Surgical Removal Of Lymph Nodes Research Articles

Analysis of effect of colonoscopy combined with laparoscopy in the treatment of colorectal tumors.

Colorectal cancer is one of the most common digestive tract tumors. To evaluate the feasibility and safety of laparoscopic colorectal cancer surgery. This study retrospectively analyzed early postoperative clinical data of 48 patients with colorectal cancer treated in our hospital between 2015 and 2021, of which 21 underwent laparoscopic colorectal surgery, and 27 underwent laparotomy. There was no significant difference in clinical data. Patients were included if they had colorectal cancer (confirmed by colonoscopy and biopsy pathological examination before surgery), were evaluated for possible radical surgery before surgery, and had no intestinal obstruction, tumor invasion of adjacent organs (by digital rectal examination and preoperative abdominal color Doppler ultrasound, CT confirmed) and no other history of abdominal surgery. Using the method of clinical control study, operation time, intraoperative blood loss, postoperative general condition, surgical lymph node removal (postoperative pathology), surgical complications, gastrointestinal function recovery, surgical before and after blood glucose, body temperature, white blood cells, pain visual analog scale (VAS) and other conditions were compared and analyzed to determine feasibility and safety of laparoscopic surgery for colorectal cancer. Colorectal cancer was successfully removed by laparoscopic radical resection without any significant problems or surgical fatalities. Age, gender, tumor location, stage, and duration of surgery did not differ between laparoscopic and laparotomy operations. Compared to laparotomy, postoperative eating, bowel movements, and blood sugar levels improved. Variations in the length of surgically removed specimens after VAS measurements revealed open and laparoscopic operations. The overall lymph node count was 10.8 ± 1.6, with no variation between the two techniques. Laparoscopic colorectal cancer radical surgery is safe and feasible. Also, it has the advantages of minimally invasive surgery. Laparoscopic colorectal cancer radical surgery can comply with the principles of oncology revolutionary.

Red Out: Bleeding During Robotic Retroperitoneal Lymph Node Dissection and Strategies To Manage It

Robotic retroperitoneal lymph node dissection is emerging as an attractive minimally invasive technique to remove residual and recurrent retroperitoneal masses in patients with germ cell malignancies. It has huge potential benefits for patients in terms of lower rates of blood loss, ileus, postoperative pain, and scarring, and faster return to full activity. Inadvertent injury to the great vessels, lumbar tributaries, and other vessels is not uncommon and requires a calm but strategic management response. A thorough knowledge of the standard anatomy, specific pathology, and anatomic variations will help robotic surgeons in managing intraoperative haemorrhage. We describe the anatomy of the retroperitoneal vessels, surgical case selection, and the technical and nontechnical skills essential for success in this complex and high-risk procedure. Patient summaryRobot-assisted surgical removal of lymph nodes from the area behind the abdominal cavity is a complex operation that has minimal bleeding if all goes well. However, as it involves operating on the major abdominal blood vessels, there is a risk of life-threatening bleeding that the operating team must be able to rapidly control. Effective teamwork and a range of advanced technical skills are required to respond to any serious bleeding.

Veterinary approaches to canine mammary tumors and knowledge of the consensus statement in Brazil

Mammary gland tumors are one of the most commonly diagnosed tumors in female dogs, with a reported prevalence ranging from 26 to 73% in Brazil. In recognition of the importance of these tumors veterinary researchers and clinicians in Brazil produced the first consensus statement regarding canine mammary tumors in 2010. The intention was to establish criteria for diagnosis, prognosis, and treatment. This study evaluated the methods of prevention, diagnosis, treatment, and determination of prognosis used by veterinarians in Brazil, and sought to quantify the number of veterinarians who were aware of the consensus statement. One hundred and three veterinary clinics participated in the study, 87.37% of which recommend early neutering as a preventative treatment for mammary tumors. For diagnosis, 100% of these use laboratory testing, 94.17% perform chest radiography, 78.64% incisional biopsies, 44.66% cytological analysis, and 13.59% immunohistochemical analysis. The most common surgical procedure is unilateral mastectomy (72.81%), and chemotherapy is performed in 49.51% of the clinics. Of the 103 clinics, 66.01% were aware of the consensus. Although knowledge of the consensus statement is widespread among veterinarians in Brazil, not all its recommendations are being followed. Preventive actions for canine mammary tumors are well established in most parts of the country. However, the consensus statement has had little influence on informing prognostic and therapeutic approaches, with a poor uptake of surgical removal of lymph nodes and immunohistochemical examination.

Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol.

Correctly identifying nodal status is recognized as a critical prognostic factor in many cancer types and is essential to guide adjuvant treatment. Currently, surgical removal of lymph nodes followed by pathological examination is commonly performed as a standard-of-care to detect node metastases. However, conventional pathology protocols are time-consuming, yet less than 1 % of lymph node volumes are examined, resulting in a 30-60 % rate of missed micrometastases (0.2-2 mm in size). This study presents a method to fluorescently stain excised lymph nodes using paired-agent molecular imaging principles, which entail co-administration of a molecular-targeted imaging agent with a suitable control (untargeted) agent, whereby any nonspecific retention of the targeted agent is accounted for by the signal from the control agent. Specifically, it was demonstrated that by dual-needle continuous infusion of either an antibody-based imaging agent pair (epidermal growth factor receptor (EGFR) targeted agent: IRDye-800CW labeled Cetuximab; control agent: IRDye-700DX-IgG) or an Affibody-based pair (EGFR targeted Affibody® agent: ABY-029; control agent IRDYe-700DX carboxylate) at 0.3 ml/min. The results demonstrated the possibility to achieve >99 % sensitivity and > 95 % specificity for detection of a single micrometastasis (~0.2 mm diameter) in a whole lymph node within 22 min of tissue processing time. The detection capabilities offer substantial improvements over existing intraoperative lymph node biopsy methods (e.g., frozen pathology has a micrometastasis sensitivity <20 %).

Breast Cancer and Lymphedema: A Narrative Review

Breast cancer is the second most common cancer diagnosed worldwide, and the leading cause of cancer death in women. The understanding of disease presentation by patients and health care providers is crucial for a correct diagnosis and management. Preventive measures emphasize risk-reducing behaviors such as a healthy diet, reduced alcohol consumption, increased physical activity, and breastfeeding children. Screening techniques such as mammography, ultrasound, and MRI aid in early detection. Following the screening, a breast biopsy is performed, and a histopathological assessment is carried out to confirm a breast cancer diagnosis. In addition to surgery, radiotherapy, and lifestyle modifications, treatment regimens include a range of medications such as anti-hormonal drugs and chemotherapy. Lymphedema is a severe and major long-term consequence of breast cancer treatment. The major contributors to the diminished lymph drainage are a lumpectomy/mastectomy procedure that involves the surgical removal of lymph nodes, and radiotherapy. The fluid accumulation of lymphedema poses physical limitations to the patient and impacts the overall quality of life. A sentinel lymph node biopsy is an essential method of identifying the first draining lymph nodes affected by metastasis. This procedure allows surgeons to later remove only affected lymph nodes, sparing those that are unaffected and hence reduce the risk and magnitude of lymphedema development. Patients who receive education about lymphedema demonstrate higher compliance with treatment and self-care management practices. The purpose of this review is to provide information about breast cancer, the development of lymphedema, and how to recognize and manage both.

Ultra-Sensitive Detection and Inhibition of the Metastasis of Breast Cancer Cells to Adjacent Lymph Nodes and Distant Organs by Using Long-Persistent Luminescence Nanoparticles

The metastasis of breast cancer mainly occurs through the axillary lymph node and blood circulation systems. It is extremely difficult to know when the cancer cells start to metastasize; however, early detection of breast cancer metastasis is crucial and challenging to enable surgical removal of the primary tumor and perform a systematic lymphadenectomy to eliminate invasion of the tumor. Herein, we report real-time tracking of the metastasis of orthotopic breast cancer with background-free near-infrared long-persistent luminescence (NIR-PL) imaging, and its guidance for the surgical removal of lymph nodes. The NIR-PL imaging is based on Cr3+/Nd3+ codoped ZnGa2O4 (A-ZGCN) nanoparticles with a superlong afterglow time of more than 15 days. We show that the detection sensitivity of metastasis of cancer cells with the NIR-PL imaging is higher than the classic bioluminescence imaging. We find that the metastasis of breast cancer cells to lymph nodes occurred as early as on the third day after orthotopic inoculation of breast cancer cells and followed an order of the proper axillary lymph node (PALN, day 3) > accessory axillary lymph node (AALN, day 6) > accessory mandibular lymph node (AMLN, day 9) > mandibular lymph node (MLN, day 25). In addition, we show that the NIR-PL nanoprobes (i.e., A-ZGCN NPs) displayed 17% radioenhancement, which was used for radiotherapy of orthotopic breast cancer to further prevent and reduce its metastasis to other organs. The radiotherapy treatment is superior to surgery for removal of the tumor accompanied by a NIR-PL imaging-guided lymphadenectomy. Our work demonstrates the great potential of NIR-PL imaging and the corresponding nanoprobes for tracking metastasis of cancer cells and for radiotherapy.

