belgium
.
manu.malbrain@skynet.be

INTRODUCTION: Patients with sepsis often receive large amounts of fluids and the presence of capillary leak, trauma or bleeding results in ongoing fluid resuscitation. This increases interstitial and intestinal edema and finally leads to intra-abdominal hypertension (IAH), which in turn impedes lymphatic drainage. Patients with IAH often develop secondary respiratory failure needing mechanical ventilation with high intrathoracic pressure or PEEP that might further alter lymphatic drainage. This review will try to convince the reader of the importance of the lymphatics in septic patients with IAH.

METHODS: A Medline and PubMed literature search was performed using the terms "abdominal pressure", "lymphatic drainage" and "ascites formation".The references from these studies were searched for relevant articles that may have been missed in the primary search. These articles served as the basis for the recommendations below.

RESULTS: Induction of sepsis with lesion of the capillary alveolar barrier results in an increased water gradient between the capillaries and the interstitium in the lungs. The drainage flow to the thoracic duct is initially increased in order to protect the Lung and maintain the pulmonary interstitium as dry as possible, however this results in increased intrathoracic pressure. Sepsis also increases the permeability of the capillaries in the splanchnic beds. In analogy to the lungs the lymphatic flow in the splanchnic areas increases together with the pressure inside as a physiological response in order to limit the increase in IAP. At a critical IAP level (around 20 cmH2O) the lymph flow starts to decrease and the splanchnic water content progressively increases.The lymph flow from the abdomen to the thorax is progressively decreased resulting in increased splanchnic water content and ascites formation. The presence of mechanical ventilation with high PEEP reduces the lymph drainage further which together with the increase in IAP decreases the lymphatic pressure gradient in the splanchnic regions, with a further increase in water content and IAP triggering a vicious cycle.

CONCLUSION: Although often overlooked the role of lymphatic flow is complex but very important to determine not only the fluid balance in the lung but also in the peripheral organs. Different pathologies and treatments can markedly influence the pathophysiology of the lymphatics with dramatic effects on endorgan function.

PMID: 17469714
[
PubMed - indexed for MEDLINE]

Lymphatic drainage of the peritoneal space: a pattern dependent on bowel lymphatics.


Parungo CP, Soybel DI, Colson YL, Kim SW, Ohnishi S, DeGrand AM, Laurence RG, Soltesz EG, Chen FY, Cohn LH, Bawendi MG, Frangioni JV. Department of Surgery, Brigham & Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. John V. Frangioni Email: jfrangio@bidmc.harvard.edu Dr. Parungo was the recipient of an award at the SSO meeting.

Keywords: Peritoneal space - Lymph node - Lymphatic drainage - Near-infrared fluorescence - Carcinomatosis - Metastasis

BACKGROUND: Understanding lymph drainage patterns of the peritoneum could assist in staging and treatment of gastrointestinal and ovarian malignancies. Sentinel lymph nodes (SLNs) have been identified for solid organs and the pleural space. Our purpose was to determine whether the peritoneal space has a predictable lymph node drainage pattern.

METHODS: Rats received intraperitoneal injections of near-infrared (NIR) fluorescent tracers: namely, quantum dots (designed for retention in SLNs) or human serum albumin conjugated with IRDye800 (HSA800; designed for lymphatic flow beyond the SLN). A custom imaging system detected NIR fluorescence at 10 and 20 minutes and 1, 4, and 24 hours after injection. To determine the contribution of viscera to peritoneal lymphatic flow, additional cohorts received bowel resection before NIR tracer injection. Associations with appropriate controls were assessed with the chi(2) test.

RESULTS: Quantum dots drained to the celiac, superior mesenteric, and periportal lymph node groups. HSA800 drained to these same groups at early time points but continued flowing to the mediastinal lymph nodes via the thoracic duct. After bowel resection, both tracers were found in the thoracic, not abdominal, lymph node groups. Additionally, HSA800 was no longer found in the thoracic duct but in the anterior chest wall and diaphragmatic lymphatics.

CONCLUSIONS: The peritoneal space drains to the celiac, superior mesenteric, and periportal lymph node groups first. Lymph continues via the thoracic duct to the mediastinal lymph nodes. Bowel lymphatics are a key determinant of peritoneal lymph flow, because bowel resection shifts lymph flow directly to the intrathoracic lymph nodes via chest wall lymphatics.

Springerlink

Lymphatic drainage of the diaphragmatic pleura to the peritracheobronchial lymph nodes.

Surg Radiol Anat. 2003 Apr Okiemy G, Foucault C, Avisse C, Hidden G, Riquet M. Laboratoire d'Anatomie, UFR de Médecine, Reims, France.

