Spillage Of Cells Research Articles

Laparoscopic selection for surgery in epithelial ovarian cancer. A short review

The role of laparoscopy as a treatment selection method in ovarian cancer patients is receiving growing attention in surgical practice in both early and advanced-stage disease. When the disease is confined to the ovary, intraoperative laparoscopic assessment of the tumour features is needed to select the best surgical approach in order to prevent intraoperative spillage of cancer cells which would negatively impact patient prognosis. The role of laparoscopy as a disease distribution assessment tool in cases of advanced-stage disease is now accepted by current guidelines as an effective treatment strategy selection. Indeed, a published and validated laparoscopic scoring system, based on laparoscopic assessed intra-abdominal disease dissemination features have been demonstrated to be a reliable predictor of optimal cytoreduction achievement. This subsequently reduces the exploratory laparotomy rate in both primary and interval debulking surgery setting. Furthermore, in cases of recurrent disease, the use of laparoscopy to predict whether complete tumour resection can be achieved is accepted by available guidelines. In this setting, the combination of laparoscopy and imaging techniques to manage platinum sensitive recurrent ovarian cancer cases showed a high accuracy in appropriately selected patients for secondary cytoreductive surgery. In this article we describe the role of laparoscopy in the treatment selection-process in ovarian cancer patients.

Utilization of neoadjuvant stereotactic radiosurgery for the treatment of brain metastases requiring surgical resection: a topic review.

Following surgical resection of brain metastases (BMs), adjuvant stereotactic radiosurgery (SRS) has become the standard of care post-operative cavity irradiation. Recent studies, however, have demonstrated that with the current sequence of surgery and radiation, risk of leptomeningeal disease (LMD) and radiation necrosis (RN) remains high. Pre-operative, or neoadjuvant, SRS (nSRS) has been proposed as an alternative treatment strategy which not only minimizes local recurrence (LR) but also LMD and RN. It is thought that nSRS sterilizes the tumor, allowing for minimal spillage of viable tumor cells during resection, creating less favorable conditions for LMD. Furthermore, nSRS allows for easier contouring and decreased margin irradiation during planning and treatment, respectively, diminishing the risk of symptomatic RN. While nSRS has already been adopted for treating other extra-cranial tumors, its role in treating BMs is yet to be defined. We aim to summarize recent studies in nSRS usage for BMs and the rationale of this treatment strategy. We performed a search for articles regarding nSRS for BMs published in PubMed from 2018 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized a total of 14 retrospective reviews, case series, dose/timing studies, and ongoing Phase II & III clinical trials. In this review, we describe the findings of current studies and identify prospective clinical trials with the aim of understanding the efficacy of nSRS over current treatment standards. Herein, we also discuss the theoretical advantages and limitations of nSRS (both biologic and clinical) to help guide future clinical investigations.

Comment on "Oncological Outcomes After Anastomotic Leakage After Surgery for Colon or Rectal Cancer: Increased Risk of Local Recurrence".

