Janus Emulsion Biosensors for Anti-SARS-CoV-2 Spike Antibody.

The spread of the COVID-19 pandemic around the world has revealed that it is urgently important to develop rapid and inexpensive assays for antibodies in general and anti-SARS-CoV-2 IgG antibody (anti-SARS-CoV-2 spike glycoprotein S1 antibody) in particular. Herein we report a method to detect the anti-SARS-CoV-2 spike antibody level by using Janus emulsions or Janus particles as biosensors. Janus emulsions are composed of two immiscible hydrocarbon and fluorocarbon oils. The hydrocarbon/water interfaces are functionalized with a secondary antibody of IgG protein and SARS-CoV-2 spike receptor binding domain (RBD), to produce two different Janus emulsions. Mixtures of these Janus droplets enable the detection of the anti-SARS-CoV-2 spike IgG antibody in an agglutination assay caused by the antibody's binding to both the secondary antibody of IgG antibody and SARS-CoV-2 spike protein RBD. Both qualitative optical images and quantitative fluorescence spectra are able to detect the level of anti-SARS-CoV-2 spike antibody at concentrations as low as 0.2 µg/mL in 2 h. The detection results of clinical human serum samples using this agglutination assay confirm that this method is applicable to clinical samples with good sensitivity and specificity. The reported method is generalizable and can be used to detect other analytes by attaching different biomolecular recognition elements to the surface of the Janus droplets.

Electric-Field-Induced Chirality in Columnar Liquid Crystals.

We describe a novel class of tetraphenylbenzene-based discotic molecules with exceptional self-assembling properties. Absorption and fluorescence studies confirmed the formation of J-type aggregates in solution. The discotic mesogens also show an enhancement of the emission upon aggregation. Interestingly, these discotic molecules displayed enantiotropic hexagonal columnar liquid crystal (LC) phases that can be switched into a helical columnar organization by application of an electric field. The helical columns arise from the electric-field-induced tilt of the polar fluorobenzene ring that directs all of the peripheral phenyl groups into a propeller-like conformation with respect to the central benzene core. A cooperative assembly process of these propeller-shaped molecules resolves into a helical columnar organization, in which the preferred helical sense is obtained from the stereogenic center proximate to the polar carbon-fluorine bond. The ease of inducing chirality in columnar LCs by an electric field presents opportunities to create next-generation chiral materials for a variety of applications.

Reconfigurable Pickering Emulsions with Functionalized Carbon Nanotubes.

Pickering emulsions (PEs) achieve interfacial stabilization by colloidal particle surfactants and are commonly used in food, cosmetics, and pharmaceuticals. Carbon nanotubes (CNTs) have recently been used as stabilizing materials to create dynamic single emulsions. In this study, we used the formation of Meisenheimer complexes on functionalized CNTs to fabricate complex biphasic emulsions containing hydrocarbons (HCs) and fluorocarbons (FCs). The reversible nature of Meisenheimer complex formation allows for further functionalization at the droplet-water interface. The strong affinity of fluorofluorescent perylene bisimide (F-PBI) to the CNTs was used to enhance the assembly of CNTs on the FC-water interface. The combination of different concentrations of the functionalized CNTs and the pelene additive enables predictable complex emulsion morphologies. Reversible morphology reconfiguration was explored with the addition of molecular surfactants. Our results show that the interfacial properties of functionalized CNTs have considerable utility in the fabrication of complex dynamic emulsions.

Pentiptycene Polymer/Single-Walled Carbon Nanotube Complexes: Applications in Benzene, Toluene, and o-Xylene Detection.

