Synthesis of shape-programmable elastomer for a bioresorbable, wireless nerve stimulator.

Materials that have the ability to manipulate shapes in response to stimuli such as heat, light, humidity and magnetism offer a means for versatile, sophisticated functions in soft robotics or biomedical implants, while such a reactive transformation has certain drawbacks including high operating temperatures, inherent rigidity and biological hazard. Herein, we introduce biodegradable, self-adhesive, shape-transformable poly (L-lactide-co-ε-caprolactone) (BSS-PLCL) that can be triggered via thermal stimulation near physiological temperature (∼38 °C). Chemical inspections confirm the fundamental properties of the synthetic materials in diverse aspects, and study on mechanical and biochemical characteristics validates exceptional stretchability up to 800 % and tunable dissolution behaviors under biological conditions. The integration of the functional polymer with a bioresorbable electronic system highlights potential for a wide range of biomedical applications.

Highly Elastic, Bioresorbable Polymeric Materials for Stretchable, Transient Electronic Systems.

Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues.

Soft, Long-Lived, Bioresorbable Electronic Surgical Mesh with Wireless Pressure Monitor and On-Demand Drug Delivery.

Current research in the area of surgical mesh implants is somewhat limited to traditional designs and synthesis of various mesh materials, whereas meshes with multiple functions may be an effective approach to address long-standing challenges including postoperative complications. Herein, a bioresorbable electronic surgical mesh is presented that offers high mechanical strength over extended timeframes, wireless post-operative pressure monitoring, and on-demand drug delivery for the restoration of tissue structure and function. The study of materials and mesh layouts provides a wide range of tunability of mechanical and biochemical properties. Dissolvable dielectric composite with porous structure in a pyramidal shape enhances sensitivity of a wireless capacitive pressure sensor, and resistive microheaters integrated with inductive coils provide thermo-responsive drug delivery system for an antibacterial agent. In vivo evaluations demonstrate reliable, long-lived operation, and effective treatment for abdominal hernia defects, by clear evidence of suppressed complications such as adhesion formation and infections.

Micropatterned Elastomeric Composites for Encapsulation of Transient Electronics.

Although biodegradable, transient electronic devices must dissolve or decompose via environmental factors, an effective waterproofing or encapsulation system is essential for reliable, durable operation for a desired period of time. Existing protection approaches use multiple or alternate layers of electrically inactive organic/inorganic elements combined with polymers; however, their high mechanical stiffness is not suitable for soft, time-dynamic biological tissues/skins/organs. Here, we introduce a stretchable, bioresorbable encapsulant using nanoparticle-incorporated elastomeric composites with modifications of surface morphology. Nature-inspired micropatterns reduce the diffusion area for water molecules, and embedded nanoparticles impede water permeation, which synergistically enhances the water-barrier performance. Empirical and theoretical evaluations validate the encapsulation mechanisms under strains. Demonstration of a soft, degradable shield with an optical component under a biological solution highlights the potential applicability of the proposed encapsulation strategy.

Ultra-stretchable and biodegradable elastomers for soft, transient electronics.

As rubber-like elastomers have led to scientific breakthroughs in soft, stretchable characteristics-based wearable, implantable electronic devices or relevant research fields, developments of degradable elastomers with comparable mechanical properties could bring similar technological innovations in transient, bioresorbable electronics or expansion into unexplored areas. Here, we introduce ultra-stretchable, biodegradable elastomers capable of stretching up to ~1600% with outstanding properties in toughness, tear-tolerance, and storage stability, all of which are validated by comprehensive mechanical and biochemical studies. The facile formation of thin films enables the integration of almost any type of electronic device with tunable, suitable adhesive strengths. Conductive elastomers tolerant/sensitive to mechanical deformations highlight possibilities for versatile monitoring/sensing components, particularly the strain-tolerant composites retain high levels of conductivities even under tensile strains of ~550%. Demonstrations of soft electronic grippers and transient, suture-free cardiac jackets could be the cornerstone for sophisticated, multifunctional biodegradable electronics in the fields of soft robots and biomedical implants.

Wireless, Fully Implantable and Expandable Electronic System for Bidirectional Electrical Neuromodulation of the Urinary Bladder.

Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladder─the inability to release urine naturally─include the use of medications, voiding techniques, and intermittent catheterization, for which the patient inserts a tube directly into the urethra to eliminate urine. Although those are life-saving techniques, there are still unfavorable side effects, including urinary tract infection (UTI), urethritis, irritation, and discomfort. Here, we report a wireless, fully implantable, and expandable electronic complex that enables elaborate management of abnormal bladder function via seamless integrations with the urinary bladder. Such electronics can not only record multiple physiological parameters simultaneously but also provide direct electrical stimulation based on a feedback control system. Uniform distribution of multiple stimulation electrodes via mesh-type geometry realizes low-impedance characteristics, which improves voiding/urination efficiency at the desired times. In vivo evaluations using live, free-moving animal models demonstrate system-level functionality.

Zebra-inspired stretchable, biodegradable radiation modulator for all-day sustainable energy harvesters.

Recent advances in passive radiative cooling systems describe a variety of strategies to enhance cooling efficiency, while the integration of such technology with a bioinspired design using biodegradable materials can offer a research opportunity to generate energy in a sustainable manner, favorable for the temperature/climate system of the planet. Here, we introduce stretchable and ecoresorbable radiative cooling/heating systems engineered with zebra stripe-like patterns that enable the generation of a large in-plane temperature gradient for thermoelectric generation. A comprehensive study of materials with theoretical evaluations validates the ability to accomplish the target performances even under external mechanical strains, while all systems eventually disappear under physiological conditions. Use of the zebra print for selective radiative heating demonstrates an unexpected level of temperature difference compared to use of radiative cooling emitters alone, which enables producing energy through resorbable silicon-based thermoelectric devices. The overall result suggests the potential of scalable, ecofriendly renewable energy systems.

Factors associated with complications and conversion to laparotomy in women undergoing laparoscopically assisted vaginal hysterectomy.

OBJECTIVE: To identify risk factors for complications and conversion to laparotomy in women undergoing laparoscopically assisted vaginal hysterectomy (LAVH). DESIGN: Retrospective study. SETTING: Tertiary referral hospital. POPULATION: All 2012 consecutive women who underwent LAVH for non-malignant diseases in a single institution. METHODS: Retrospective study. MAIN OUTCOME MEASURES: Operative complications and conversion to laparotomy. RESULTS: Most of the LAVHs were successful, but conversion to laparotomy was required in 97 women (4.8%) because of pelvic adhesion (n= 71), large uterine size (n= 18) or bowel injury (n= 8). There were 45 women (2.2%) with complications (bladder injury, 26; bowel injury, 9; vascular injury, 9; and ureteral injury, 1). A history of previous cesarean section (twice or more) was a significant risk factor for complications [odds ratio (OR) 3.38]. A body mass index ≥30 kg/m(2) (OR 2.98), history of previous myomectomy (OR 6.19) and uterine weight ≥500 g (OR 3.24) independently influenced the risk of conversion to laparotomy. CONCLUSIONS: Risk factors identified in this study include a history of previous cesarean section (twice or more) and myomectomy, body mass index ≥30 kg/m(2) and uterine weight ≥500 g. The findings may be useful in counseling women preoperatively about the potential complications of LAVH.

A review of the technique and complications from 2,012 cases of laparoscopically assisted vaginal hysterectomy at a single institution.

AIMS: To present our experience of modified laparoscopically assisted vaginal hysterectomy (LAVH) and to evaluate the surgical outcomes and complications. METHODS: Women with benign gynaecologic tumours that underwent a modified LAVH at the Samsung Medical Centre were analysed retrospectively. The technique is primarily a vaginal hysterectomy with a minor component of the laparoscopic procedures (stage 2 laparoscopic hysterectomy (LH)) and had two modifications (vaginal anterior colpotomy and McCall culdoplasty) from the standard technique. RESULTS: A total of 2012 LAVH procedures were performed from January 2000 to May 2008. The mean duration of the operations and the uterine weight were 102±32 min and 305±168 g, respectively. In 196 (9.7%) cases, the uterine weight was more than 500 g. Conversion to laparotomy was needed in 97 cases. Major intraoperative complications occurred in 45 cases (2.2%): bladder injury, 26 (1.29%); bowel injury, nine (0.45%); haemorrhage of major vessels, nine (0.45%); and ureteral injury, one (0.05%). Major long-term complications occurred in three cases: one fistula and two trocar site herniations. CONCLUSIONS: Stage 2 LH combined with modified vaginal anterior colpotomy and modified McCall culdoplasty is safe and effective for benign gynaecologic tumours and the prevention of post-LAVH vaginal prolapse.

