Mitf Links Neuronal Activity and Long-Term Homeostatic Intrinsic Plasticity

Publisher's versionNeuroplasticity forms the basis for neuronal circuit complexity and differences between otherwise similar circuits. We show that the microphthalmia-associated transcription factor (Mitf) plays a central role in intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable, have a reduced A-type potassium current (IA) and exhibit reduced expression of Kcnd3, which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the IA. Furthermore, expression of the Mitf and Kcnd3 genes is activity dependent in OB projection neurons and the MITF protein activates expression from Kcnd3 regulatory elements. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habituation for an odorant following long-term exposure, indicating that regulation of Kcnd3 is pivotal for long-term olfactory adaptation. Our findings show that Mitf acts as a direct regulator of intrinsic homeostatic feedback and links neuronal activity, transcriptional changes and neuronal function.This work was supported by the Icelandic Research Fund, Rannís Grants 152715-053 and 163068-051Peer reviewe

Robot-assisted laparoscopic surgery for cervical cancer

Cervical cancer is the third most common cancer in women worldwide and the fourth leading cause of cancer death. In Western countries, it is the 10th most common cause of cancer death. Cervical cancer often affects young women ( 1 year) morbidity. There was a steep learning curve for the surgical time, and the adverse events, even though usually mild, decreased with time. There was a relatively high incidence of vaginal dehiscence (6%). The robot has aided the introduction of laparoscopic RH at our center and is a feasible option for the patients. Study II: Do surgical knots tied with the robot have equal tensile strength as knots tied by hand? Four knot formations were tied by four surgeons in the robot and compared with the hand-tied knot recommended by the manufacturer of the thread. One out of four surgeons tied the knots in the robot with equal strength to the hand- tied knots. Strand-to-strand knots performed better than loop-to-strand knot and should therefore be recommended. Study III: Is it possible to perform laparoscopic transabdominal radical trachelectomy aided by the robot with consistent surgical precision? Two quality parameters (cervical length and placement of cerclage) were compared in 12 women operated with the robot with 10 women operated vaginally. The two groups had the same remaining cervical length, but the placement of the cerclage was more precise and consistent in the robot group. Study IV: Is it possible to perform robot-assisted RH with the same hospital cost as with laparotomy? Fifty-one patients operated with open RH were compared with 180 patients operated with robot assistance. The robot was more expensive in the beginning, but after 90 operations (3 years), there was no difference in hospital cost. Study V: Is it oncologically safe to operate women with early cervical cancer with the robot? The oncological outcome for 170 women operated with the robot was compared with FIGO results. This comparison does not raise concerns about oncological outcome following robot-assisted RH for cervical cancer

Hospital costs for robot-assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy.

OBJECTIVE: To compare robot-assisted laparoscopy and laparotomy for radical hysterectomy and pelvic lymphadenectomy in terms of hospital costs. METHODS: Consecutive women undergoing radical hysterectomy and pelvic lymphadenectomy as a sole procedure between January 2001 and February 2012 were included. We compared OR times, hospital stay, procedure specific costs, blood transfusions and cost for readmissions and re-interventions until three months after surgery for 231 women operated who received either an open (n=51) or a robot-assisted laparoscopic radical hysterectomy (n=180). The hospital internal charges and purchase costs were used for estimation. The specific robotic cost was based on an investment depreciation time of seven years, with 400 operations performed annually, costs for maintenance, robotic instruments, robot-specific assistant's instruments and robot draping. RESULTS: The estimated mean costs for an open radical hysterectomy was $12,986, for the first 30 robotic radical hysterectomies was$18,382, and for the last 30 was $12,759, with a break even in cost after 90 robotic procedures. The specific robot costs ($3469) was, for the last robot cohort, compensated mainly by an average of 22min shorter OR time and 4.9days shorter hospital stay. CONCLUSION: Given 400 robot operations annually, and only after a substantial implementation period, it is feasible to perform robot-assisted radical hysterectomy at an equal hospital cost compared with open surgery

Long term recurrence and survival following robotic radical hysterectomy for early stage cervical cancer.