We report the dispersion of single-walled carbon nanotubes (SWCNTs) using pentiptycene polymers and their use in chemiresistance-based and QCM-D sensors. Poly(p-phenylene ethynylene)s (PPEs) incorporating pentiptycene moieties present a concave surface that promotes π-π interactions and van der Waals interactions with SWCNTs. In contrast to more common polymer-dispersing mechanisms that involve the wrapping of polymers around the SWCNTs, we conclude that the H-shape of pentiptycene groups and the linear rigid-rod structure creates a slot for nanotube binding. UV-vis-NIR, Raman, and fluorescence spectra and TEM images of polymer/SWCNTs support this dispersion model, which shows size selectivity to SWCNTs with diameters of 0.8-0.9 nm. Steric bulk on the channels is problematic, and tert-butylated pentiptycenes do not form stable dispersions with SWCNTs. This result, along with the diameter preference, supports the model in which the SWCNTs are bound to the concave clefts of the pentiptycenes. The binding model suggests that the polymer/SWCNTs complex creates galleries, and we have demonstrated the binding of benzene, toluene, and o-xylene (BTX) vapors as the basis for a robust, sensitive, and selective sensing platform for BTX detection. The utility of our sensors is demonstrated by the detection of benzene at the OSHA short-term exposure limit of 5 ppm in air.

Fluorescent Janus emulsions for biosensing of Listeria monocytogenes.

Here we report a sensing method for Listeria monocytogenes based on the agglutination of all-liquid Janus emulsions. This two-dye assay enables the rapid detection of trace Listeria in less than 2 h via an emissive signal produced in response to Listeria binding. The biorecognition interface between the Janus emulsions is assembled by attaching antibodies to a functional surfactant polymer with a tetrazine/transcyclooctene click reaction. The strong binding between Listeria and the Listeria antibody located at the hydrocarbon surface of the emulsions results in the tilting of the Janus structure from its equilibrium position to produce emission that would ordinarily be obscured by a blocking dye. This method provides rapid and inexpensive Listeria detection with high sensitivity (<100 CFU/mL in 2 h) that can be paired with many antibody or related recognition elements to create a new class of biosensors.

Dynamically Reconfigurable, Multifunctional Emulsions with Controllable Structure and Movement.

Dynamically reconfigurable oil-in-water (o/w) Pickering emulsions are developed, wherein the assembly of particles (i.e., platinum-on-carbon and iron-on-carbon particles) can be actively controlled by adjusting interfacial tensions. A balanced adsorption of particles and surfactants at the o/w interface allows for the creation of inhomogeneity of the particle distribution on the emulsion surface. Complex Pickering emulsions with highly controllable and reconfigurable morphologies are produced in a single step by exploiting the temperature-sensitive miscibility of hydrocarbon and fluorocarbon liquids. Dynamic adsorption/desorption of (polymer) surfactants afford both shape and configuration transitions of multiple Pickering emulsions and encapsulated core/shell structured can be transformed into a Janus configuration. Finally, to demonstrate the intrinsic catalytic or magnetic properties of the particles provided by carbon bound Pt and Fe nanoparticles, two different systems are investigated. Specifically, the creation of a bimetallic microcapsule with controlled payload release and precise modulation of translational and rotational motions of magnetic emulsions are demonstrated, suggesting potential applications for sensing and smart payload delivery.

Rapid Detection of Salmonella enterica via Directional Emission from Carbohydrate-Functionalized Dynamic Double Emulsions.

Reliable early-stage detection of foodborne pathogens is a global public health challenge that requires new and improved sensing strategies. Here, we demonstrate that dynamically reconfigurable fluorescent double emulsions can function as highly responsive optical sensors for the rapid detection of carbohydrates fructose, glucose, mannose, and mannan, which are involved in many biological and pathogenic phenomena. The proposed detection strategy relies on reversible reactions between boronic acid surfactants and carbohydrates at the hydrocarbon/water interface leading to a dynamic reconfiguration of the droplet morphology, which alters the angular distribution of the droplet's fluorescent light emission. We exploit this unique chemical-morphological-optical coupling to detect Salmonella enterica, a type of bacteria with a well-known binding affinity for mannose. We further demonstrate an oriented immobilization of antibodies at the droplet interface to permit higher selectivity. Our demonstrations yield a new, inexpensive, robust, and generalizable sensing strategy that can help to facilitate the early detection of foodborne pathogens.