Lymphatic Endothelial Cells under Mechanical Stress: Altered Expression of Inflammatory Cytokines and Fibrosis.

Secondary lymphedema, resulting from damage to lymphatic vessels, is a common sequela following surgical removal of lymph nodes for cancer. Current therapeutics for treating lymphedema are limited and further research on underlying causes is warranted. Published studies on molecular mechanisms of lymphedema primarily focus on lymphatic endothelial cells (LECs), which comprise the innermost lining of lymphatic capillaries and collecting vessels. However, traditional static culture of LECs may not adequately recapitulate the lymphedemous cell phenotype as transcriptomal comparison of human dermal LECs has shown significant differences in ex vivo and in vitro LEC gene expression. In this study, we designed a dynamic culture system, in which LECs were exposed to physiologic and excess mechanical strain to determine if native and lymphedemous phenotypes could be reproduced in vitro. Purified human LECs were cultured in silicon dishes and subjected to 0% (control), 4%, and 8% mechanical strain for 72 hours. Our results indicate that control and stretched LECs maintained a mature phenotype. Extreme stretching at 8% strain significantly increased LEC proliferation and significantly increased Prox1 expression, suggesting a lymphedemous cell phenotype resulting with lymphangiogenesis. Mechanical strain reinforced a mature lymphatic phenotype and excess strain promoted lymphangiogenesis, while altering collagen deposition and cytokine secretion.

Clinical and Morphological Features of Different Variants Castleman's Disease

Background: Castleman' s disease (CD) is rare lymphoproliferative disorder with long asymptomatic current and high risk of transformation in malignant lymphoma. For last years, diagnostics of CD improved and uniform classification of an illness was accepted. Depending on morphological features allocate 3 variant of CD: hyaline-vascular (HVV), plasma cell (PCV) and mixed cell. Most cases of the ÑD involve a single or localized group of lymph nodes and can be asymptomatic. In these cases the histologic picture can be characterized as a HVV or mixed cell and PCV morphology. Less often the disease proceeds with multiple lymphoid regions (multicentric CD, MCD) and is usually accompanied by various systemic inflammatory symptoms (fever, weight loss and night sweats). In these cases histologic picture in the involved lymph nodes meet mix cell or PCV of CD. The role of a human herpes virus-8 (HHV-8) in pathogenesis of MCD is studied. It is known that HHV-8 codes in a genome of a cell of the person some regulatory proteins and cytokines, first of all a virus homolog interleukin-6 which stimulates development of human IL-6 and endothelial factor of growth that conducts to a neoangiogenesis in not tumoral lymph nodes. HHV-8-positive MCD allocate separately in due to its extremely aggressive course and a high risk of transformation into HHV-8-positive plasmablastic lymphoma.Aim: Explore the features of a clinical current and of therapeutic approaches at different variants CD.Patients and Methods: In Center for Hematology since 1996 to the present time observed clinical and morphological features of 76 pts with CD. Clinical data were obtained during the retrospective analysis of 17 outpatient clinical records and prospective supervision over 59 pts. The diagnosis was established from results of histological and immunohistochemical examinations of removed lymph nodes in all cases. Frequency analyses were performed using z-tests with SAS 9.1 software.Results: HVV with local lymph nodes involvement was diagnosed in 38 (50%) pts. The average age of pts was 40 years The PCV was also observed in 38 (50%) cases, among them in 17 (22%) pts were found to have local involvement and 21 (28%) had multicentric involvement. Five (24%) pts with MCD were established to be infected with human herpesvirus type 8. Male (37 pts) and female (39 pts) are suffering with an identical frequency. However, HVV is more often diagnosed for female, than at male (71% to 29% respectively), PCV equally often meets both at male, and at female (47% of male, 53% of female) and, at last, at MCD the share of male statistically significantly is more than share of female (86% against 14%, p=0,05) (Figure 1). The basic involvement areas in local HVV and PCV were peripheral (38%), mediastinal (29%), retroperitoneal (18%) abdominal (9%) and small pelvic (6%) lymph nodes (95% CI). Local HVV and PCV proceed benign and in 94.5% of cases are cured by surgical removal of lymph nodes involved in the pathological process, in 5.5% of cases with inoperable cases require followed by radiation therapy. MCD was significantly more common in male, occurs aggressively with severe constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, autoimmune hemolysis, thrombocytopenia, and involvement of extranodal foci in the pathological process. MCD transformation to plasmoblastic lymphoma was observed in 4 of 5 HHV8-positive pts and followed by a poor outcome. The prognosis of untreated MCD was unfavorable. In a number of cases prednisolone monotherapy worsened and the MCD pts receiving timely R-CHOP or R-VD chemotherapy could achieve sustained remission (the 5-year OS was 55%).Conclusion: The prognosis of HVV and local PCV is favorable: the disease is surgically cured in 95% of cases. Chemotherapy according to the program of Non-Hodgkins Lymphomas indicated for the treatment of MCD: sustained remission can be achieved by the use of R-CHOP or R-VD programs. HHV8-positive MCD characterized by high risk disease transformation to incurable plasmablastic lymphoma. Overall, prognosis and therapy choice in HIV-negative pts with CD depend on the histological type of the disease, the extent of a tumor and HHV-8 infection. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract 2791: Genetic variations associated with breast cancer-related lymphedema in a prospective multiethnic cohort

