Incidence Of Micrometastases Research Articles

V03-12 ROBOTIC-ASSISTED LAPAROSCOPIC RPLND FOR PARATESTICULAR RHABDOMYOSARCOMA USING 5 MM INSTRUMENTS IN PEDIATRIC SETTING

You have accessJournal of UrologyPediatrics (V03)1 Sep 2021V03-12 ROBOTIC-ASSISTED LAPAROSCOPIC RPLND FOR PARATESTICULAR RHABDOMYOSARCOMA USING 5 MM INSTRUMENTS IN PEDIATRIC SETTING Angeline Johny, Vinaya Bhatia, Alan Hsieh, Jeffrey White, and Chester Koh Angeline JohnyAngeline Johny More articles by this author , Vinaya BhatiaVinaya Bhatia More articles by this author , Alan HsiehAlan Hsieh More articles by this author , Jeffrey WhiteJeffrey White More articles by this author , and Chester KohChester Koh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001991.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The primary objective of this video is to demonstrate that the robotic approach using 5 mm instruments for primary retroperitoneal lymph dissection (RPLND) in the pediatric patient population with paratesticular rhabdomyosarcoma (PT-RMS) is an effective and safe procedure with favorable oncologic outcomes. Patients greater than 10 years of age with PT-RMS are often under staged and under treated. Additionally, the incidence of micrometastases has been shown to be as high 40%. Micrometastases is not amenable to chemotherapy and as such, the current US recommendation is for patients who are ten years and older with PT-RMS to undergo an ipsilateral retroperitoneal lymph node dissection regardless of radiographic findings. Following initiation of these guidelines, studies have demonstrated that ipsilateral RPLNDs have improved overall survival to 86%. METHODS: In this video, two case presentations were discussed demonstrating both left and right unilateral RPLND templates. For our left template, the patient is an 11 year old male with unremarkable history who presented with one month history of enlarging left hemiscrotum and work-up notable for elevated LDH of 577. He underwent a left radical inguinal orchiectomy with final pathology demonstrating a spindle cell RMS variant with positive margins. For our right template, the patient is a 10 year old male with history of Wiskott-Aldrich Syndrome with associated thrombocytopenia who also presented with a large painless right scrotal mass. Work-up was notable for LDH of 1012. He underwent a right radical inguinal orchiectomy with final pathology demonstrating Embryonal RMS with spermatic cord, tunic, and epididymal. Both patients underwent a primary robotic RPLND using 5 mm instruments and tolerated the procedure well, with favorable immediate post operative and long term oncologic outcomes. RESULTS: To approach our template adequately, we planned the following port placement: an 8 mm camera port at the superior margin of the umbilicus, two 5 mm robotic ports in the midline, with one inferior to the xiphoid, and the second inferior to the umbilicus but superior to the bladder. The assistant port was placed in the right versus left lower quadrant depending on the laterality of the RPLND. This port placement permits visualization of the renal hilar vessels, the great vessels, the sympathetic nerve trunks, as well as the ureter and major pelvic vessels, and was modified from techniques already described by Cost et al. 2012. CONCLUSIONS: Robotic assisted RPLND enables urologists to easily and safely to apply the benefit of minimally invasive surgery with 5 mm instruments. The major advantages of the robotic approach include reduced morbidity and mortality with preserved oncologic outcomes, enhanced visualization, and heightened instrument precision. Barriers to wide spread utilization of this technique include steep learning curve, need for proctor to oversee procedure, as well as cost. Nonetheless, our video demonstrates that the advantages of using 5 mm robotic instrument ports during a primary RPLND in the pediatric setting are technically feasible, with enhanced clinical and oncologic outcomes. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e225-e226 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angeline Johny More articles by this author Vinaya Bhatia More articles by this author Alan Hsieh More articles by this author Jeffrey White More articles by this author Chester Koh More articles by this author Expand All Advertisement Loading ...