Objective: To evaluate long-term oncological outcome and surgical quality of robotic radical hysterectomy for cervical cancer. Methods: Consecutive women with stage IA2 to IIA operated between March 2006 and May 2012 with a robotic radical hysterectomy and pelvic lymphadenectomy were prospectively followed up until five years after surgery or until death. Details regarding clinical results, recurrence and death from disease were analysed and compared with FIGO survival data and EORTC-GCG quality parameters. Results: Of 170 included women; two were lost to follow up leaving 168 for analysis (16% stage IA2, 73% stage IB1 and 11% stage ≥ IB2). 22% had positive lymph nodes and 40% received postoperative chemoradiation. Median follow up was 46.5 months (range 6-91 months). A total of 21 women (12%) recurred of which nine women (5%) had a locoregional pelvic recurrence and 12 women had (7%) had a distant recurrence. Three and five year recurrence free survival was 93% and 89% respectively and over all survival was 96% and 93% respectively. Port site recurrences occurred in two patients, one having a node positive stage IB1 neuroendocrine cancer, and the other having a stageIB2 mucinous adenocarcinoma with multiple nodal metastases and micro-metastases on both adnexa. Both of them have died in their disease. No other recurrences possibly associated with the surgical technique per se occurred. Conclusion: Survival and recurrence data are comparable with FIGO reports and quality levels suggested by the EORTC-GCG. The EORTC-GCG surgical / clinical quality parameters were met for 16 of 19 criteria. The overall results do not raise concerns regarding the oncological outcome following robot-assisted surgery for early cervical cancer. The port site recurrences may be related to the tumour biology of the high-risk histologies, the surgical technique per se or a combination of those

A randomized trial comparing vaginal- and laparoscopic hysterectomy to robot-assisted hysterectomy.

To investigate the hospital cost and short-term clinical outcome of traditional minimally invasive versus robot-assisted hysterectomy in women primarily considered unavailable for vaginal surgery

The effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease.

The study objective was to assess the effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease. This is a retrospective cohort study. It is a Canadian Task Force classification II-2 study conducted at the University Hospital, Sweden. The patients were 949 women planned for robotic hysterectomy for malignant (75 %) and benign (25 %) gynecological disease between October 2005 and December 2013. They were continuously evaluated for the rate of intraoperative and postoperative complications up to 1-year post-surgery, the latter according to Clavien-Dindo classification following the introduction of robotic surgery with special awareness of complications possibly related to robot-specific risk factors, the description of refinement of practice and assessment of the effect of these measures. The rate of intraoperative complications, the overall rate of complications and the rate of ≥grade 3 complications decreased from the first to the last time period (4.8 vs 2.6 %, p = 0.037, 34 vs 19 %, p = 0.003 and 13.5 vs 3.2 %, p = 0.0003, respectively). The rate of intraoperative complications and the rate of postoperative complications possibly related to robot-specific risk factors was reduced from the first to the last time period (3.8 vs 0.6 %, p = 0.028 and 7.7 vs 1.5 %, p = 0.003, respectively). In patients undergoing robotic hysterectomy for malignant and benign gynecological disease intraoperative and postoperative complications and complications possibly related to the robotic approach diminish with training, experience and refinement of practice

Histopathology indicates lymphatic spread of a pelvic retroperitoneal ectopic pregnancy removed by robot-assisted laparoscopy with temporary occlusion of the blood supply.