Emulsion Agglutination Assay for the Detection of Protein-Protein Interactions: An Optical Sensor for Zika Virus.

A new class of Janus emulsion agglutination assay is reported for the detection of interfacial protein-protein interactions. Janus emulsion droplets are functionalized with a thermally stable, antigen binding protein rcSso7d variant (rcSso7d-ZNS1) for the detection of Zika NS1 protein. The emulsion droplets containing fluorescent dyes in their hydrocarbon and fluorocarbon phases intensify the intrinsic optical signal with the emission intensity ratio, which can be detected by a simple optical fiber. This assay provides an opportunity for the in-field detection of Zika virus and other pathogens with a stable, inexpensive, and convenient device.

Current Status of Uterine Leiomyosarcoma in the Tohoku Region: Results of the Tohoku Translational Center Development Network Survey.

BACKGROUND: To prepare for a future clinical trial for improving the long-term prognosis of patients with uterine leiomyosarcoma (ULMS), we conducted a multi-institutional survey in the Tohoku region of Japan. METHODS: We conducted a retrospective cohort study between 2011 and 2014 in member institutions of the Tohoku Translational Research Center Development Network. RESULTS: A total of 53 patients with ULMS were registered in 31 institutions for the present survey. The median patient age was 56 years, 67.9% of the patients were postmenopausal, 88.7% had a performance status of 0 or 1, and only 6 patients (11.3%) showed preoperative evidence of malignancy. Although retroperitoneal lymphadenectomy was performed in only 26.4% of patients, 64.2% patients were identified as having FIGO stage 1 disease; 73.6% were eligible to undergo complete surgery. Among 36 patients who were treated with postoperative chemotherapy, 28 (77.8%) received docetaxel and gemcitabine combination therapy. The most frequent recurrence site was the lungs, and the median progression-free survival of all enrolled patients was 11.7 months. However, the median progression-free survival and the median overall survival in patients with stages III and IV disease were 3.4 and 11.4 months, respectively. CONCLUSION: Although ULMS was associated with a high rate of complete or optimal surgery, the long-term prognosis was poor. Effective postoperative therapy should be developed to improve the long-term prognosis of patients with ULMS.

Leptomeningeal metastasis from gynecologic cancers diagnosed by brain MRI.

Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian cancers, one tubal cancer, one peritoneal cancer, two endometrial cancers, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high-priority inspection for the diagnosis of this devastating complication.

Cytokeratin 7-positive/cytokeratin 20-negative cecal adenocarcinoma metastatic to the uterine cervix: a case report.

BACKGROUND: The vast majority of uterine cervical malignancies are primary carcinomas, and secondary neoplasms that metastasize to the uterine cervix from a distant organ are uncommon. Although relatively rare, metastases to the uterine cervix from a primary colon cancer have been reported. We report a rare case of metastatic carcinoma originating from a cecal adenocarcinoma with an unusual cytokeratin 7/cytokeratin 20 immunophenotype. CASE PRESENTATION: A 74-year-old postmenopausal Japanese woman was referred to our hospital for the evaluation of a uterine tumor. She had a past medical history of cecal cancer and had undergone laparoscopically assisted right hemicolectomy at the age of 69 years. During follow-up, she was found to have elevated levels of the tumor markers carbohydrate antigen 19-9 (179.7 IU/mL) and carcinoembryonic antigen (26.9 µg/L). Positron emission tomography/computed tomography showed a focus of high 18F-fluorodeoxyglucose uptake in her uterus. Examination of a cervical biopsy found a poorly differentiated adenocarcinoma that was immunopositive for cytokeratin (CK)7 and caudal-related homeobox 2 (CDX2) expression and immunonegative for cytokeratin 20 expression. The patient underwent radical hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination found invasive growth of irregular and atypical ductal hyperplasia. Immunohistochemical staining of the tumor specimen revealed the same immunophenotype as the biopsy specimen. The cecal cancer specimen from her previous surgery was also examined and found to have the same immunophenotype. The histopathological diagnosis was cecal adenocarcinoma metastatic to the uterine cervix. The patient is currently receiving adjuvant chemotherapy and to date is without evidence of recurrent disease. CONCLUSIONS: Our report illustrates the importance of immunohistochemistry for the correct diagnosis of the origin of a uterine cervical adenocarcinoma in a patient with a medical history of colorectal cancer. Re-examination of a previous oncological specimen is critical for cases with a uterine lesion that is difficult to identify as primary or metastatic cancer.