To the Editor, We read with interest the article by Koedam et al.1 demonstrating anastomotic leakage as an independent risk factor for local recurrence after rectal cancer surgery. We congratulate the authors and agree that COLOR trial2 was not powered to be able to extrapolate data on anastomotic leaks and also how in a pre-FOLFOX era the outcomes of stage III colon cancer remained the same irrespective of chemotherapy. However, with respect to the COLOR II observations,3 we have the following concerns. The authors have noted that an ileostomy was performed in 52.4% (44/84) of patients with an anastomotic leak but we observe that “ileostomy” was not included as a factor in the univariate analysis for local recurrence at 5-years follow-up. In COLOR II, performing a diverting ileostomy was left to the discretion of the operating surgeon without being part of a protocol. As seen in COLOR II, preoperative radiation may lead to the increased rate of anastomotic leaks3,4 and not doing a diverting ileostomy can exaggerate sub-clinical leaks which would have not manifested otherwise.5,6 If anastomotic leaks increase the local recurrence,1,7 then the very purpose of neoadjuvant radiation to improve local control in rectal cancers would be defeated. In today’s era, to facilitate the timely administration of the adjuvant treatment and hence further decrease the recurrence rates, an ileostomy may at times prove beneficial. The authors, in the discussion, propose that increased recurrences after anastomotic leaks may be attributed to a delay in adjuvant chemotherapy (although rightly stated as not applicable to COLOR II). This reasoning may have been applicable if there were an increase in distant recurrences in addition to the local recurrences, which is not the case. The authors have referred to a hypothesis of spillage of cancer cells into the peritoneal cavity during the surgery and adhesion of tumor cells due to the inflammatory response of the leak. If this hypothesis is to be believed then the incidence of distant peritoneal failure should also be seen along with or apart from local recurrences. Anastomotic leaks in this analysis were not seen to cause seeding of distant peritoneal sites. Also, we observe that 5 of 23 patients (25.2%) with positive resection margins had a local recurrence at 5 years and 9 of 84 patients (13.3%) with anastomotic leaks had a local recurrence at 5 years. However, it would be interesting to note how many patients with positive resection margins had anastomotic leaks. We are not sure what could be the likely explanation for the increased recurrences in patients who had anastomotic leaks but this finding gives grounds to further evaluate total neoadjuvant treatment to treat rectal cancers,8 other than evaluating this important observation in a trial powered to study the same.

Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer.

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18–60) and 78 (48–102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis.

Challenges in Diagnosis and Prevention of Iatrogenic Endometriosis as a Long-Term Surgical Complication after C-Section.

Endometriosis is a gynecological condition caused by the development of endometrial tissue outside the uterine cavity. Naturally, it commonly occurs at locations such as the ovaries and pelvic peritoneum. However, ectopic endometrial tissue may be discovered outside of the typical sites, suggesting the possibility of iatrogenic seeding after gynecological operations. Based on this hypothesis, we developed a study aiming to establish the root cause of atypical implantation of endometrial foci, as the main end point, and to determine diagnostic features and risk factors for this condition, as a secondary target. The research followed a retrospective design, including a total of 126 patients with endometriosis who met the inclusion criteria. A group of 71 patients with a history of c-section was compared with a control group of patients with endometriosis and no history of c-section. Endometriosis that developed inside or in close proximity to surgical incisions of asymptomatic patients before surgical intervention was defined as iatrogenic endometriosis. Compared with patients who did not have a c-section, the c-section group had significantly more minimally invasive pelvic procedures and multiple adhesions and endometriosis foci at intraoperative look (52.1% vs. 34.5%, respectively 52.1% vs. 29.1%). The most common location for endometriosis lesions in patients with prior c-section was the abdominal wall (42.2% vs. 5.4%), although the size of foci was significantly smaller by size and weight (32.2 mm vs. 34.8 mm, respectively 48.6 g vs. 53.1 g). The abdominal wall endometriosis was significantly associated with minimally invasive pelvic procedures (correlation coefficient = 0.469, p-value = 0.001) and c-section (correlation coefficient = 0.523, p-value = 0.001). A multivariate regression analysis identified prior c-section as an independent risk factor for abdominal wall endometriosis (OR = 1.85, p-value < 0.001). We advocate for strict protocols to be implemented and followed during c-section and minimally invasive procedures involving the pelvic region to ensure minimum spillage of endometrial cells. Further research should be developed to determine the method of abdominal and surgical site irrigation that can significantly reduce the risk of implantation of viable endometrial cells. Understanding all details of iatrogenic endometriosis will lead to the development of non-invasive disease diagnosis and minimally invasive procedures that have the potential to reduce postoperative complications.

The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5′-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

Purse-string failure at the beginning of the learning curve in transanal total mesorectal excision

Background: Transanal total mesorectal excision (TaTME) is a novel technique developed to overcome the difficulties and improve the oncological results in patients with narrow pelvis and bulky mesorectum. Аchieving an air-tight purse-string suture is а crucial step in an oncologically safe TaTME and could be challenging at the beginning of the learning curve. Purse-string failure could theoretically increase the risk of local recurrence by tumor cell spillage and aerosolization of these tumor cells by the transanal insufflation.