The use of misoprostol before hysteroscopic surgery in non-pregnant premenopausal women: a randomized comparison of sublingual, oral and vaginal administrations.

BACKGROUND: The aim of the present study was to evaluate the efficacy of misoprostol administered orally, vaginally, or sublingually on cervical ripening before hysteroscopic surgery in premenopausal non-pregnant women. METHODS: Non-pregnant premenopausal women scheduled for operative hysteroscopy (with a 10-mm hysteroscope) were assigned by computerized randomization to receive 400 mg of misoprostol, administered either orally or vaginally 6-8 h prior to surgery or 400 mg sublingually 2-4 h prior to surgery. The primary outcome in this study was the preoperative cervical width as measured by the largest number of Hegar dilators. The time to Hegar number 10 was also recorded along with side effects related to misoprostol and complications during surgery for each group. RESULTS: Patients were randomized to receive sublingual (n = 47), oral (n = 47) or vaginal (n = 47) misoprostol. The three groups were comparable in terms of age, BMI (body mass index), parity, gravidity, history of vaginal delivery, post-operative pathological findings and surgeon type. The preoperative cervical width [sublingual: 7.5 +/- 2.0 mm (8, 3-10); oral: 7.5 +/- 1.9 mm (7, 4-10); vaginal: 7.6 +/- 2.4 mm (8, 1-10)] was statistically similar among the groups. The time to Hegar number 10, side effects and complications during the hysteroscopy were comparable among the three groups. CONCLUSION: A limitation of this study was that the surgeons, but not the patients, were blinded to the test procedures. Nevertheless we found that sublingual, oral and vaginal misoprostol were equally effective for cervical priming before hysteroscopic surgery in premenopausal non-pregnant women.

Prognostic significance of p-STAT3 in patients with bulky cervical carcinoma undergoing neoadjuvant chemotherapy.

AIM: To better predict treatment responses for managing bulky cervical carcinoma with neoadjuvant chemotherapy (NAC). METHODS: The expression of p-STAT3 was analyzed by immunohistochemistry using paraffin-embedded pretreatment cervical biopsy tissues. The study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with NAC. RESULTS: Twenty (69.0%) of 29 patients were scored as p-STAT3-positive. Pathological response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%). The p-STAT3-positive patients had a longer disease-free survival compared to p-STAT3-negative patients (P = 0.03), though they had more frequent clinical nodal involvement (P = 0.046). CONCLUSION: Pretreatment assessment of p-STAT3 expression may provide additional information for the identification of patients with cervical cancer who have a favorable prognosis.

Single port access laparoscopic adnexal surgery.

STUDY OBJECTIVE: To estimate the feasibility, safety, and operative outcomes for the management of adnexal masses by single port access (SPA) laparoscopy with a wound retractor and a surgical glove. DESIGN: A prospective single-center study (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Twenty-four well selected patients with adnexal masses on imaging scans recruited from June 2008 through January 2009. INTERVENTIONS: Single port access laparoscopic adnexal surgery. MEASUREMENTS AND MAIN RESULTS: Single port access laparoscopic adnexal surgery was successfully completed in 22 of 24 patients. The median age of the patients was 45 years (range 23-63 years), and the median body mass index was 22 (range 18-29). The median tumor size was 5 cm (range 3-12 cm). The median operative time was 70 minutes (range 40-128 minutes). The estimated blood loss was minimal (range 10-100mL). The postoperative course was uneventful in all patients. The median postoperative hospital stay was 1 day (range 1-3 days). No postoperative complications were observed at follow-up. The 2 failed cases were as follow: 1 required an additional trocar for adequate adhesiolysis, and the other a staging laparotomy because of the finding of a borderline ovarian malignancy on frozen section pathologic study. CONCLUSION: The single port access laparoscopic adnexal surgery was safe and feasible and provided almost no visual scar.

Phase II study of combination chemotherapy with etoposide and ifosfamide in patients with heavily pretreated recurrent or persistent epithelial ovarian cancer.

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m(2)/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m(2)/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI > or =6 months had 50% of RR, while patients (n=31) with TFI <6 months had 12.9%. Median survival was 9 months at a median follow-up of 9.2 months. Grade 3 or 4 toxicities included neutropenia in 20.1% of the 139 cycles of ETI, anemia in 7.2% and thrombocytopenia in 8.6%. The ETI produces relatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC. This is significant in patients with TFI > or =6 months.

The prognostic significance of the SUVmax (maximum standardized uptake value for F-18 fluorodeoxyglucose) of the cervical tumor in PET imaging for early cervical cancer: preliminary results.

