BACKGROUNDColorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy.

METHODSWe subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs). Isolated cells from PDXs at appropriate tumor size were mingled with Matrigel, and then seeded in ultra-low attachment 96-well plates at four cell densities (500, 1000, 2000, and 4000 single cells/well). Cells were cultured with advanced Dulbecco's Modified Eagle Medium/F12 medium additional with various factors added to maintain tumor's biological traits and growth activity. The growth curves of the four cell densities were measured after 24 h of culture until 25 days. We evaluated the effects of four chemotherapeutic agents on organoid model by the CellTiter-Glo ® Luminescent Cell Viability Assay. Hematoxylin and eosin (H and E) staining of 3D organoids was performed and compared with patient and CRC PDX tissues. Furthermore, immunohistochemistry was performed, in which the organoids were stained with the proliferation marker, Ki-67. During the experimental process, a phase-contrast microscope was used.

RESULTSPhenotype experimental results showed that 3D organoids were tightly packed together and grew robustly over time. All four densities of cells formed organoids while that composed of 2000 cells/well provided an adequate cultivation system and grew approximately 8-fold at the 25 th day. The chemosensitivity of the four conventional drugs was [s]-10-hydroxycamptothecin > mitomycin C > adriamycin > paclitaxel, which can guide clinical treatment. Histological features of CRC patient's tumor tissues and mice tumor xenograft tissues were highly similar, with high-column-like epithelium and extracellular matrix. H and E-stained sections showed heterogeneous cell populations harbored in cancer organoids and were histologically similar to tumor tissues. The proliferation index was only 8.33% within spheroids, which exhibited confined proliferative cells that might be cancer stem cells.

CONCLUSIONSWe successfully constructed a CRC organoid model that grew robustly over 25 days and demonstrated that 2000 cells/well in 96-well plate was a prime seeding density for cells to form organoids. The results confirmed that organoid model can be used for agent screening and personalized medicine.

Adult ; Animals ; Antineoplastic Agents ; therapeutic use ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Colorectal Neoplasms ; drug therapy ; pathology ; Doxorubicin ; therapeutic use ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Mitomycin ; therapeutic use ; Organoids ; drug effects ; pathology ; Paclitaxel ; therapeutic use ; Rectal Neoplasms ; drug therapy ; pathology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays

OBJECTIVE: To explore the feasibility and efficacy of mitomycin C(MMC) in the treatment of airway scarring stenosis. METHOD: The clinical materials of 11 patients with airway stenosis treated with MMC from 2008 to 2012 were analyzed retrospectively,including atresiaofnasopharynx/choanal atresia (2 cases), pharyngostenosis (1 case), and laryngotracheal stenosis (8 cases). All were treated with endoscopic surgery under general anesthesia. Patients received topical application of MMC (0.4 mg/ml) to the lesion for 5 minutes after the scar tissue removed and repeated five times. RESULT: No patients occurred restenosis in 2 months' follow-up postoperative. Two patients with atresiaofnasopharynx/choanal atresia achieved satisfactory ventilation outcome, 8 patients with laryngotracheal stenosis decannulated successfully, 1 patients with pharyngostenosis achieved near normal deglutition. CONCLUSION MMC in endoscopic airway surgery is safe and effective in the treatment of airway stenosis and offers a high success rate for patients with grade 1-2 stenosis. It should be used as a first method in the treatment of airway stenosis.
Adolescent ; Adult ; Child ; Cicatrix ; surgery ; Endoscopy ; methods ; Female ; Humans ; Laryngostenosis ; surgery ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUNDThe recurrence of pterygium after surgery is high. A variety of adjunctive treatment approaches have been developed to improve the clinical efficacy and many related articles have been published. This study aimed to determine the risk for postoperative pterygium recurrence comparing autologous conjunctival transplantation (ACT) versus mitomycin C (MMC).