A simple technique of vaginal cuff closure to prevent tumor cell spillage in laparoscopic radical hysterectomy for uterine cervical cancer.

The Laparoscopic Approach to Cervical Cancer (LACC) trial, a prospective randomized phase III clinical trial reported in 2018, unexpectedly showed inferior oncologic outcomes in laparoscopic radical hysterectomy (LRH) for cervical cancer compared with those in open surgery. It was proposed that the spillage of tumor cells into the peritoneal cavity might cause the inferiority of LRH. It has been suggested, based on retrospective studies, that transvaginal closure of the vaginal cuff before the colpotomy part of the surgery may prevent this. Before starting colpotomy, we closed the vaginal cuff transvaginally. After the assessment of the cutline of the vagina, the vaginal mucosa is pulled at the eight sites using the sutures. The four pairs of sutures on the diagonal line are ligated. A purse string suture is additionally placed on the vaginal mucosa to close the vaginal cuff completely. After that, we start the intracorporeal colpotomy using a vaginal pipe. Our technique is simple and quick. The blood loss during the transvaginal procedures is minimal. The use of the vaginal pipe helps keep the vaginal cuff closed during the colpotomy. Our technique may be an alternative to the conventional approach closing the vaginal cuff.

Vaginal Closure Before Colpotomy with an Endo-Stapler to Prevent Tumor Spillage in Laparoscopic Surgery for Gynecological Malignancy.

Background and Objectives:The aim of this study was to define new techniques for performing vaginal closure with endo-staplers to prevent tumor spillage during laparoscopic surgeries for endometrial cancer and early stage cervical cancer.Methods:Thirteen patients were retrospectively studied for the use of endo-staplers for vaginal closure before colpotomy during laparoscopic surgeries for endometrial cancer and early stage cervical cancer to prevent tumor spillage.Results:There were no short-term or any long-term complication related to the use of the endo-staplers for colpotomy in the surgeries included in this study.Conclusion:Use of the endo-staplers to close the vagina before colpotomy according to the technique described is safe and feasible, with prevention of gross spillage of any malignant cells in the peritoneal cavity or vagina, which will further have a favorable oncologic outcome.

BIOM-03. INVASIVE HISTOPATHOLOGY DRIVES POOR OUTCOMES IN SURGICALLY RESECTED BRAIN METASTASES

Abstract BACKGROUND Surgery as a single modality for the treatment of brain metastases (BrM) results in local recurrence (LR) in 60% of patients. These failure rates are reduced by half with post-operative radiotherapy. The non-invasive nature of BrM has led to the assumption that local recurrence is caused by spillage of cancer cells into the surgical cavity at the time of surgery. We present evidence suggesting that invasion of metastatic cancer cells into the adjacent brain is present in the majority of BrM and is associated with LR, leptomeningeal metastasis (LM), and overall survival (OS). METHODS We assessed the histopathological growth pattern (HGP) of 164 surgically resected BrM. HGP was correlated with LR, LM and OS. Single-cell transcriptomics (scRNAseq) was performed on 15,615 cells from metastasis center (MC) and surrounding brain (SB) adjacent to the tumor. N=30 orthotopic patient-derived xenograft models (OPDX) were established from BrM. RESULTS 56/164 (34%) BrM specimens showed a minimally invasive (MI) HGP between the tumor and adjacent brain while 108/164 (66%) showed significant invasion of tumor lobules or single-cells into the brain (HI-HGP). HI-HGP was associated with LR, LM and shortened OS in BrM patients. scRNAseq identified abundant cancer cells in SB that overexpressed pathways and genes involved in cell survival and stress adaptation compared to matched cancer cells in MC. Validation of these targets with immunohistochemistry in patient and OPDX tissues revealed cold-inducible RNA binding protein (CIRBP) overexpression in HI-HGP patient and OPDX BrM. Modulation of CIRBP expression in OPDX and cell line models of HI-HGP BrM delayed BrM progression and extended OS. CONCLUSION HI-HGP is a poor prognostic indicator in patients with surgically resected BrM, establishing HGP as an important prognostic factor that should be considered by clinicians treating BrM patients. We identify CIRBP as a functional mediator of this process.