Abstract Background: Lymphedema is a common chronic condition secondary to surgical removal of lymph nodes in breast cancer (BC) patients. Currently, there is no cure for breast cancer-related lymphedema (BCRL), and early diagnosis is critical for symptom management. Because primary lymphedema is hereditary, genetic variations may predispose BC patients to secondary BCRL and may thus be predictive markers for risk stratification. Methods: In this analysis of 2,756 participants in the Pathways Study, a prospective cohort of BC survivors, we analyzed 134 single nucleotide polymorphisms (SNPs) selected to represent common variations in 8 genes implicated in primary lymphedema (VEGFC, VEGFD, FLT4, GJA12, FOXC2, CCBE1, GATA2 and SOX18). Up to 48 months post-BC diagnosis, 324 women reported development of BCRL. We derived hazard ratios (HR) and 95% confidence intervals (CI) of BCRL for each SNP, under additive genetic effects from Cox proportional hazards models adjusting for genetic ancestry and known BCRL risk factors, including age at BC diagnosis, BMI, physical activity, and clinical factors. Analyses were performed separately in each of four racial/ethnic groups (European American (EA) (n = 1,789), African American (AA) (n = 208), Asian (n = 344), Hispanic (n = 344)). Results: Among EA women, the most significant SNP associated with BCRL was an intronic variant, rs11659526 in CCBE1. Each copy of the variant C allele was associated with a 27% reduced multivariable-adjusted hazard of BCRL (HR = 0.73, 95% CI: 0.57-0.92, p = 0.009). Two other SNPs in CCBE1 were also associated with risk of BCRL (p&amp;lt;0.05). Other SNPs in CCBE1 were significantly associated with BCRL risk in the three minority groups: 7 in AA women, 2 in Asian women, and 9 in Hispanic women, but with essentially no SNP overlap across the four groups. SNPs in several other genes were also significantly associated with BCRL risk in minority groups, including GATA2 and VEGFC in AAs, FLT4 and FOXC2 in Asians, and VEGFC and VEGFD in Hispanics. Most associations remained unchanged after excluding BCRL within 6 months after BC diagnosis. As SNPs were selected for a priori hypotheses from associations with primary lymphedema, these associations were not adjusted for multiple testing. However, in conservative analyses to account for multiple testing, associations were no longer statistically significant. Conclusion: To our knowledge, this is the largest genetic association study of BCRL conducted to date. We found that SNPs in genes previously implicated in hereditary primary lymphedema, including CCBE1, were associated with BCRL, suggesting common biological mechanisms underlying primary and secondary lymphedema. The relatively small sample sizes for minority groups and moderate significance level of the associations points to the need for future replication in independent studies and the potential search for additional genes at a genome-wide level. Citation Format: Song Yao, Yali Zhang, Valerie S. Lee, Janise M. Roh, Isaac J. Ergas, Lwarence H. Kushi, Christine B. Ambrosone, Marilyn L. Kwan. Genetic variations associated with breast cancer-related lymphedema in a prospective multiethnic cohort. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2791. doi:10.1158/1538-7445.AM2015-2791

167. Immune checkpoints in breast cancer surgery

167. Immune checkpoints in breast cancer surgery

Radiographic extracapsular extension (ECE) and treatment outcomes in locally advanced oropharyngeal carcinoma (OPC).