Keywords: Diaphragm, Pleural lymphatics, Mediastinum, Lymph node, Lung cancer

Non-small cell lung cancer invading the visceral pleura is characterized by a particular richness of mediastinal lymph node (LN) metastases. This may be due to subpleural lymphatic drainage of tumor cells. The aim of this study was to determine mediastinal LN lymphatic drainage from the diaphragmatic pleura. Subpleural lymphatics of 30 adult cadavers and 12 fetuses were injected with a modified Gerota's medium to permit lymph vessels and nodes to be visualized and then dissected. Each stage of the dissection was described and photographed.

In 32 cadavers mediastinal visceral LN chains were injected, of which 29 originated from the mediolateral portion of the diaphragm. On the right, injections (n=16) demonstrated lymph vessels (n=20) ascending directly along the inferior pulmonary ligaments (n= or after having encircled the inferior vena cava (n=, and lymph vessels passing between the pulmonary veins (n=4); all these lymphatics were connected to the intertracheobronchial nodes and some ascended along the tracheobronchial LN chains in the upper mediastinum.

On the left, injections (n=13) demonstrated lymph vessels (n=16) ascending along the inferior pulmonary ligament (n=5) or along the esophagus (n=11) and connecting to the intertracheobronchial nodes, some of which ascended further in the upper mediastinum (left paratracheobronchial LN chain).

These mediastinal LN chains are the same as those that receive lymph from the pulmonary segments. Lymphatic drainage of the diaphragmatic pleura may add to that of the lung involved in cancer and potentially increases lymphatic spread of tumor cells.

Springerlink

Renal lymphatic drainage and thoracic duct connections: implications for cancer spread.

Lymphology.

2006 Mar Assouad J, Riquet M, Foucault C, Hidden G, Delmas V. Service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, and Institut d'Anatomie, Biomédicale des Saints-Pères, Paris, France.

Studies on renal lymph drainage have generally described lymph nodes without further investigation of the lymph vessels. Our purpose was to revisit this organ to study the vessel drainage pattern. This investigation was performed on 16 refrigerated adult cadavers. After both kidneys were injected with a blue modified Gerota mass, lymph vessels were dissected until their termination. From the right kidneys (n = 13), lymphatics (n = traveling on the anterior aspect of the inferior vena cava were dissected, reaching interaortocaval and more distant nodes, aorta bifurcation (n = 1) and left lateroaortic (n = 1); posterior lymphatics were observed in all subjects, uniformly connecting to the thoracic duct, either after crossing nodes (n = or directly (n = 5). From the left kidneys (n = 13), anterior efferents (n = 16) were dissected, reaching left lateroaortic and also celiac (n = 4) and iliac (n = 1) nodes; posterior lymphatics were also demonstrated, always connecting to the thoracic duct (3 directly). Renal lymphatics have been found to reach very distant nodes as well as always connecting to the origin of the thoracic duct. This feature suggests an important role in both the formation of the thoracic duct and in the spread of renal cancer.

PMID: 16724507 [PubMed - indexed for MEDLINE]

Regional recruitment of rat diaphragmatic lymphatics in response to increased pleural or peritoneal fluid load

J Physiol. 2007 Mar

Moriondo A, Grimaldi A, Sciacca L, Guidali ML, Marcozzi C, Negrini D. Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, Via J.H. Dunant 5, 21100 Varese, Italy. Corresponding author D. Negrini: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, Via J.H. Dunant 5, 21100 Varese, Italy.Email: daniela.negrini@uninsubria.it

The specific role of the diaphragmatic tendinous and muscular tissues in sustaining lymph formation and propulsion in the diaphragm was studied in 24 anaesthetized spontaneously breathing supine rats. Three experimental protocols were used: (a) control; (b) peritoneal ascitis, induced through an intraperitoneal injection of 100 ml kg(-1) of iso-oncotic saline; and (c) pleural effusion, induced through an intrapleural injection of 6.6 ml kg(-1) saline solution. A group of animals (n = 12) was instrumented to measure the hydraulic transdiaphragmatic pressure gradient between the pleural and peritoneal cavities in the three protocols. In the other group (n = 12), the injected iso-oncotic saline was enriched with 2% fluorescent dextrans (molecular mass = 70 kDa); at 30 min from the injections these animals were suppressed and their diaphragm excised and processed for confocal microscopy analysis. In control conditions, in spite of a favourable peritoneal-to-pleural pressure gradient, the majority of the tracer absorbed into the diaphragmatic lymphatic system converges towards the deeper collecting lymphatic ducts. This suggests that diaphragmatic lymph formation mostly depends upon pressure gradients developing between the serosal cavities and the lymphatic vessel lumen. In addition, the tracer distributes to lymph vessels located in the muscular diaphragmatic tissue, suggesting that active muscle contraction, rather than passive tendon stretch, more efficiently enhances local diaphragmatic lymph flow. Vice versa, a prevailing recruitment of the lymphatics of the tendinous diaphragmatic regions was observed in peritoneal ascitis and pleural effusion, suggesting a functional adaptation of the diaphragmatic network to increased draining requirements.

Abstract