Aiming for Recurrence-Free MI-RH/RT for Early Invasive Cervical Cancer - Focusing on Complete Resection and No-Touch Isolation Techniques 1

Video Objective To demonstrate techniques to regulate and improve the safety and completeness of laparoscopic and robotic radical hysterectomy/radical trachelectomy (L-RH/RT+R-RH/RT=MI-RH/RT) for early invasive cervical cancer. We will present our techniques and skills as well as data on our long-term outcomes for MI-RH/RT patients. Setting Urban general hospital in Japan. Interventions 170 early invasive cervical carcinoma stage IA1(LSVI+)-IB1 who underwent MI-RH/RT between 2006-2015 were reviewed. Cases who underwent neo-adjuvant therapy were excluded from this study. In laparoscopy, knowledge laparoscopic anatomy and how to dissect are the most important points for reaching the goals of the surgery. Setting landmarks for dissection boundaries ensures completeness of dissection. For our type C radical hysterectomy/ trachelectomy, our goal is to remove the full length of the cardinal ligament. This is to prevent recurrence. To prevent the scattering of tumor cells, we create a vaginal cuff as an initial stage of our procedure and don't use a uterine manipulator as there is the concern that this could stimulate any tumors in the vicinity. When extracting the specimen, we use a large protection bag. This bag prevents spillage of tumor cells in the abdominal cavity and prevents possible port site/ extraction site contamination. Of the patients included in this study, disease-free survival is 97.1% and the 5 year overall survival in 98.2%. Conclusion In our retrospective study, minimally invasive approach for early-stage non-bulky cervical cancer is feasible and safe in terms of oncological outcomes.

Intrauterine Fluid Instillation and Transtubal Flow: A Randomized Controlled In vitro Trial Comparing Gel and Water.

Background:Possible transtubal spillage of malignant cells is a major concern in fluid instillation sonography, as it is in hysteroscopy. This study aims to compare the transtubal flow of gel and saline and validate the clinical hypothesis that application of fluids with higher viscosity causes less spillage.Methods:Randomized controlled in vitro trial comparing gel and saline infusion on 15 tissue specimens after hysterectomy with bilateral salpingectomy. Instillations are performed with saline and gel dyed with a 1% ink solution. Qualitative assessment of tubal spill is investigated as primary outcome. Secondary outcomes are instillation-volume and -pressure, assessed by measuring endometrial cavity dilation at in vitro ultrasound examination and subjective numeric 10-point scoring of the instillation pressure by a dedicated examiner.Results:Tubal flow was more often observed during saline instillation (odds ratio 4.88, P = 0.008). Median subjectively assessed instillation pressures were nine arbitrary units for gel and three for saline (P < 0.001). Tubal flow occurred from 2 cc onward in the saline group versus five cc in the gel instillation group. Cavitary dilation did not differ between both groups.Conclusion:Gel instillation sonography is in vitro associated with less tubal flow and therefore could be a safer diagnostic test compared to saline infusion sonography or hysteroscopy. In vivo studies are necessary to confirm these results.

Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer.

Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis.

Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff - a multicenter analysis.

Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2-86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1-288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.

Does transrectal ultrasonography-guided biopsy of the prostate lead to possible further metastasis via circulating tumor cells?