6019 Background: Pathologic ECE (pECE) of tumor through lymph node (LN) is a poor prognosticator for OPC and typically diagnosed upon surgical LN removal. At our institution, experienced radiologists routinely identify ECE on pretreatment CT. The prognostic value of radiographic ECE (rECE) is less clear and may prove clinically useful. In this study, we evaluate rECE as an independent prognosticator in OPC. Methods: Retrospective review of 185 patients with locally advanced OPC treated in our department from 2006-2012. 109 patients had accessible pretreatment CT reports clearly stating the presence or absence of rECE. Patients were treated with definitive concurrent chemoradiation therapy (CCRT) (30%), induction chemo then CCRT (47%), or surgery with adjuvant CCRT (14%) or RT (9%). Kaplan-Meier survival analysis compared these cohorts for locoregional control (LRC), distant control (DC), and progression-free (PFS) and overall survival (OS); log-rank tests were performed for significance. Multivariate analysis was conducted via cox-regression. Results: Median follow-up of the 109 patients was 31 months (range: 1-80 months). 61 patients had rECE(+) and 48 had rECE(-) scans. There was no significant difference between the cohorts in terms of median age, stage, treatment type, smoking history, or tumor HPV status. There was a difference in nodal stage with 83% of rECE(+) patients having N2-3 disease versus 67% of rECE(-) patients (p=0.02). On univariate analysis, there were differences between the rECE(-) versus rECE(+) cohorts in OS (4yr: 92% vs 72%, p=0.01), PFS (4yr: 92% vs 62%, p=0.002), and DC (4yr: 98% vs 76%, p=0.006), with no difference in LRC (4yr: 95% vs 91%, p=0.35). On multivariate analysis factoring in age, smoking history, stage, and treatment type, rECE presence was a negative predictor of OS (hazard ratio, 0.26; 95% CI, 0.07 to 0.95) and PFS (hazard ratio, 0.23; 95% CI, 0.06 to 0.81), with DC approaching significance (hazard ratio, 0.13; 95% CI, 0.02 to 1.05). Conclusions: While pECE is an established risk factor for locally advanced OPC, this study suggests that rECE may be an independent poor prognosticator of PFS, OS and DC with potential importance in guiding clinical management.

Research on Quality of Attachment in Women with Breast Cancer

Analysis of quality of attachment of women with breast cancer within 1 year after initial diagnosing and subsequent treatment was performed in the article by means of the Measure of Attachment Qualities (MAQ) scale (Carver, 1997). 41 women of Bulgarian origin at an average age of 35.25 years (at least 18 and 69 at the most) in stage I, II and III of the disease progress were studied. For the specific sample, the reliability of 4 scales (secure, avoidant, ambivalent-worried and ambivalent-merging attachment) was presented. The quality of attachment was analysed by: 1) medical characteristics (partial or total surgery, surgical removal of lymph nodes, presence or absence of metastases in them), 2) classical therapies (chemotherapy, radiation therapy and hormonal therapy) administered or not and 3) application or not of alternative therapies (herbal medicine, physical load, administration of massage, lymph drainage, use of nutritional supplements, observance of diet). Language: Bulgarian

Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.

Unicentric Castleman’s Disease Presenting With Multiple Enlarged Lymph Nodes In Mediastinum

A case of unicentric Castleman’s disease located in the mediastinum is presented. A 20 years old male suffering from cough had an image of right hilar enlargement on chest X-ray. Thorax CT revealed multiple enlarged lymph nodes both in right paratracheal and hilar region. Radionuclide accumulation was detected by 67 Ga scintigraphy. Surgical removal of lymph nodes at paratracheal region was performed by mediastinoscopic excision and reported as reactive hyperplasia. Lymph nodes located in right hilum was excised by thoracotomy and histopathologic examination confirmed Castleman’s disease. Our thought about this case was a dominant infiltrative mass with an associated lymphadenopathy. 67 Ga scintigraphy imaging that we performed in

Lymphatic Interrupted: Do We Really Understand the Risks and Consequences?

