Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

CNSI (50 mg/dose) was produced by Chongqing Lesmei Pharmaceutical Co., Ltd.: Carbon nanoparticles were marked in the endoscopy division 1 day before surgery, and CNSI was injected submucosally at 4 points (proximal side, distal side, and left and right sides) 0.5-1 cm from the tumor edge under endoscopy. The test dose for each point was approximately 0.25 ml.

ICG (25 mg/dose) was produced by Dandong Yichuang Pharmaceutical. ICG was marked in the endoscopy division 1 day before surgery and injected submucosally at 4 points (proximal side, distal side, and left and right sides) 0.5-1 cm from the tumor edge under endoscopy. The test dose for each point was approximately 0.5 ml.

Both procedures were performed by a designated medical practitioner.

carbon nanoparticles

Indocyanine green

Qun Zhao

The purpose of this study is to assess the efficacy and safety of carbon nanoparticle suspension injection and indocyanine green tracer-guided lymph node dissection during gastrectomy in patients with gastric cancer

Da Vinci robot surgery XI system has fluorescence imaging function, which can realize indocyanine green lymph node tracking navigation technology in the operation. At the same time, the lymph node tracking effect of nano carbon suspension injection is not affected by equipment. The flexible mechanical arm of Da Vinci robot combined with the application of lymph node tracing technology makes the lymph node dissection of gastric cancer surgery more thorough, and also reduces the difficulty of surgery. Indocyanine green navigational lymphadenectomy can also be performed by fluorescence laparoscopy. By comparing the two tracer techniques, the lymph node tracer technique which is more suitable for robot or laparoscopic surgery system is selected to provide help and choice for clinical surgeons.

Effect of CNSI vs. ICG in Lymph Node Tracing During Gastrectomy

A Prospective Randomized Controlled Study of the Efficacy of Carbon Nanoparticles Versus Indocyanine Green in Robotic or Laparoscopic Gastrectomy

Compare total number of retrieved lymph nodes in both group.

The number of black-stained/fluorescent lymph node in experimental group is divided by the total number of lymph nodes in active experimental group

The number of positive lymph nodes in black-stained/fluorescent lymph nodes is divided by the number of total black-stained/fluorescent lymph nodes in experimental group

The number of negative lymph nodes in black-stained/fluorescent lymph nodes is divided by the number of total black-stained/fluorescent lymph nodes in experimental group

The number of negative lymph nodes in not black-stained/fluorescent lymph nodes is divided by the number of total not black-stained/fluorescent lymph nodes in experimental group

The number of positive lymph nodes in not black-stained/fluorescent lymph nodes is divided by the number of total not black-stained/fluorescent lymph nodes in experimental group

Compare number of positive lymph nodes in both group.

This is for the early postoperative complication and mortality, which defined as the event observed within 30 days after surgery.

Disease-free survival is calculated from the day of surgery to the day of recurrence (When the specific date of recurrence of the tumor is unknown, the ending point is the date of death due to tumor causes). In the event that neither death nor recurrence of the tumor are observed, the end point is the final date that a patient is confirmed as relapse-free.

Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type.

Postoperative lymph node anatomy duration

Hebei Medical University

Principal Investigator

Gland and Hormone Related Diseases

Thyroid Neoplasms

Thyroid Diseases

Thyroid Cancer, Papillary

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma

Adenocarcinoma, Papillary

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Papillary Thyroid Carcinoma

0.1 ml of CN suspension was injected per spot into the tissue surrounding the tumor using a skin test syringe. Two or three randomly selected spots were injected slowly for each tumor, and the total amount injected was no more than 0.5 mL per lobe.

Wenbin Yu, MD

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer.

The most common site of PTC nodal metastases is the central neck, which has a reported rate of lymph node metastases as high as 50%\~70%.

Central neck dissection has important value to ensure accurate clinical staging and surgical planning.