Background/aimWe evaluate whether transrectal ultrasonography (TRUS)-guided prostate biopsy might lead to spillage of tumor cells into peripheral blood as a result of disruption of the epithelial barrier and ultimately result in metastasis. Materials and methodsEighty-eight patients underwent TRUS-guided prostate needle biopsy due to prostate-specific antigen (PSA) increase or abnormal digital rectal examination at the Samsun Research and Training Hospital (Samsun, Turkey) between April 2016 and September 2018. Approximately 10 mL of whole blood was collected from patients before, 1 week after, and 1 month after biopsy. Samples were analyzed for CD117 positivity and prostate-specific membrane antigen (PSMA) levels using flow cytometry. Patients with pathologically determined prostate cancer and without CD117 positivity before biopsy were included in the study. The study group thus consisted of 55 patients.ResultsSubjects’ PSA levels ranged from 2.3 to 40.0 ng/mL (median: 7.9 ng/mL), and their Gleason score was a median of 7 (range: 5–9). PSMA levels ranged between 9.3 ng/mL and 118.5 ng/mL and CD117 antigen levels between 0 and 5. We detected no CD117-positive cells in blood samples collected 7 days or 1 month after biopsy.ConclusionWe detected no circulating tumor cells in the peripheral circulation following biopsy. Prostate needle biopsy seems to be a safe method in terms of spillage of tumor cells into blood circulation as a possible cause of further metastasis.

Preoperative gastric lavage in gastric cancer patients undergoing surgical, endoscopic or minimally invasive treatment: An oncological measure preventing peritoneal spillage of intragastric cancer cells and development of related metastases

In addition to classical metastatic pathways, recently gastric cancer was described having an alternative route called “endoluminal exfoliation”. Provisional analyses demonstrated, in fact, this kind of shedding is associated with several clinico-pathological features indicative of aggressive behavior and resulted to be an independent prognostic factor entailing poor prognosis. Compared with non-sowing counterparts, in fact, patients affected with exfoliating early and advanced gastric carcinomas met with shorter overall survival, disease free survival, progression free survival and time to tumor progression. In spite of these interesting results, however, the clinico-pathological and oncological significance of this unconventional metastatic route is still to be clarified. Such an investigation is further urged by the increasing widespread employment of minimally invasive treatments for gastric cancer which include a wide spectrum of intragastric interventions and maneuvers. Indeed, endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, intragastric laparoscopic surgery and hybrid procedures all take place inside of the stomach. However, iatrogenic perforations can occur during execution of these treatments leading to spillage of malignant cells from gastric to the peritoneal cavity or trocar insertion sites. Furthermore, many other gastric conditions and interventions can collide with endogastric presence of floating cancer cells: spontaneous ulceration or perforation, laparotomy surgery, gastrointestinal occlusion, diverticula. Viability, migration and intraluminal transportability of the intragastric floating cancer cells represents another original and intriguing topic. All these considerations led us to entertain the hypothesis that removing the exfoliated cancer cells from the gastric lumen could save patients from the dreaded potential risk of spillage. Performing gastric lavage before starting any kind of tumor intervention could be the most appropriate procedure to adopt with prophylactic intent. Should our speculation prove to be clinically significant, preoperative gastric lavage should be pointed out as a simple but cogent method useful for preventing oncological mishaps such as spillage of gastric cancer cells and development of related recurrences or metastases.

Pathophysiology and therapeutic strategies for peritoneal recurrence after gastric cancer surgery.