Isolated torsion of the fallopian tube in a menopausal woman and a pre-pubertal girl: two case reports.

INTRODUCTION: Isolated torsion of the fallopian tube without an ovarian abnormality is an uncommon event, with an incidence of approximately 1 in 1,500,000 females. Isolated torsion of the fallopian tube occurs mostly in reproductive-aged women, and is thus extremely rare in menopausal women and pre-pubertal girls. CASE PRESENTATIONS: In case 1, 63-year-old Japanese woman presented with a 2-day history of acute lower abdominal pain. Menopause occurred at 53 years of age. Pelvic ultrasonography showed an enlarged mass (73 × 47 mm) on the right side of her uterus. An urgent laparoscopy was performed based on a presumptive diagnosis of right ovarian tumor torsion. During the laparoscopy, we noted a black, necrotic, solid tumor arising from the distal end of her right fimbria. Her right fallopian tube was twisted with the tumor, but her right ovary was normal and not involved. A laparoscopic tumorectomy with a right salpingectomy was performed. Her post-operative course was uneventful. In case 2, a 10-year-old Japanese girl presented with a 1-day history of lower abdominal pain associated with nausea and vomiting. Menarche had occurred 2 months earlier. A computed tomography and magnetic resonance imaging examination demonstrated a dilated tubal cystic mass with a normal uterus and bilateral ovaries. An urgent laparoscopy was performed based on a presumptive diagnosis of right fallopian tube torsion. During laparoscopy, her right fallopian tube was noted to be dark red, dilated, and twisted several times. Her right fimbria was necrotic-appearing and could not be preserved. Therefore, a laparoscopic right salpingectomy was performed. A histologic examination revealed ischemic changes with congestion of her right fallopian tube, which was consistent with tubal torsion. She had an uncomplicated post-operative course. CONCLUSION: We have presented two very rare cases of isolated fallopian tubal torsion. Radiologic interventions, such as computed tomography and magnetic resonance imaging, in addition to ultrasonography, are helpful diagnostic tools. Isolated torsion of the fallopian tube should be considered in the differential diagnosis of lower abdominal pain with a cystic mass and a normal ipsilateral ovary in all female patients, regardless of age.

Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

INTRODUCTION: Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. CASE PRESENTATION: A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. CONCLUSION: We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

Spontaneous retroperitoneal hemorrhage caused by rupture of an ovarian artery aneurysm: a case report and review of the literature.

INTRODUCTION: Spontaneous rupture of an ovarian artery aneurysm is extremely rare. Although a majority of these cases have been associated with pregnancy, there have been recent reports and reviews of rare cases that were not directly associated with pregnancy. Transcatheter arterial embolization is considered to be an alternative therapy to surgery. CASE PRESENTATION: A 44-year-old Japanese woman, gravida 3 para 3, presented to our emergency room complaining of intermittent right flank pain. She had undergone a cesarean section 2 years previously, and had no history of abdominal trauma. On admission, her blood pressure was 115/78 mmHg, pulse 70 beats per minute, and hemoglobin concentration 9.8 g/dL. Abdominal ultrasonography and contrast-enhanced dynamic computed tomography revealed a large retroperitoneal hematoma. Findings on three-dimensional computed tomography angiography suggested ruptured aneurysm of her right ovarian artery. A selective right ovarian artery angiogram revealed a tortuous aneurysm. Transcatheter arterial embolization using N-butyl-2-cyanoacrylate was performed. The aneurysm was successfully embolized, and her course after embolization was uneventful. She has remained symptom-free during 3 months of follow-up. CONCLUSIONS: This was a very rare case of a patient who had a retroperitoneal hemorrhage originating from an ovarian artery aneurysm. A review of published case reports found that contrast-enhanced computed tomography with reconstruction images is an excellent imaging tool. Diagnostic angiography and subsequent transcatheter arterial embolization are thought to be very effective for this condition.

Small cell carcinoma of the uterine cervix: clinical outcome of concurrent chemoradiotherapy with a multidrug regimen.

Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

Prospective study of sentinel lymph node biopsy without further pelvic lymphadenectomy in patients with sentinel lymph node-negative cervical cancer.

OBJECTIVE: The aim of the present study was to evaluate the incidence of lymphedema and cancer recurrence rate in patients with cervical cancer who undergo sentinel lymph node (SLN) biopsy alone in the absence of SLN metastases. PATIENTS AND METHODS: The study included 35 consecutive patients with cervical cancer scheduled for radical hysterectomy at Tohoku University Hospital between May 2006 and July 2009. All patients had International Federation of Gynecology and Obstetrics stages IA1 to IIA1 disease. Patients in whom SLNs were detected unilaterally or not detected and/or whose lymph nodes were diagnosed intraoperatively as positive metastasis underwent systemic pelvic lymphadenectomy. Patients who were found negative for SLN metastasis did not undergo further pelvic lymphadenectomy. RESULTS: The mean number of detected SLNs was 4.1 (range, 1-11). True lymph node metastasis could be detected in 11 (31%) of the 35 cases. Intraoperative frozen section identified correctly in 8 of 11 metastatic patients. Twenty-three patients underwent SLN biopsy alone without systematic pelvic lymphadenectomy. None of the 23 patients diagnosed with negative SLNs have experienced a lymph node recurrence in the pelvic cavity. New symptomatic lower extremity lymphedema was identified in 2 (8.7%) of the 23 patients who underwent SLN biopsy alone and in 5 (42%) of 12 patients who underwent systematic lymphadenectomy. CONCLUSION: Radical hysterectomy with SLN biopsy alone seems to be a safe and effective strategy for detection of lymph node metastasis and for reducing the number of patients with lower extremity lymphedema, but a more convenient and sensitive procedure for intraoperative diagnosis needs to be established.

Malignant transformation arising from mature cystic teratoma of the ovary: a retrospective study of 20 cases.

OBJECTIVES: Mature cystic teratoma (MCT) of the ovary rarely undergoes malignant transformation (MT). Malignant transformation carries a significantly worse prognosis than epithelial ovarian cancer, regardless of whether postoperative chemotherapy or radiotherapy is applied. The rarity of this tumor has posed a significant challenge to developing standardized postoperative management protocols. The aim of this study was to review our experience with MT and to describe our current treatment practices. METHODS: A retrospective chart review of these patients was performed that identified 20 women treated for MT of MCT at our centers between 1988 and 2008. RESULTS: The median age was 52.5 (range, 29-77) years. Fifteen patients had squamous cell carcinoma (SCC), and 5 patients had other histological subtypes. The International Federation of Gynecology and Obstetrics stage distribution was as follows: 11 were stage I, 4 were stage II, 4 were stage III, and 1 was stage IV. All patients underwent an initial laparotomy. Eleven patients received adjuvant treatment: 8 were treated with chemotherapy, 2 with concurrent chemoradiation therapy, and 1 with radiation therapy. Platinum-based chemotherapy was the first-line regimen. The overall 1-year survival rate was 70%. Significant correlations between overall survival and age, stage, and residual tumor were presented (P = 0.044, P = 0.0107, P < 0.0001, respectively). Eight patients with advanced stage died of their disease. Four patients, however, were treated with adjuvant chemotherapy or concurrent chemoradiation therapy and survived more than 1 year. One stage III patient had a disease-free interval of 2 years. Two cases of SCC treated with combination platinum/taxane chemotherapy temporarily responded. In the other 2 cases of SCC, concurrent chemoradiation therapy with nedaplatin also resulted in tumor regression. CONCLUSIONS: The prognosis of MT is highly dependent on age, stage, and optimal cytoreduction. Adjuvant treatment has not been standardized, although our experience supports the use of combination platinum/taxane chemotherapy.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