As a novel lymphatic tracer, carbon nanoparticles (CN) have been applied successfully in the detection of sentinel lymph nodes in breast and gastric cancers, while not been used as a lymphatic tracer for PTC. The goal of this study was to evaluate whether the use of CN facilitates the detection of lymph nodes, increases the number of metastatic lymph nodes removed, accurately reflects the metastatic condition of the central neck, and has the potential to protect the parathyroid glands.

Thyroid cancer is the most common endocrine malignancy. It is estimated that 96% of all new endocrine organ cancers will originate from the thyroid gland, resulting in approximately 63,000 new cases in 2014 in the US1. Among them, papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, accounting for more than 90% of all thyroid cancers. The incidence of PTC has been increasing in recent years, largely because of advances in early detection with ultrasonography and fine-needle aspiration biopsy1-4. The most effective treatment for PTC is the complete removal of the primary tumor and the metastatic regional lymph nodes, which is a prerequisite for other adjuvant therapies. Cervical lymph node metastases are quite common in PTC and have been reported to occur in 12-81% of patients with PTC5. The most common site of PTC nodal metastases is the central neck, which has a reported rate of lymph node metastases as high as 50%\~70%5. Lymph node metastases in this area are difficult to identify preoperatively because the lymph nodes typically do not appear abnormal on preoperative imaging6,7.

Routine dissection of the central neck compartment is still controversial due to uncertain prognostic value of preserving clinically non-apparent lymph node metastasis1,8, central neck dissection has important value to ensure accurate clinical staging and surgical planning. According to previously published data, prophylactic central dissection has been suggested to improve disease-specific survival and to decrease local recurrence9,10 as well as post-treatment thyroglobulin levels9,11. Neck dissection also informs postoperative treatment, follow-up programs, assessment of recurrence risk, and prognosis12. However, routine neck dissection is controversial because of the uncertain effect on prognosis of clinically non-apparent lymph node metastases and because of complications, such as damage to the parathyroid glands, hypoparathyroidism, temporary/permanent recurrent laryngeal nerve injury, and tracheal or esophageal injury, that may profoundly influence a patient's qual¬ity of life.

Methylene blue has been used in the detection of sentinel lymph nodes in thyroid cancer, but methylene blue can also stain parathyroid glands, thyroid tissue, and fat, which can make the anatomic boundaries unclear and thereby restrict the use of methylene blue in PTC. As a novel lymphatic tracer13,14, carbon nanoparticles (CN) have been applied successfully in the detection of sentinel lymph nodes in breast and gastric cancers, while not been used as a lymphatic tracer for PTC. Thus, investigators hypothesized that CN may have clinical value in thyroid cancer as a novel lymph node tracer to guide central neck dissection. The goal of this study was to evaluate whether the use of CN facilitates the detection of lymph nodes, increases the number of metastatic lymph nodes removed, accurately reflects the metastatic condition of the central neck, and has the potential to protect the parathyroid glands. In this study, investigators evaluated the clinical value of CN in acquiring a more accurate reflection of the central neck lymph node status and in guiding central neck dissection.

Potential Role for Carbon Nanoparticles to Guide Central Neck Dissection in Patients With Papillary Thyroid Cancer

Peking University Cancer Hospital & Institute

department of head neck

Carbon Nanoparticles could be used in this arm.The drug is injected into the subserosa of stomach.Injections of 1.0 ml of Carbon Nanoparticles (0.2 ml in each cardinal point adjacent to the lesion) will be performed about 10 minutes before surgery.Then,gastrectomy with D2 dissection will be performed.

Gastrectomy with D2 dissection will be performed in the control arm,no Carbon Nanoparticles or other coloring materials used

Carbon Nanoparticles will be injected into the subserosa of stomach around the tumor.Gastrectomy with D2 dissection will be performed after the injection.

Carbon Nanoparticles

In the control arm,Gastrectomy with D2 dissection will be performed directly,without any coloring materials.

Gastrectomy with D2 dissection

Jiafu Ji, master

Carbon Nanoparticles (CNP),with a mean size of 150 nm,can be taken up selectively by lymphatics after injection into the tissue and draining regional lymph nodes are thereby colored black,which may provide surgeons the guidance to lymph node dissection and help them harvest lymph nodes after surgery,especially some small ones. but there was insufficient evidence to justify its efficacy for those purposes.Therefore,the investigators carried out a prospective randomized controlled trial on lymph node vital staining for lymph node dissection and harvesting in advanced gastric cancer to test this idea.