OBJECTIVE: The objective of this study was to evaluate the prognostic significance of the cervical tumor uptake of fluorine-18-labeled FDG (fluorodeoxyglucose) measured as the SUVmax (maximum standardized uptake value) by PET (Positron Emission Tomography) in patients with early cervical cancer treated with surgery+/-adjuvant therapy. METHODS: Forty-four patients (FIGO clinical stage IB to IIA) with biopsy-proven cervical cancer underwent PET before surgery. The SUVmax of the primary cervical tumor mass was obtained and compared with pathological prognostic factors after the initial treatment. In addition, we investigated the recurrence pattern according to the SUVmax and analyzed independent risk factors associated with the recurrence of disease. RESULTS: According to the tumor stage, the mean SUVmax significantly differed among groups (P=0.013). The SUVmax was significantly higher in patients with deep stromal invasion (>or=1 cm, P=0.0208), LVSI (lymph-vascular space invasion) (P=0.0429) and a pathologically confirmed large tumor size of more than 4 cm (P=0.0074) when compared to controls. Patients with a high SUVmax (>or=13.4) had a significantly reduced disease-free survival rate compared to patients with a low SUVmax (P=0.021). In addition, the SUVmax (>or=13.4) was a significant independent predictor of recurrence of cervical cancer after treatment with surgery (+/-adjuvant therapy) (P=0.0207). CONCLUSION: Patients with early cervical cancer showing a high SUVmax (>or=13.4) of the cervical tumor should be considered at increased risk for disease recurrence after surgery and may need more aggressive multimodal treatment.

Single-port access laparoscopic-assisted vaginal hysterectomy: a novel method with a wound retractor and a glove.

STUDY OBJECTIVE: To present our initial experience with single port-access laparoscopic-assisted vaginal hysterectomy (SPA-LAVH) by use of a wound retractor and a glove. DESIGN: Continuing, prospective study (Canadian Task Force classification II-3). SETTING: University teaching, research hospital, and a tertiary care center. PATIENTS: We performed the SPA-LAVH in 24 patients from May 6, 2008, through October 8, 2008. INTERVENTIONS: All cases of SPA-LAVH were performed by a single surgeon (T. J. K.). MEASUREMENTS AND MAIN RESULTS: We analyzed the data to determine the outcome of SPA-LAVH and compared the initial 10 cases (group A) and the latter 14 cases (group B) to consider the learning curve. Median and range are used to describe non-normal data. A total of 24 consecutive patients have undergone SPA-LAVH, for benign gynecologic conditions, including 16 uterine myomas and 8 cases of adenomyosis, regardless of body mass index or previous abdominal or pelvic surgery. All cases but 3 were performed exclusively through a single port. The median operative time, weight of the uterus, and estimated blood loss were 119 minutes (range 90 to 255 minutes), 347 g (range 225 to 732 g), and 400 mL (range 100 to 1000 mL), respectively. The decline in hemoglobin from before surgery to postoperative day 1 was from 0.7 to 4.3 g/dL, with a median of 2.05 g/dL. The median hospital stay (postoperative day) was 3 days (range 3 to 7). When we compared the operative outcomes between the 2 groups, there was a tendency toward a decreased operative time in group B, although the difference was not significant. However, there was a significant decrease in the estimated blood loss and hospital stay in group B (p = .00, = .04, respectively). CONCLUSION: The SPA-LAVH was safe and effective, and the procedure could be learned over a short period of time. Additional experience and continued investigation are warranted.

Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study.

OBJECTIVE: The aim of this trial was to investigate the efficacy and toxicity of a relative high-dose of topotecan combined with carboplatin in recurrent or persistent epithelial ovarian cancer (EOC). METHODS: Patients participating in this phase II trial received topotecan at a dose of 1.0 mg/m(2)/day intravenously (IV) on days 1 to 5 in combination with carboplatin AUC 5 IV on day 5, every 21 days. The primary outcome was response rate (RR) and the toxicity. The secondary measurements were duration of response, time to progression (TTP) and overall survival (OS). RESULTS: Fifty-nine patients entered the study and 53 were assessable for response. For this study, 260 courses of topotecan and carboplatin were given (median, 4 per patient; range, 1-8). The overall RR was 26.4%. The median duration of response and TTP were 7 and 6 months, respectively. The median OS was 19 months with a median follow-up period of 14 months. Initial platinum sensitivity and treatment free interval (TFI) >or=6 months were associated with RR and OS. In the platinum-sensitive group, RR and OS were 40.0% and 25 months, whereas in the platinum-resistant group, these were 8.7% and 11 months, respectively. Grade 4 neutropenia occurred in 40.7% of the patients, and grade 4 thrombocytopenia was seen in 32.2% with a bleeding event in two patients. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: The relative high-dose of topotecan combined with carboplatin was feasible and produced modest activity in recurrent or persistent EOC. The RR and survival data appear promising for the initially platinum-sensitive cohort and thus this regimen may be considered for further development in this patient.