Detection of micrometastases in cervical cancer with a system that evaluates both sentinel and nonsentinel lymph nodes.

The aim is to reevaluate the accuracy of our sentinel lymph node (SLN) detection procedure and the use of SLN examination for detecting cervical cancer micrometastases. Patients affected by cervical cancer who underwent radical hysterectomy and total pelvic lymphadenectomy at Tohoku University Hospital from 2001 to 2003 were enrolled in this study. Patients in whom lymph node metastases were detected by routine histological examination or in whom no SLNs could be detected were excluded. Paraffin-embedded tissue blocks were cut into 3-microm thick slides at 200-microm intervals for both SLNs and non-SLNs. All lymph nodes were evaluated with step-serial sectioning and immunohistochemistry with an anticytokeratin antibody. One of the 10 patients had micrometastases, and 1 patient had isolated tumor cells (ITCs) in their SLNs. Thus, 2 (6%) of the 31 SLNs detected by our method had cancer cells. In contrast, none of the 309 non-SLNs obtained from 10 patients had micrometastases. The SLN micrometastases were detected in the right external iliac basin. The ITCs were detected in the left external iliac basin. The patient with micrometastases did not have vascular invasion but experienced recurrence. The case with ITCs had vascular invasion; however, she received adjuvant chemoradiotherapy and had no recurrence after 4 years. Our study suggests that only SLNs will contain micrometastases or ITCs, and non-SLNs will not. The SLNs detected by our method are probably real given the large total number of nodes evaluated. How micrometastases affect prognosis and the best way to detect them are areas of further study.

Detection of micrometastases in the sentinel lymph nodes of patients with endometrial cancer.

OBJECTIVE: We investigated the utility of sentinel lymph node (SLN) mapping for the detection of endometrial carcinoma micrometastases. We reevaluated the accuracy of our SLN detection procedure, this time combining step-serial section with cytokeratin immunostaining. PATIENTS AND METHODS: Between March 2002 and March 2005, consecutive patients undergoing laparotomy (total abdominal hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of renal veins) with SLN biopsy for endometrial cancer at Tohoku University Hospital were enrolled in this study. Excluded were patients in whom lymph node metastases were detected by routine histological examination or those without detectable SLNs. All surgically removed lymph nodes, including SLNs, were examined histopathologically by immunohistochemistry staining with an anti-cytokeratin antibody (AE1/AE3) combined with step-serial sectioning at 200-500 microm intervals. RESULTS: Four of seventy-four SLNs (5%) obtained from 20 patients had micrometastases or isolated tumor cells (ITC). In contrast, only 4 of the 1350 non-SLNs obtained from 20 patients (0.3%) had detectable micrometastases. The micrometastases were detected in the external iliac basin (two cases) and in the para-aortic area (two cases). The isolated tumor cell was detected in the external iliac basin (one case). CONCLUSION: SLNs detected by our method had micrometastases more frequently than did non-SLNs. Easy detection of micrometastases by immunostaining is only possible with step-serial sectioning of the SLNs.