Clinical Study on the Harvesting Lymph Nodes With Carbon Nanoparticles for Advanced Gastric Cancer

Clinical Study on the Harvesting Lymph Nodes With Carbon Nanoparticles for Advanced Gastric Cancer：a Prospective Randomized Study

Peking University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Pharmaceutical Solutions

All Drugs and Chemicals

After pneumoperitoneum is established and laparoscopic instruments are prepared, according to National Comprehensive Cancer Network (NCCN) guidelines, 1ml diluted ICG solution (25 mg /10 ml) is injected into the submucosa around tumor at 3 and 9 o'clock of the cervix (2ml totally) with 1ml syringe. ICG should be slowly injected to avoid drug leakage. Intratumoral and deep cervical stroma injection should be avoided. The retroperitoneum is dissected immediately after injection under the multimodel observation of fluorescence laparoscopy. Search the fluorescent labeled lymphatics from bilateral parametrium to iliac vessels. The diffusion of ICG is rapid , and it is easy to spread to the next stations lymph nodes. The first fluorescent labeled lymph nodes on each lymphatic drainage pathway are identified as SLNs, other than all fluorescent lymph nodes. All detectable SLNs and enlarged or suspicious nodes regardless of mapping are resected for pathological examination alone.

Carbon nanoparticles

After pneumoperitoneum is established and laparoscopic instruments are prepared, according to NCCN guidelines, 0.5ml(25mg) carbon nanoparticle solution (the dose was from our retrospective study) is injected into the submucosa around tumor at 3 and 9 o'clock of the cervix (1ml totally) with 1ml syringe. Carbon nanoparticle should be slowly injected to avoid drug leakage. Intratumoral and deep cervical stroma injection should be avoided. The retroperitoneum is dissected immediately after injection. Search the black lymphatics from bilateral parametrium to iliac vessels. Because there is no fluorescence penetration as ICG, the black lymphatic vessels should be dissected carefully.The first black lymph nodes on each lymphatic drainage pathway are identified as SLNs, other than all black lymph nodes. All detectable SLNs and enlarged or suspicious nodes regardless of mapping are resected for pathological examination alone.

Bin Li, M.D.

Hongyi Hou, M.D.

The metastasis rate of pelvic lymph node in early cervical cancer is low. Systemic lymph node resection is traumatic and has many complications. Sentinel lymph node (SLN) biopsy can effectively avoid unnecessary lymph node dissection, which has been recommended in clinical guidelines. Indocyanine green(ICG) fluorescence imaging as the method of SLN mapping is recommended in international guidelines. However, the imaging equipment is very expensive which limits the popularization of ICG in different medical centers of various surgical volumes. Carbon nanoparticle is an innovative tracer without any special imaging equipment for SLN mapping in China. Some retrospective researches have proved that carbon nanoparticle is effective, simple, economic and suitable for popularization in different medical centers. In this study, a prospective randomized controlled trial will be conducted to analyze the non-inferiority of carbon nanoparticles compared to ICG, and to verify the application value of carbon nanoparticles. 144 cervical cancer patients with stage IB1 (FIGO2018) will be prospectively enrolled and randomly divided into two groups (R = 1:1). 72 patients will undergo SLN biopsy with carbon nanoparticles and 72 patients will be mapped by ICG. The primary endpoint is overall SLN detection rate. The secondary endpoints include bilateral SLN detection rate, the number of SLN detected, sensitivity, false negative rate and negative predictive value of SLN biopsy. Diagnostic accuracy will be evaluated at both pelvis and patient levels. What's more, SLN pathological ultrastaging will be conducted to increase the diagnostic accuracy. The hypothesis of this study is that the overall SLN detection rate by carbon nanoparticles is not inferior to that using ICG. And the differences of bilateral SLN detection rate, sensitivity, false negative rate and negative predictive value between two groups are not significant.