4050 Background: We recently showed that cancer cells, with proliferative and tumorigenic potential, can spill into the peritoneal cavity during curative (R0) gastric cancer (GC) surgery, which is associated with peritoneal recurrence (PM). To elucidate the pathophysiology of PM, the relationship between spilled cancer cells and cancer stem cells was evaluated. Furthermore, to identify a therapeutic strategy for PM, the prognostic impact of hyperthermic intraperitoneal chemotherapy (HIPEC) following GC surgery with spillage of cancer cells was evaluated. Methods: Patients with advanced GC (≥pT2 [MP]) who underwent R0 gastrectomy between 2010 and 2015 were enrolled. Ninety-four consecutive patients with negative results in peritoneal cytology and cancer cell culture (CCC [-]) following peritoneal washing (PW) before GC surgery were included. Spilled cancer cells in PW after GC surgery (PW-Post) were examined to identify any CD44-positive cancer stem-like cells associated with cancer metastasis. Based on the PW-Post CCC results, associations between HIPEC and recurrence-free survival (RFS), or overall survival (OS) were evaluated. HIPEC was performed following GC surgery using CDDP, MMC, and 5-FU in 5 L saline maintained at 42˚C for 30 min. Results: Spilled cancer cells included CD44+ cancer stem-like cells. In 48 patients with PW-Post positive CCC (CCC [+]), the number of patients with pStage I, II, and III were 4, 7, and 15, respectively, in those who received HIPEC (n = 26), and 3, 9, and 10, respectively, in those who did not (n = 22). Among patients with CCC (+), the 5-year peritoneal RFS, hepatic RFS, and lymph node RFS rates were 93.3%, 100%, and 68.5%, respectively, in patients who received HIPEC, and 56.7%, 35.6%, and 66.7%, respectively, in those who did not ( P = 0.008, P = 0.008, and P= 0.24, respectively). Among patients with PW-Post CCC (-), none developed recurrence, regardless of whether they received HIPEC (n = 28) or not (n = 18). Conclusions: The results show that PW-Post CCC is a promising predictive biomarker for recurrence after R0 GC surgery. Adjuvant HIPEC performed with R0 GC surgery showed preventive effects on peritoneal and hepatic recurrence and survival benefits for patients with PW-Post CCC (+).

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer.

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Disseminated leiomyoma cells can be identified following conventional myomectomy.

Uncontained morcellation of leiomyomas during laparoscopic surgery has recently been discouraged, as undetected malignant tumours, namely leiomyosarcomas, could be fragmented which may result in upstaged disease. However, enucleating leiomyomas per se may be inappropriate from an oncological perspective because complete, radical resection of malignant tumours to prevent further tumour growth or recurrence is not achieved. Thus, the aim of this study was to determine whether spillage of leiomyoma cells occurs during laparotomic myomectomy. Observational study. Tertiary academic centre in the Netherlands. Women undergoing laparotomic myomectomy were included in the study. Peritoneal abdominal washings were obtained on two occasions during the myomectomy procedure; the first one immediately after opening the abdomen and the second one after resection of the leiomyoma(s). Cytological evaluation of the fluids was performed. The presence of leiomyoma cells in any of the washings. Five patients were included in this pilot study. All first washings were negative for leiomyoma cells. However, cytology positive for the presence of leiomyoma cells was found in three of the five second, post-myomectomy washings. Tissue spillage from leiomyoma(s) occurs during conventional open myomectomy. The clinical relevance of tissue dissemination after myomectomy is unclear but it cannot be excluded that this may negatively affect the patient's outcome if there is malignant change within the enucleated leiomyoma(s). Therefore, it is questionable whether morcellation in specially designed containment bags after laparoscopic myomectomy, guarantees any additional oncological safety. Even during conventional myomectomy, tissue spillage occurs during resection of leiomyoma(s).

Single-site in-bag morcellation achieved via direct puncture of the pneumoperitoneum cap, a cordless electric morcellator, and a 5-mm flexible scope

ObjectiveTo evaluate a modified single-access method of contained power morcellation performed with a single-access laparoscopic device and a new cordless electric morcellator. The study was a preliminary assessment of the feasibility and safety of the new technique. Study designA single university hospital observational study involving patients who underwent either laparoscopic myomectomy or laparoscopic hysterectomy. We evaluated the operative results, time required for the contained morcellation, any occurrence of bag leakage, and any complications. ResultsThe new contained power morcellation technique was applied in 12 patients (9 undergoing laparoscopic myomectomy and 3 undergoing laparoscopic hysterectomy). The mean bag introduction time was 21.8min (range, 14–37min); mean in-bag morcellation time was 11.5min (range, 1–26min); and mean total morcellation time was 36.8min (range, 19–66min). Visual inspection revealed no bag damage. There were no postoperative complications. ConclusionSingle-site in-bag morcellation performed with our new technique requires neither bag penetration nor piercing with a trocar and thus may prove beneficial for preventing spillage and dissemination of unwanted cells and tissue.