Lymphedema remains one of the most feared complications of breast cancer therapy, yet at the same time, is arguably one of the least well understood. Review of the literature reveals inconsistencies in defining and measuring this condition, as well as in understanding the extent of lymphedema that is clinically significant. The true incidence of lymphedema is widely debated, as are the risk factors leading to its development. The surgical removal of lymph nodes and disruption of lymphatic channels during dissection of the axilla clearly contribute, but there are other variables that play a role, including treatment-related variables such as use of radiation therapy, and patientrelated variables. Some of the most frequently reported patient-related factors are increasing age, higher body mass index, and weight gain. Although infection and injury have been reported to be inciting events in the development of lymphedema, these relationships are less clear. 1,2

Regional Lymph Node Metastases; a Singular Manifestation of the Process of Clinical Metastases in Cancer: Contemporary Animal Research and Clinical Reports Suggest Unifying Concepts

Research results from laboratory animals and human clinical reports provide insight into cancer cell disseminations and elaborate the complex metastatic cascade of cells into both regional lymph nodes and other distant organs. Critical appraisal of clinical trials indicates that lymph node metastases are themselves non-lethal, but indicate prognosis, confirming laboratory conclusions. Distant vital organ metastases can be resected with long term survival in highly selective situations, demonstrating metastatic specificity in oligometastatic disease. Appreciating lymphatic system embryology, anatomy, and physiology is necessary for understanding lymph node metastases. The primary lymphatic system function was to return interstitial fluid to the circulation. Later evolutionary insertion of lymphocyte collections in lymph nodes interrupting lymph flow completed a system of analyzing external antigens to enable adaptive immunologic responses. Human cancers seldom elicit major immunological responses; they are not generally "foreign" enough. Therefore, lymphatic metastases have little meaning in evolutionary terms. Organ specificity of both lymphatic and distant metastases occurs as metastatic cells lie dormant, but grow selectively only in liver, lung, bone, or lymph nodes. These organ specific metastatic cells have little ability to produce different organ site clinical metastases. Thus, laboratory findings and clinical correlations emphasize that surgical lymph node removal should be de-emphasized or omitted. More physiological approaches to the highly manipulable multi-step processes of clinical metastases arising from host microenvironments will eventually prevail.

Vascularized Lymph Node Transplantation Induces Graft-Versus-Host Disease in Chimeric Hosts

The role of lymph nodes (LNs) in adaptive immune responses has been the subject of extensive research. In previous studies, the surgical removal of lymph nodes from rat hind limbs prevented the development of lethal graft-versus-host disease (GVHD) after allogeneic hind limb transplantation to chimeric recipient rats. The purpose of this study was to establish the role of the cellular fraction versus the microenvironment of LNs in the development of GVHD in this model. A rat model for vascularized LN transplantation was developed and graft-versus-host responses were compared after: 1) naive ACI LN cells were infused into Wistar-Furth (WF) rats as chimeric recipients (e.g. [ACI-->WF]); 2) vascularized WF lymph nodes were transplanted to syngeneic WF recipients; 3) nonvascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients; 4) vascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients. Transplantation of vascularized ACI lymph nodes to [ACI-->WF] chimeric recipient rats resulted in severe and sometimes lethal GVHD. In contrast, neither the infusion of purified ACI LN cells nor the transplantation of nonvascularized LNs led to GVHD in chimeric recipients. When introducing allogeneic cells into chimeric recipients, concomitant transplantation of the vascularized LN microenvironment makes a manifest difference between induction and absence of GVHD. This illustrates the important role of the LN microenvironment in adaptive immune responses.