Prognostic significance of VEGF expression in patients with bulky cervical carcinoma undergoing neoadjuvant chemotherapy.

BACKGROUND: The prediction of response to treatment would be valuable for managing cervical carcinoma with neoadjuvant chemotherapy. METHODS: To this end, the expression of VEGF was analyzed by immunohistochemistry using paraffin-embedded pre-treatment cervical biopsy tissues. This study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with neoadjuvant chemotherapy. RESULTS: Fifteen (51.7%) of 29 patients were scored as VEGF-positive. Response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%), and it was negatively associated with VEGF expression (P = 0.009). With logistic regression analysis, VEGF positivity continued to be an independent predictor for poor response (P = 0.032). In addition, the progression-free survival rate was significantly lower in patients with VEGF-positive tumors (P = 0.033). CONCLUSION: Pretreatment assessment of VEGF expression may provide additional information for identification of patients with cervical cancer who had a low likelihood of response to neoadjuvant chemotherapy and an unfavorable prognosis.

Outcome and reproductive function after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for patients with ovarian endodermal sinus tumor.

OBJECTIVE: The aim of this study was to investigate the outcome and reproductive function of patients with ovarian endodermal sinus tumor (EST) after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). METHODS: Between 1995 and 2006, 1034 patients with the diagnosis of ovarian cancer were treated at a single institution. Among these patients, 51 had a confirmed diagnosis of malignant ovarian germ cell tumor (MOGCT) including 20 cases of EST. We retrospectively reviewed those patients with EST, who received BEP as adjuvant chemotherapy. The doses were 15 mg/day of bleomycin on days 1 to 3, 100 mg/m(2)/day IV of etoposide on days 1 to 3 and 20 mg/m(2)/day of cisplatin on days 1 to 5. The median number of total cycles was six (range between three and nine). RESULTS: The median age of the patients with EST was 18 years (range 5 to 36). All except two were nulliparous. The overall survival rate was 90% at a median follow-up of 70 months. Two patients (10%) had disease recurrence in the pelvis. Of the 15 patients who were treated with fertility-sparing surgery, all had regular menstruation following the completion of adjuvant chemotherapy, and two of these patients had pregnancies with live birth deliveries and no complications. CONCLUSION: In patients with EST, the cumulative high-dose BEP regimen resulted in excellent overall survival and did not seem to impair ovarian function.

Prognostic value of baseline lymphocyte count in cervical carcinoma treated with concurrent chemoradiation.

PURPOSE: This study examined factors predicting tumor response and progression-free survival in patients with locally advanced cervical carcinoma treated with concurrent chemoradiation (CCRT). METHODS AND MATERIALS: Medical records of 143 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics Stage IB2 to IVA) treated with CCRT were reviewed. Univariate and multivariate analyses were used to retrospectively evaluate prognostic factors, including baseline lymphocyte count, that affect tumor response and progression-free survival. RESULTS: Of the variables evaluated, greater baseline lymphocyte count was the factor most predictive of a complete clinical response, followed by smaller tumor size (p = 0.003 and p = 0.007, respectively). Multivariate analysis showed baseline lymphocyte count, which was treated as a continuous variable with every 1 x 10(9) lymphocytes/L, to remain a prognostic factor with an odds ratio of 3.08 (95% confidence interval, 1.31-7.23). In addition, a statistically significant association (p = 0.023) was found between baseline lymphocyte count and progression-free survival, with a hazard ratio of 0.42 (95% confidence interval, 0.20-0.89) in the Cox proportional hazards model. CONCLUSIONS: Despite the small number of patients and possible biologic variation existing in lymphocyte subset number and activity, these findings highlight the strong prognostic value of baseline lymphocyte count in patients with locally advanced cervical carcinoma treated with CCRT. Therefore, a larger number of patients and analysis of lymphocyte subsets are needed.