This is a prospective randomized controlled non-inferiority trial. Patients with early stage cervical cancer who met the inclusion criteria are divided into carbon nanoparticle group and ICG group by block random method. It is assumed that the overall SLN detection rate was PT (90%) in experimental group(carbon nanoparticle) and was PC (85%) in control group (ICG). The non-inferiority threshold Δ is -10%. The type I error and type II error of the hypothesis test are set as 0.05 and 0.2 respectively. The sample size is 60 cases in each group calculated by"Non inferiority tests for two proportions"method of Power Analysis and Sample Size (PASS) Software 11.0. After calculation, considering the 20% shedding rate, the sample size is 144 totally. There are 72 cases in experimental group and 72 cases in control group. Radical hysterectomy and systemic pelvic lymph node dissection are conducted after SLN resection, and paraaortic lymph node biopsy is conducted when necessary. Sentinel lymph nodes will be cut at 2-mm intervals perpendicular to the long axis in a bread-loaf fashion. Sentinel lymph nodes are then fixed in formalin and embedded in paraffin. Routine hemotoxin \& eosin(H\&E) staining is used for each SLN. Subsequent ultrastaging is performed if the initial H\&E assessment is negative. SLN ultrastaging is performed by cutting three 5-μm sections at two levels, 50-μm apart, from each paraffin block of negative SLN. At the first level, two adjacent 5-μm sections are stained with H\&E and immuno-histochemistry using the anti-cytokeratin AE1:AE3, respectively. At the second level, one 5-μm section is evaluated by H\&E staining. Nonsentinel lymph nodes are bisected parallel to the long axis and stained with H\&E staining.Nodal metastases are classified as (1) isolated tumor cells (ITCs) (single cells or clusters ≤ 0.2mm in largest dimension),(2) micrometastases (tumor deposits 0.2mm-2 mm), or (3) macrometastases (tumor deposits \> 2mm). All pathological reviews will be finished by two independent gynecologic pathologists in the Department of Pathology of Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College. A third senior pathologist is invited to decide the diagnosis when discordance occurs.

Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer

A Randomized Controlled Comparison Study of Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer

The time from the beginning of the operation to the end of the operation.

The amount of bleeding during the operation.

Adverse events, such as allergy, are caused by injection of tracers and defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

In this study, operative complications are defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

The percentage of patients with successfully detected SLNs in all eligible patients.

The percentage of patients with successfully detected SLNs in both sides of the pelvis in all eligible patients

The numbers of detected SLNs are calculated by the pathologist.

Distribution of SLNs in pelvic and abdominal cavity, including external iliac, obturator fossa, internal ilia, deep inguinal, common iliac, presacral, inferior vena cava, para-aortic, and parametrial regions.

The percentage of patients or pelvises with positive SLNs in pathological examination among those with positive pelvic lymph nodes.

The percentage of patients or pelvises with negative SLNs in pathological examination among those with positive pelvic lymph nodes.

The percentage of patients or pelvises with negative pelvic lymph nodes among those whose SLNs were negative in pathological examination.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of CNSI vs. ICG in Lymph Node Tracing During Gastrectomy	NCT05229874	Gastric Cancer	carbon nanopart... Indocyanine gre...	18 Years - 75 Years	Hebei Medical University
Potential Role for Carbon Nanoparticles to Guide Central Neck Dissection in Patients With Papillary Thyroid Cancer	NCT02724176	Thyroid Cancer	carbon nanopart...	18 Years - 75 Years	Peking University Cancer Hospital & Institute
Clinical Study on the Harvesting Lymph Nodes With Carbon Nanoparticles for Advanced Gastric Cancer	NCT02123407	Advanced Gastri...	Carbon Nanopart... Gastrectomy wit...	20 Years - 80 Years	Peking University
Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer	NCT05167149	Cervical Cancer...	Carbon nanopart... Indocyanine gre...	18 Years - 70 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer	NCT05167149	Cervical Cancer...	Carbon nanopart... Indocyanine gre...	18 Years - 70 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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