First results for resetting the antitumor immune response by immune corrective surgery in colon cancer

BACKGROUND: A critical step for cancer recurrence is the failure of the cellular immune response. It is suspected that chronic humoral immune responses against some tumor-associated antigens (TAA) can contribute to that failure. METHODS: In this study, we tested the ability of an immune corrective surgical procedure to prevent recurrences of colon cancer in stages I, II, and III. Radiolabeled anti-TAG antibodies injected intravenously become concentrated on TAG-72 immune complexes presented by follicular dendritic cells, which are responsible for the persistent humoral response against TAG-72 TAA. Using a hand-held gamma probe, we can intraoperatively detect and remove lymph nodes involved in TAG-72 presentation. By removing these lymph nodes, together with the tumor tissue, presentation and source of TAG-72 are drastically reduced. RESULTS: The impact of this TAA suppression on the tumor recurrence process is analyzed in a sample of 24 patients. The immune corrective surgical procedure did not increase morbidity. Five years after surgery the following were disease free: 5 of 5 stage I, 6 of 6 stage II, and 10 of 13 stage III. The global survival of this group was 87.5%. Compared with the standard surgical treatment of colon cancer (58% survival for the same stages), this surgical immune corrective procedure introduces a statistically significant improvement of 29% ( P <0.001). CONCLUSIONS: The surgical removal of lymph nodes involved in the persistent humoral immune response against TAA has an important beneficial impact on colon cancer treatment.

Indications and risks of manual lymph drainage in head-neck tumors

Secondary lymphedema of the head and neck can develop as a result of obstruction of lymphatic channels following the surgical removal of lymph nodes and fibrosis due to irradiation. This can be treated with manual lymphatic drainage. An increase of tumor recurrence due to this therapy is at controversial discussion. In a retrospective study 191 patients treated for head and neck cancer were questioned on occurrence of lymphedema and therapy with manual lymphatic drainage. 100 patients had received lymphatic drainage, whereas 91 patients belonged to the group without lymphatic drainage therapy. In 37 cases a tumor recurrence or local metastases were reported, 18 of whom had received lymphatic drainage and 19 belonged to the control group. Among these 37 patients neither the group with lymphatic drainage nor the control group differed significantly concerning stage of cancer, histopathological grading, the in sano/non in sano resection of the primary tumor and a lymphangiosis carcinomatosa. An increased recurrence rate among patients who underwent a lymphatic drainage therapy could not be found. A lymphatic drainage therapy for patients presenting with lymphedema after the oncological therapy does not increase the rate of local recurrencies. Moreover it improves the quality of life after the cancer therapy. As only few data are available for cases with non in sano surgery and tumors with lymphangiosis carcinomatosa these cases should be excluded from a lymphatic drainage therapy. A spreading of occult tumor cells in these patients might be possible.

Migration of the schistosomula of Schistosoma mansoni from skin to lungs.

SummaryThe number of schistosomula recovered from abdominal skin declined exponentially with time after infection. However, this decline was shown to be an untrue reflection of the numbers present because of changes in recoverability on days subsequent to infection. Digestion of skin by the enzymes collagenase and hyaluronidase produced a small increase in the number of schistosomula recovered. The number of schistosomula present in abdominal skin and capable of reaching maturity was estimated by exciting the area to which cercariae had been applied, from groups of hosts at daily intervals after exposure. The number of worms maturing in each group of hosts was then determined. The mean duration of stay of schistosomula in mouse, hamster and rat abdominal skin was estimated at 88, 64·5 and 70 h, respectively. The fluid content of abdominal skin to which cercariae had been applied, increased following infection but it was concluded that this alone was not the predominant factor controlling exit of worms. The stimulation of a delayed hypersensitivity response not directed against schistosomes (in mice previously sensitized with 1-chloro,2–4-dinitrobenzene (DNB)) 1 day after exposure to cercariae, produced a significant increase in the number of schistosomula leaving the skin and reaching maturity. Schistosomula can be recovered from the axial lymph nodes of mice, hamsters and rats. If the schistosomula from mice are injected into the tail vein of uninfected mouse hosts, they have the same chance of maturing as comparable skin schistosomula. They are therefore apparently unharmed by their passage through the nodes. Interference with lymphatic drainage by surgical removal of lymph nodes has no effect on the number of schistosomula recovered from the lungs, but the peak recovery is delayed by 24 h. The hamster cheek-pouch, a site with no afferent lymphatic drainage, was also used to investigate the importance of the lymphatic exit route. There was no reduction in the number of adult worms recovered following infection at this site compared with the normal abdominal skin site. The migration of schistosomula to deeper tissues and their entry into blood vessels was followed using the cheek-pouch preparation. It was concluded that the major route of exit from the skin is the blood vascular system.