METHODSRelevant literature published until December 2010 in Medline, Embase, Cochrane, Cochrane library, Science Citation Index, and Google Scholar were searched. Qualified random clinical trial (RCT) studies on the comparison of recurrence rate of pterygium after ACT and MMC treatment were included in this study.

RESULTSEight RCTs with 663 eyes entered the final analysis. The recurrent rate of pterygium was 8.7% (30/343) for ACT and 18.75% (60/320) for MMC. Using fixed-effect meta analysis, we found that the recurrence was significantly lower after ACT than MMC treatment (odds ratio (OR) = 0.40, 95% confidence index (CI), 0.25 - 0.63, P < 0.0001). In sensitivity analyses, we employed random-effects model and excluded studies of low quality or studies in which MMC was administrated after the operation. All the sensitivity analyses confirmed that ACT led to lower recurrence rates than MMC. Sub-group analysis revealed that the recurrence rate was 20.2% (20/99) and 27.65% (26/94) for conjunctival autograft (CA) and MMC respectively, and no significant difference in the recurrence rate was detected (OR = 0.65, 95%CI 0.33 - 1.28, P = 0.22). However, we found that conjunctival limbal autograft (CLA) had lower recurrence rate than MMC (OR = 0.26, 95%CI 0.14 - 0.48, P = 0.0001).

CONCLUSIONCLA has better therapy efficacy against the recurrence of pterygium than MMC.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Conjunctiva ; transplantation ; Humans ; Middle Aged ; Mitomycin ; therapeutic use ; Pterygium ; therapy ; Randomized Controlled Trials as Topic ; Transplantation, Autologous

PURPOSE: To compare the histopathologic and morphologic findings of encapsulated blebs following Ahmed glaucoma valve implantation and primary standard trabeculectomy with mitomycin-C. METHODS: We reviewed the records of patients with otherwise uncontrollable glaucoma who had undergone Ahmed glaucoma valve implantation or trabeculectomy with mitomycin-C. Five eyes that underwent Ahmed valve implantation and three eyes that underwent trabeculectomy needed surgical revision of the initial surgery due to encapsulated bleb development with total loss of function. The surgically removed encapsulated blebs were analyzed macroscopically and microscopically. RESULTS: Removal of the encapsulated bleb was performed at a mean follow-up time of 26.6 +/- 19.4 weeks in the Ahmed valve implantation group and 12.0 +/- 11.4 weeks in the trabeculectomy group. The fibrotic wall of the encapsulated blebs had an overall thickness of 2.48 +/- 0.42 mm in the Ahmed valve implantation group and 1.62 +/- 0.37 mm in the trabeculectomy group. Macroscopically, the coconut flesh-like smooth surface was split into two layers, and the wall of the capsule was thicker in the Ahmed valve implantation group than in the trabeculectomy group. Histopathologically, the fibrotic capsule was composed of an inner fibrodegenerative layer and an outer fibrovascular layer, and there were no histopathological differences between the two groups. CONCLUSIONS: The fibrotic capsule wall was thicker in the Ahmed valve group, but there were no differences in histological findings between the two groups.
Adult ; Blister/*surgery ; Female ; Glaucoma/physiopathology/*surgery ; *Glaucoma Drainage Implants ; Humans ; Infant ; Male ; Middle Aged ; Mitomycin/*therapeutic use ; Nucleic Acid Synthesis Inhibitors/*therapeutic use ; Reoperation ; *Trabeculectomy ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure, including mitomycin (MMC), epirubicin (EPB) and camptothecin (CPT), in the treatment of non-muscle-invasive bladder cancer (NMIBC).

METHODSFrom June 2007 to October 2008, 72 patients with NMIBC, who had tumor recurrence within one year of first-line intravesical chemotherapy, were assigned to 3 groups (24 cases each). Group A received intravesical gemcitabine in a dose of 1000 mg, Group B received 2000 mg gemcitabine, and Group C received original intravesical chemotherapy. The time of reccurrence and adverse effects were recorded.