Clinicopathological features and incidence of micrometastases in the bone marrow and peritoneum in advanced carcinoma of stomach in Indian patients

Background: Gastric cancer is associated with high mortality. The current five-year survival rate is less than 20%. Preventing the development of gastric cancer or finding it at the earliest possible stage is a far more cost-effective way of dealing with this tumour than the treatment of patients with advanced local regional or metastatic disease. The introduction of immunocytological methods that using monoclonal antibodies, sensitive enough to identify even single tumour cells can now be used to detect secondary metastatic sites. The objective of this study was to evaluate the patients with advanced gastric carcinoma using various factors such as presenting symptoms, predisposing risk factors and evidence of micro metastases by analysis of bone marrow and peritoneal cytology and also to identify any specific risk factors in a group of patients and if there were evidence of early micro metastases in these patients.Methods: Around 30 patients with histologically and endoscopically diagnosed gastric carcinoma, admitted in CMCH, surgery unit I was included in the study. All patients with gastric carcinoma had bone marrow smear and biopsy prior to surgery.Results: In all 30 patients, the periperal bone marrow smears and the bone marrow biopsy was negative for malignant cells. Only 1 patient had evidence of atypical cells on examination of the peritoneal fluid for cytology. 14 patients had less than 3 lymph nodes positive. In 7 patients, more than 3 lymph nodes were positive. 23.3% of the patients had H.Pylori associated gastritis.Conclusions: Smoking and alcohol were found to be significant risk factor. There was a significant association of H.pylori infection in the group. There was only one patient detected to have malignant cells in the peritoneal washings analyzed cytologically. In this study, no significant incidence of micro metastases in the bone marrow or elevated CEA levels in the peritoneal fluid were found.

Micrometastases in sentinel lymph node in endometrial cancer patients

Detection of micrometastases in sentinel lymph nodes (SLN) extends our knowledge of lymphatic spread in endometrial cancer, although its clinical significance has not yet been confirmed. The aim of study was to determine the incidence of SLN micrometastases and to analyze the association between micrometastases and disease relapse. Fifty-four patients with endometrioid endometrial cancer underwent routine surgical therapy and sentinel lymph node biopsy (SLNB). SLNB was performed using two techniques: cervical injection of 99mTc-labelled albumin or blue dye and fundal injection of blue dye. SLNs were subjected to ultrastaging with immunohistochemistry (AE1/AE3, 150µm). At least one SLN was detected in 51 patients (94.4%) and bilateral SLN detection was achieved in 80.4%. Nodal macrometastases were found in 3 patients (6.3%). SLNB enabled us to detect nodal macrometastases in 2 out of those 3 patients. In the third case, detection of SLN micrometastasis allowed to correctly determine the nodal status, thus avoiding the false negative result of SLNB. In 48 patients with detected 184 SLNs, there were 4 patients (8.3%) with micrometastases and 4 (8.3%) with ITC foci. No significant associations between the presence of risk factors (grade, myometrial invasion, cervical invasion, lymphovascular space invasion) and incidence of micrometastases and/or ITC foci in SLNs were found. Detection of micrometastases may result in lower false-negative rate, thus increasing SLNB safety.

Quantitative Analysis of Detected Sentinel Lymph Nodes and the Incidence of Micrometastases Using Two Different Methods of Surgical Melanoma Treatment-Pilot Study