Abstract Retroperitoneal ectopic pregnancies are extremely rare and a diagnostic and therapeutic challenge as an early diagnosis is difficult and all treatments entail a risk for severe bleeding. We present a case of a live completely retroperitoneal ectopic pregnancy in the right obturator fossa. Following 3D color Doppler vaginal ultrasonography to evaluate the relation to larger blood vessels the pregnancy was completely removed by robot-assisted laparoscopic surgery. The hypogastric artery was temporarily occluded by removable vessel clips. Time for surgery was 126 minutes, no bleeding occurred. The postoperative course was uneventful and s-betahCG normalized in five weeks. Histopathology of the intact specimen showed trophoblast surrounded by lymphatic tissue. We believe robot-assisted laparoscopic surgery is a feasible and safe technique for surgery of retroperitoneal ectopic pregnancies with similar or other locations allowing occlusion of the main supplying artery. Lymphatic spread may explain retroperitoneal ectopic pregnancies

Quality of life and long-term clinical outcome following robot-assisted radical trachelectomy

Quality of Life and long-term clinical outcome following robot-assisted radical trachelectomy. Objectives: To evaluate quality of life (QoL) and long-term clinical outcome following robot-assisted radical trachelectomy (RRT). Study Design: Prospectively retrieved clinical data were rereviewed on all women planned for a fertility sparing RRT for early stage cervical cancer at Skåne University Hospital, Sweden between 2007 and 2020. QoL was assessed using the validated questionnaires EORTC QLQ-C30, QLQ-CX24 and the Swedish LYMQOL. Results: Data was analyzed from 49 women, 42 with a finalised RRT and seven with an aborted RRT due to nodal metastases (n = 3) or insufficient margins (n = 4). At a median follow-up time of 54 months one recurrence (2%) occurred (aborted RRT). According to QLQ-C30 the median global health status score was 75. The disease specific QLQ-C24 showed an impact on symptoms related to sexual function where sexual/vaginal functioning had a median score of 25 and 48% of patients reported worry that sex would cause physical pain. Despite this the functional items sexual activity and sexual enjoyment both had a median score of 66.7. Lymphoedema was reported in 45%, where 9% reported severe symptom with an impact on their QoL. No intraoperative complications and no postoperative complications ≥ Clavien Dindo grade III were observed. Twenty-two of 28 (79%) women who attempted to conceive were successful. A metronidazole/no intercourse regimen was applied between GW 15 + 0–21 + 6 in 26 of 28 pregnancies beyond first trimester resulting in a 92% term (≥GW 36 + 0) delivery rate. Conclusions: Although robot-assisted radical trachelectomy in this cohort was associated with a low recurrence rate, a high fertility rate and an exceptionally high term delivery rate, women's quality of life was affected postoperatively, particularly with regards to their sexual well-being and lymphatic side-effects

Robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy with short and long term morbidity data.

OBJECTIVE: To evaluate feasibility and morbidity of robot assisted laparoscopic radical hysterectomy. METHODS: From December 2005 to September 2008 robot assisted laparoscopic radical hysterectomy and pelvic lymphadenectomy was performed on 80 women. Using a prospective protocol, and an active investigation policy for defined adverse events, perioperative, short and long term data were obtained. RESULTS: Time for surgery (skin to skin) reached 176 and 132 min after 9 and 34 procedures respectively. All tumours were radically removed. Median number of retrieved lymph nodes was 26 (range 15-55). All women had an early follow up (1-3 months) and 43 of eligible 46 women (93%) had a long term follow up (>/=12 months). In 33 of 80 women (41%) the peri/postoperative period was uneventful. The remainder had one or more mainly mild adverse events, most commonly from the vaginal cuff (n=17, 21%) or the lymphatic system (n=16, 20%). The proportion of uneventful cases increased significantly over time. Five women were resutured for dehiscence of the vaginal cuff, two women were reoperated for trocar site hernias and one woman had a ureter stricture that resolved following stent treatment. Eight women (14%) needed 60 days or more to resume spontaneous voiding. One 72-year old woman with disseminated endometrial cancer on autopsy died of pulmonary embolism 31 days after surgery. CONCLUSIONS: Robot assisted laparoscopic radical hysterectomy is a feasible alternative to conventional laparoscopy and open surgery. Effort should be made to ensure proper closure of the vaginal cuff, trocar sites and to develop nerve sparing techniques