RESULTSThe 2-year tumor free survival rates of the 3 groups were 66.7%, 75.0% and 45.8%, respectively. The 2-year TFS rate of the patients who received gemcitabine was 70.8%, significantly higher than 45.8% of the patients treated by original chemotherapy. There was one case with renal function impairement in the groups A and B, respectively. There was no significant difference between the rates of low urinary tract symptoms in the 3 groups. No severe hematological side effects were observed in this study.

CONCLUSIONThe intravescal chemotherapy with gemcitabine in patients with recurrent bladder tumor after first-line intravesical chemotherapy is effective and well tolerated, however, renal function should be routinely assessed.

Administration, Intravesical ; Adult ; Aged ; Antibiotics, Antineoplastic ; therapeutic use ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Epirubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Urinary Bladder Neoplasms ; drug therapy ; pathology

OBJECTIVETo evaluate the long-term efficacy of bronchial arterial infusion (BAI) chemotherapy in the treatment of centeral non-small cell lung cancer.

METHODSFifty-eight patients with central non-small-cell lung cancer, who were assessed as difficult operable or non-operable by imaging examination, received BAI of cisplatin, epirubicin and mitomycin alone or in combination. It includes 51 cases of squamous cell carcinoma, 6 cases of adenocarcinoma and 1 case of adenosquamous carcinoma. The cinical stage before BAI wasIIb in 3 cases, IIIa in 26 cases and IIIb in 29 cases. Long term follow-up was conducted and the results were statistically analyzed.

RESULTSThe total effective rate of BAI was 43.1%. The mediam survival (MS) of all 58 patients was 29.1 months. 31 patients after BAI became operable and were resected, had a median survival of 65.2 months. 27 patients after BAI were not resected and had a MS of 15.9 months. There was a significant difference between the patients who had been resected and not. The MS of IIIa stage patients was 39.0 months, and IIIb stage 20.4 months.

CONCLUSIONBronchial arterial infusion chemotherapy is a better choice with a definite efficacy for treatment of center-based NSCLC patients, estimated as difficult operable but without distant metastasis.

Adenocarcinoma ; drug therapy ; pathology ; surgery ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bronchial Arteries ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; surgery ; Cisplatin ; administration & dosage ; Epirubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Infusions, Intra-Arterial ; Lung Neoplasms ; drug therapy ; pathology ; surgery ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Neoplasm Staging ; Survival Rate

BACKGROUND AND OBJECTIVESapylin is one of the biological response modifiers. It has been used in the comprehensive treatment for advanced cancer, and its clinical efficacy has been proved. This study was to evaluate the effect of preoperative intraperitoneal injection of Sapylin in treatment of advanced gastric cancer.

METHODSSeventy-nine patients eligible for radical gastrectomy were randomly divided into the treatment group (Sapylin + mitomycin C, 40 patients) and the control group (mitomycin C alone, 39 patients). In the treatment group, 5 KE Sapylin was injected intraperitoneally 48 h before operation and 4 mg of mitomycin C was injected into peritoneal cavity before the closure of the peritoneum. In the control group, only 4 mg mitomycin C was injected into peritoneal cavity before the closure of the peritonium.

RESULTSThere was no operative mortality or duodenal stump leakage in the two groups. Postoperative complications were anastomotic leakage (2.5%, 1/40) and incision rupture (2.5%, 1/40) in the treatment group, and incision rupture (2.6%, 1/39) in the control group, with no significant difference between the two groups (P > 0.05). The 3-year survival rate was significantly higher in the treatment group than in the control group (76.5% vs. 49.4%, P < 0.05).

CONCLUSIONSPreoperative intraperitoneal injection of Sapylin can raise the 3-year survival rate after radical gastrectomy , without increasing the incidence rate of operative complications. Preoperative intraperitoneal injection of Sapylin is therefore a valuable therapy for advanced gastric cancer in clinic.