The aim of our study was to compare the number of detected sentinel lymph nodes and the incidence of micrometastases between two groups of patients with cutaneous melanoma.Methods: 100 patients were divided in to two groups: group V and group D. Group V patients (50) with melanoma underwent a single-stage surgery-radical excision of the tumour with sentinel lymph node biopsy (study group “V”). Group D patients (50) with melanoma underwent two-stage surgery; initially primary diagnostic excision of the tumour (0.5 cm from margins of the lesion) followed by a radical re-excision of the post-operative scar and sentinel lymph node biopsy (study group “D“).Results: Study groups “V” and “D” were tested for homogeneity with regard to age, melanoma thickness, location of melanoma, type of melanoma, and ulceration. The groups were found to be homogenous. The average number of removed sentinel lymph nodes in group “D” was 1.0 more than in group “V” (p < 0.05). The averages were 3.7 and 2.7 respectively with a SD of 1.8. The relationship between the SL node staining and type of surgery was (p < 0.05). 49.6% stained radioactive sentinel lymphnodes at the time of surgery was found in group “V”, while 33.9% in group “D”. Conclusions: Using two different early-stage cutaneous melanoma management techniques significantly more sentinel lymph nodes (p = 0.006) were detected using the two-stage surgery approach. However, there was no significant difference between the two approaches regarding the number of sentinel lymph nodes with micrometastases that were detected and excised.

Distribution of brain metastases: implications for non-uniform dose prescriptions

The aim of this study was to determine the disease-specific distribution of brain metastases and, using radiobiological modelling, estimate how these anatomical tendencies might be exploited when delivering prophylactic whole-brain radiotherapy for small cell lung cancer in complete remission. Disease-specific brain metastasis atlases were created by mapping brain metastases to a standard image set from a database of patients who were to receive external beam radiation therapy. The specific diseases investigated included lung (both small cell and non-small cell), breast, renal and gynaecological cancers as well as melanoma. Radiobiological modelling was used to estimate how much improvement, in terms of the metastasis-free rate at 3 years, might be possible with non-uniform dose distributions if there are spatial biases in the incidence of micrometastases from small cell lung cancer. For lung and breast cancer, there was an increased probability of cerebellar metastases compared with what would be predicted based solely on brain volume. This trend was not evident for renal cancer, gynaecological malignancies or melanoma. Radiobiological models suggest that if there is a non-uniform distribution of microscopic brain metastases in patients with small cell lung cancer, higher population-based metastasis-free rates might be achievable with non-uniform irradiation compared with the same integral whole-brain dose delivered as a uniform prescription.

Incidence of micrometastases in histologically negative para-aortic lymph nodes in advanced cervical cancer patients

Objective Aims of the study were to identify the incidence of micrometastases in negative para-aortic lymph nodes, and to assess the utility of ultrastaging in histologic evaluation of para-aortic lymph nodes. Material and methods Patients with advanced cervical cancer and negative para-aortic lymph nodes after routine histology examination were included. Paraffin-embedded tissue blocks were cut into 5-μm-thick slides at step serial sections at 200-μm intervals until there was no lymph node tissue left. 7 to 14 slides were obtained per lymph node and an immunohistochemistry staining with anti-cytokeratin antibody (EA1/EA3) was performed. Results 581 histologically negative aortic nodes of 24 patients with advanced cervical cancer were assessed for para-aortic micrometastases (PAM). The incidence of micrometastases by the total number of studied lymph nodes was 0.003%. PAM were identified in 2 patients (8.3%), and additional submicrometastases were also found in one of them (4.1%). A single metastatic cluster of less than 0.2 mm was found in an afferent lymphatic vessel of another patient, not considered as a submicrometastases. PAM incidence was too low to allow for evaluation of associated risk factors, and for analysis of prognostic significance. Conclusion Although examination of PAM with ultrastaging and IHC is expensive and time-consuming, and difficult to be routinely applied to all negative lymph nodes retrieved in a para-aortic lymphadenectomy, this study adds to current evidence that removal of aortic nodes may benefit a subgroup of advanced cervical cancer patients with PAM and negative aortic lymph node at imaging techniques including PET-scan.

Authors’ response to Shah’s letter concerning the editorial “The future of the TNM staging system in laryngeal cancer: time for a debate?”

Sir, We thank Dr. Shah for his letter [1] regarding the editorial entitled “The future of the TNM staging system in laryngeal cancer: time for a debate?” We think that it would be both practical and useful to explore the possibility of inclusion in the UICC/AJCC staging system, a designation of both (1) the presence or absence of micrometastases, as well as (2) the presence of isolated tumor cells found in general circulation (blood, bone marrow, other distant sites). Cases with only micrometastases might, in such scheme, be identiWed by the addition of “(mi)” to the pN and/or pM category [e.g., pN1 (mi) or pM1 (mi)] [2]. Admittedly, one wishing to utilize such an “ultrastaging” system would be well advised to formally identify the precise pathologic methods of evaluation used to arrive at such a classiWcation. It is virtually certain that detection modes more sensitive than conventional light microscopic pathologic methods (as for example, immunocytochemistry and molecular biology) will be required to identify the otherwise elusive micrometastases and isolated neoplastic cells whose identiWcation is part of such a scheme of ultrastaging [3]. Ultrastaging techniques are today more expensive than the traditional hematoxylin and eosin staining, but they clearly will increase the chances of detection of micrometastases; as such, such techniques are continuously expanding in their availability, playing (in the minds of many investigators) an increasingly important role in clinical practice [3–5]. However, the mere fact that it may be possible to carry out ultrastaging of head and neck cancer patients, does not automatically mean that such an elaborate staging will beneWt them. It is possible that detection of micrometastases within the lymph node which are overlooked when nodes are analyzed by conventional pathologic methods may be of great importance in determining the prognosis [6]. However, it appears as though not all isolated tumor cells which may be found in the lymph nodes or in general circulation (blood, bone marrow, other distant sites) are clinically signiWcant. Only a very small percentage of circulating tumor cells (0.05%) seem to be capable of surviving and establishing a metastatic focus [7]. As is the case in routine pathologic analysis, the clinical metastatic work-up also regularly overlooks (or, in other words, underestimates) the incidence of micrometastases. As well, it is now known that isolated tumor cells may be detected in the bone marrow of patients who bear no clinically identiWable distant metastases; too, such isolated tumor cells may sometimes be found in regional lymph nodes in which no metastases have been found by conventional stains. In one series, individual disseminated carcinoma cells were detected in bone marrow aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and neck region. This contamination of the bone marrow by individual metastatic carcinoma cells was demonstrated by the use of immunocytochemistry, relying on a monoclonal antibody raised against cytokeratin no. 19. In the clinical stage I patients, tumor cells were detected only in 23.3% of the patients, whereas in stage IV patients almost twice as many individuals (47.7%) presented with tumor cells in the bone marrow. Patients who were shown to possess these A. Ferlito (&) · A. Rinaldo Department of Surgical Sciences, ENT Clinic, University of Udine, Policlinico Universitario, Piazzale S. Maria della Misericordia, 33100 Udine, Italy e-mail: a.ferlito@uniud.it

A standardized sentinel lymph node enhanced pathology protocol (SEPP) in patients with breast cancer

Sentinel lymph node (SLN) biopsy allows enhanced pathology with serial sections and immunohistochemical analysis of the retrieved node. We present our experience with a simple, practical, pathology protocol. We analysed 416 consecutive breast cancer patient who underwent SLN biopsy. These were studied with six couples of sections at three different levels, each stained with hematoxylin-eosin (H/E) and immunohistochemistry (IHC) (MNF 116). With conventional analysis the SLN was positive in 106/416 cases (25%). The addition of serial sections, according to the protocol, allowed diagnoses of micrometastases (MICRO) (n = 22) or isolated tumor cells (ITC) (n = 38) or MICRO (n = 1) in 51/416 patients (14.6%). Specifically, the diagnosis was undertaken at level I (8.9%), level II (4%), or level III (1,6%). The incidence of MICRO or ITC was not different in T1 and T2 cases (13% vs. 15%, P = 0.7). The addition of the third level of analysis added very little both in T1 and T2 cancers (1.3% vs. 3.8%, P = 0.1). Serial sectioning of the SLN allows diagnosis of MICRO and ITC in a significant percentage of cases. Adoption of our protocol seems practical, as the incidence of level III positivity is extremely low, particularly in T1 cancers, and additional sections would be, therefore, unlikely useful.

Prevalence of bone marrow micrometastases in esophagogastric cancer patients with and without neoadjuvant chemoradiotherapy

Background Bone marrow micrometastases are present in a high proportion of patients undergoing curative resection for esophagogastric cancer. The incorporation of preoperative systemic therapies into these patients’ treatment is widely practiced. This study investigates the effect of neoadjuvant chemoradiotherapy (CRT) on the incidence of micrometastases and the viability of detected tumor cells. Materials and methods Rib bone marrow was obtained from patients ( n = 106) in three centers, who were selected for potentially curative resection. Patients received neoadjuvant CRT plus surgery ( n = 55), or surgery alone ( n = 51). To detect micrometastases, mononuclear cells were isolated from fresh marrow and immediately stained immunohistochemically with an anti-cytokeratin-18 antibody using the APAAP technique. Tumor cell viability was assessed by immunohistochemical staining of marrow cell cultures for cytokeratin-positive cells. Results Micrometastases were detected in fresh marrow in 42% (23/55) of patients who received neoadjuvant CRT plus surgery, and in 67% (34/51) of patients treated with surgery alone. Viable tumor cells were demonstrated in 10 of 18 marrow cultures from CRT plus surgery cases. In this patient subset, combination of results of staining fresh and cultured marrow significantly increased micromet detection to 78%. Conclusions A significant proportion of patients with esophagogastric cancer have disseminated viable tumor cells at time of surgery, irrespective of pre-operative treatment. The use of marrow culture in parallel with fresh marrow staining may increase the detection of micrometastases. The persistence of tumor cells resistant to systemic therapy may explain why these regimens fail in a majority of patients.

Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma.

Lymph node status is a major determinant of disease recurrence after patients undergo curative resection for gastric carcinoma. A proportion of patients without lymph node metastasis develop systemic recurrences. Recent studies in a range of solid tumors have found a high incidence of micrometastases in the regional lymph nodes of patients with apparently negative lymph nodes. In patients with breast and colorectal carcinoma, the presence of micrometastases has been associated with a poorer prognosis. In patients with gastric carcinoma, the significance of micrometastases in lymph nodes remains controversial. Most published reports on this subject suffer from the problems of small sample size and selection bias. One hundred seven patients with pathologic T2N0M0 (tumor invades muscularis propria or subserosa [T2], no regional lymph node metastasis [N0], and no distant metastasis [M0]; pT2N0M0) gastric carcinoma who underwent gastric resection between 1984 and 1990 at the National Cancer Center Hospital were studied. Two consecutive sections were newly prepared from each lymph node for hematoxylin and eosin staining and immunohistochemical staining (IHC) with antibody against cytokeratin. Associations between clinicopathologic factors and the presence of micrometastases as well as micrometastases and survival were sought. Micrometastases were identified in 38 of 107 patients (35.5%) and in 87 of 4484 lymph nodes (1.94%) by IHC. The incidence of micrometastases was significantly higher in patients with infiltrative tumors than in patients with expansive, growing tumors (P = 0.02). Other clinicopathologic findings had no statistically significant correlation with the incidence of micrometastases. The 5-year survival rates of patients with and without micrometastases were 94% and 89%, respectively. Similarly, the 10-year survival rates were 79% and 74%, respectively. The survival curves of patients with or without micrometastasis were nearly superimposed (P = 0.86). The presence of immunohistochemically detected micrometastases in the regional lymph nodes did not affect the survival of Japanese patients with pT2N0M0 gastric carcinoma who had undergone gastrectomy with D2 lymph node dissection.

Lymph node microinvolvement in adenocarcinoma of the gastro-esophageal junction

Introduction: In the past decade there has been a alarming rise in the incedence of adenocarcinoma of the gastro-esophageal junction in western countries. There at present time still much discrepancies in the classification of tumors of the gastro-esophageal junction.We investigated possible differences and the prognostic impact of lymph node microinvolvement and micrometastases in adenocarcinoma of the gastro-esophageal junction . Material and methods: We examined in 3987 lymph nodes of 145 ROresected adenocarcinoma of the gastro-esophageal junction with irnmunhistochemical techniques (antibody cocktail AEl/AE3 and antibody BerEP4) the incidence of micrometastases and microinvolvement. Micrometastases were defined as single tumor cells or cellclusters smaller than 0.2mm in diameter with stromal reaction, classified as microinvolvement when the stromal reaction was missed. Results: In 90 (2.3%) of the lymph nodes microinvolvement and in 106 (2.7%) micrometastases were detectable.Of the 145 investigated patients, 75 were classified as pNO and 70 patients had lymph node metastases in standard histological examination. In contrast to the pNOpatients showed the pN+ patients significant more micrometastases (17.3% vs. 60%); p<0.05). The presence of lymph node micrometastases correlated with the pT-stade and the non-intestinal classification according to Lauren. Patients with true cardia carcinoma and subcardial carcinoma showed a significant higher rate of micrometastases than adenocarcinoma of the distal esophagus (24.4% vs. 6.7%; p<0.05). The survival analysis showed a significant difference between pNO staged patients with micrometastases compared to patients without micrometastases. The microinvolvement was without impact on survival. Conclusion: In contrast to adenocarcinoma of the distal esophagus, patients with true cardia carcinoma and subcardial carcinoma had a higher incidence of micrometastases. This request a more specialized classification of adenocarcinoma of the gastro-esophageal j unction and supports the different surgical extension and lymphadenectomy in this tumor entities.

Caution concerning micrometastatic breast carcinoma in sentinel lymph nodes

A pilot study by Dowlatshahi et al. observed a high (58%) incidence of micrometastases in the sentinel lymph nodes (SLNs) of patients with small primary breast carcinomas when immunohistochemical preparations of serial sections of the lymph nodes were examined. The prognostic implications of these findings are unknown and, until they are, evaluating SLNs in this manner should be avoided in routine clinical practice. See also pages 990–6.

Micrometastases from squamous cell carcinoma in neck dissection specimens

The incidence of micrometastases in cervical lymph nodes from squamous cell carcinomas of the head and neck was studied using routine histopathological examination. Micrometastases were found in 66 lymph nodes in 41 of the 92 tumor-positive neck dissection specimens. The detection of these micrometastases influenced postoperative treatment in 3 of the 77 patients with neck node metastases. The value of additional sectioning for detecting micrometastases was thus assessed. Sectioning at a deeper level in 600 originally histopathologically negative lymph nodes from 64 patients revealed 7 additional micrometastases in 5 patients. Antikeratin staining with a mixture of two monoclonal antibodies (AE1 and AE3) revealed 4 micrometastases in 739 originally histopathologically negative lymph nodes in 3 of 13 patients studied. Because of the unknown prognostic significance of micrometastases and the consequent arbitrary consequences for postoperative treatment, present findings show that the extra workload of immunostaining and deeper sectioning does not warrant their routine use in clinical practise.

Divergency between incidence of microscopic and macroscopic metastases.

In a rat fibrosarcoma model (D-12), the incidence of macroscopic metastases was generally low but critically dependent on the site of the primary tumor implant; surgical removal of the primary tumor either induced or markedly enhanced the outgrowth of macroscopic metastases (Keller 1981). The present histological and biological findings indicate that dissemination of neoplastic cells and colonization of draining lymph nodes is a spontaneous, early occurring and continuing process. The incidence of micrometastases within lymph nodes by far exceeded the incidence of macroscopically evident metastases. Other evidence suggests that the growth characteristics of D-12 tumor cells derived from metastases are not measurably different from D-12 cells inducing primary tumor growth.