Adenocarcinoma ; drug therapy ; pathology ; surgery ; Aged ; Anastomotic Leak ; etiology ; Antibiotics, Antineoplastic ; administration & dosage ; therapeutic use ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Biological Products ; administration & dosage ; isolation & purification ; therapeutic use ; Female ; Follow-Up Studies ; Gastrectomy ; adverse effects ; methods ; Humans ; Injections, Intraperitoneal ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; therapeutic use ; Neoplasm Staging ; Preoperative Period ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; Stomach Rupture ; etiology ; Streptococcus pyogenes ; chemistry ; Survival Rate

OBJECTIVE: To investigate the application of mitomycin in laryngeal surgery. METHOD: Retrospective analysis of the clinical data of 48 patients who had vocal cord lesion involving anterior commissure. The treatment of 30 patients treated with microsurgery and external application of mitomycin, while that of the others were only done with microsurgery. RESULT: Among the 30 patients who were treated with microsurgery and mitomycin, only 2 patients of which showed slight adhesion of anterior commissure after surgery. While in the group of microsurgery, there were 6 patients who had adhesion of anterior commissure adhesion after surgery. CONCLUSION Mitomycin could prevent vocal adhesion after laryngeal surgery.
Adult ; Aged ; Female ; Humans ; Laryngoscopy ; methods ; Larynx ; surgery ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Retrospective Studies

OBJECTIVETo investigate the value of pretreatment and posttreatment changes of apparent diffusion coefficients (ADCs) in predicting response to chemoembolization in liver cancer.

METHODSPatients with liver cancer were examined with diffusion-weighted MRI at two b values (0 and 500 s/mm(2)) before and after chemoemblization. Quantitative ADC maps were calculated using images under b values of 0 and 500 s/mm(2). The mean ADC values of lesions before and after chemoemblization were compared. The correlation of response to chemoembolization with ADC value was analyzed.

RESULTSThe mean value of pretreatment ADC in non-responding lesions were significantly higher than that in the responding lesions (1.687 x 10(-3) mm(2)/s vs. 1.278 x 10(-3) mm(2)/s, P < 0.05). The results of receiver operator characteristic (ROC) analysis showed that when a threshold ADC value was set on 1.618 x 10(-3) mm(2)/s, the sensitivity and specificity for identification of non-responding lesions were 96.0% and 77.8%, respectively. After transarterial chemoembolization, the responding lesions had a significant increase in ADC values than non-responding lesions (32.6% vs. 5.2%, P = 0.025). The results of ROC analysis indicated that when the changes of ADC value for identification of responding lesions before and after transarterial chemoembolization was > or = 16.2%, the sensitivity and specificity were 72% and 100%, respectively. However, no significant change was observed in normal liver parenchyma and spleen (P > 0.05).

CONCLUSIONPretreatment mean ADC value can be used to predict the response to chemoembolization, and for selection of therapy in liver cancer. A significant increase in mean ADC can be observed if the lesions responds to chemoembolization.

Adult ; Aged ; Chemoembolization, Therapeutic ; methods ; Cisplatin ; therapeutic use ; Colonic Neoplasms ; pathology ; Diffusion Magnetic Resonance Imaging ; methods ; Epirubicin ; therapeutic use ; Female ; Humans ; Iodized Oil ; therapeutic use ; Liver Neoplasms ; diagnosis ; secondary ; therapy ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Predictive Value of Tests ; Sensitivity and Specificity ; Stomach Neoplasms ; pathology ; Treatment Outcome

BACKGROUNDRegional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.

METHODSPatients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.

RESULTSThe pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups.

CONCLUSIONSMultiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.

Adenocarcinoma ; drug therapy ; mortality ; pathology ; surgery ; Adult ; Aged ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; therapeutic use ; Humans ; Infusions, Intra-Arterial ; methods ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Metastasis ; Pancreas ; drug effects ; pathology ; surgery ; Pancreatic Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy