The Dynamics of Aerotaxis in a Simple Eukaryotic Model.

In aerobic organisms, oxygen is essential for efficient energy production, and it acts as the last acceptor of the mitochondrial electron transport chain and as regulator of gene expression. However, excessive oxygen can lead to production of deleterious reactive oxygen species. Therefore, the directed migration of single cells or cell clumps from hypoxic areas toward a region of optimal oxygen concentration, named aerotaxis, can be considered an adaptive mechanism that plays a major role in biological and pathological processes. One relevant example is the development of O2 gradients when tumors grow beyond their vascular supply, leading frequently to metastasis. In higher eukaryotic organisms, aerotaxis has only recently begun to be explored, but genetically amenable model organisms suitable to dissect this process remain an unmet need. In this regard, we sought to assess whether Dictyostelium cells, which are an established model for chemotaxis and other motility processes, could sense oxygen gradients and move directionally in their response. By assessing different physical parameters, our findings indicate that both growing and starving Dictyostelium cells under hypoxic conditions migrate directionally toward regions of higher O2 concentration. This migration is characterized by a specific pattern of cell arrangement. A thickened circular front of high cell density (corona) forms in the cell cluster and persistently moves following the oxygen gradient. Cells in the colony center, where hypoxia is more severe, are less motile and display a rounded shape. Aggregation-competent cells forming streams by chemotaxis, when confined under hypoxic conditions, undergo stream or aggregate fragmentation, giving rise to multiple small loose aggregates that coordinately move toward regions of higher O2 concentration. By testing a panel of mutants defective in chemotactic signaling, and a catalase-deficient strain, we found that the latter and the pkbR1 null exhibited altered migration patterns. Our results suggest that in Dictyostelium, like in mammalian cells, an intracellular accumulation of hydrogen peroxide favors the migration toward optimal oxygen concentration. Furthermore, differently from chemotaxis, this oxygen-driven migration is a G protein-independent process.

Long-Term Oncologic Outcomes of Minimally Invasive Proctectomy for Rectal Adenocarcinoma.

BACKGROUND: Long-term oncologic outcomes after minimally invasive surgery (MIS) for rectal adenocarcinoma compared to open surgery continue to be debated. We aimed to review our high-volume single-institution outcomes in MIS rectal cancer surgery. METHODS: A retrospective review of a prospectively collected database was completed of all consecutive adult patients with rectal adenocarcinoma treated from January 2005 through December 2011. Stage IV or recurrent disease was excluded. Demographics and operative and pathologic details were reviewed and reported. Primary endpoints include survival and recurrence. RESULTS: A total of 324 patients were included and median follow-up was 54 months (IQR = 37.0, 78.8). The mean age was 58.2 ± 14.1 years. Tumors were in the upper rectum in 111 patients, mid-rectum in 113 patients, and lower rectum in 100 patients. Stage III disease was most common (49.4%). Overall conversion to open procedure rate was 13.9%. The circumferential radial margin was positive in only 1 patient (0.3%) and the mean lymph node yield was 24.7 ± 17.2. Cancer recurred in 42 patients (13%), 10 (2.5%) patients developed local recurrence, 32 (9.8%) developed distant metastasis, and 2 (0.6%) patients had both. The 5-year overall survival for stage 0, 1, 2, and 3 disease is 96, 91, 80, and 77%, respectively (p = 0.015). CONCLUSION: In carefully selected rectal cancer patients treated with MIS, long-term outcomes of survival and recurrence appear to compare favorably to previously published series.

Timing of Surgical Resection for Curative Colorectal Cancer with Liver Metastasis.

PURPOSE AND DESIGN: Optimal surgical strategy for resectable synchronous colorectal cancer with liver metastasis (SCRLM) remains a therapeutic dilemma. Multiple retrospective studies including several meta-analyses have been published since 2001 to help facilitate the decision making process and identify the optimal surgical approach. Controversy limits the generalization of available data to draw conclusions. A review of available literature on appropriate surgical timing may alleviate confusion among physicians and promote a more evidence based approach. RESULTS AND CONCLUSION: Current evidence supports the feasibility, safety, and equivalent oncological outcomes of simultaneous curative resection of stage IV colorectal cancer with liver metastasis in appropriately selected patients.

Safety of an Enhanced Recovery Pathway for Patients Undergoing Open Hepatic Resection.

BACKGROUND: Enhanced recovery pathways (ERP) have not been widely implemented for hepatic surgery. The aim of this study was to evaluate the safety of an ERP for patients undergoing open hepatic resection. METHODS: A single-surgeon, retrospective observational cohort study was performed comparing the clinical outcomes of patients undergoing open hepatic resection treated before and after implementation of an ERP. Morbidity, mortality, and length of hospital stay (LOS) were compared between pre-ERP and ERP groups. RESULTS: 126 patients (pre-ERP n = 73, ERP n = 53) were identified for the study. Patient characteristics and operative details were similar between groups. Overall complication rate was similar between pre-ERP and ERP groups (37% vs. 28%, p = 0.343). Before and after pathway implementation, the median LOS was similar, 5 (IQR 4-7) vs. 5 (IQR 4-6) days, p = 0.708. After adjusting for age, type of liver resection, and ASA, the ERP group had no increased risk of major complication (OR 0.38, 95% CI 0.14-1.02, p = 0.055) or LOS greater than 5 days (OR 1.21, 95% CI 0.56-2.62, p = 0.627). CONCLUSIONS: Routine use of a multimodal ERP is safe and is not associated with increased postoperative morbidity after open hepatic resection.

Annual Surgeon Volume and Patient Outcomes Following Laparoscopic Totally Extraperitoneal Inguinal Hernia Repairs.

PURPOSE: Data on laparoscopic totally extraperitoneal inguinal hernia repairs (TEP-IHRs) suggest that approximately 250 operations are needed to gain mastery, but the annual volume required to maintain high-quality outcomes is unknown. MATERIALS AND METHODS: A retrospective review was performed of every patient undergoing a TEP-IHR at the Mayo Clinic (Rochester, MN) from 1995 to 2011. Analysis focused on the annual volume of 21 staff surgeons and their specific patient outcomes broken up into three groups: Group 1 (G1) (n = 1 surgeon) performed >30 repairs per year; Group 2 (G2) (n = 3 surgeons), 15-30 repairs; and Group 3 (G3) (n = 17), <15 repairs. RESULTS: In total, 1601 patients underwent 2410 TEP-IHRs, with no significant patient demographic differences among groups. Greater annual surgeon volume (G1 > G2 > G3) was associated with improved outcomes as shown by the respective rates for intra- (1%, 2.6%, and 5.6%) and postoperative (13%, 27%, and 36%) complications, need for overnight stay (17%, 23%, and 29%), and hernia recurrence (1%, 4%, and 4.3%) (all P < .05). Surgeons with greater annual operative volumes were more likely to operate on patients with bilateral and recurrent hernias. Surgeons performing at least 15 repairs per year (G1 and G2) showed improvements in quality metrics over time. CONCLUSIONS: Annual operative volumes of >30 repairs per year are associated with the highest quality outcomes for TEP-IHR. Operative volumes of at least 15 repairs per year are associated with improvements in quality metrics over time. Mentorship and operative assistance of low-volume TEP-IHR surgeons may be useful in improving patient outcomes.

Optimizing training cost-effectiveness of simulation-based laparoscopic inguinal hernia repairs.

BACKGROUND: Motor learning theory suggests that highly complex tasks are probably best trained under conditions of part task (PT), as opposed to whole-task (WT) training. Within PT, random practice of tasks has been shown to lead to improved skill retention and transfer. METHODS: General surgery residents were equally randomized to PT vs WT, mastery learning type, and simulation-based training of laparoscopic inguinal hernia repair. Training time and resources used to reach mastery (skill acquisition), performance at 1-month testing (skill retention), and intraoperative time and performance scores (skill transfer) were compared. RESULTS: Forty-four general surgery trainees were randomized. All residents achieved mastery benchmarks. Trainees in the PT group achieved mastery on average 17 minutes faster (60.2 ± 23.8 vs 77.1 ± 24.8 minutes, P = .02, saving 6.2 instructor hours), used fewer material resources (curricular cost savings of $2,380 or $121 per learner), and were more likely to retain mastery level performance at 1-month retention testing (59% vs 22.7% P = .03). No differences in intraoperative performance were encountered. CONCLUSIONS: For laparoscopic inguinal hernia repair, random PT simulation-based training seems to be more cost-effective, compared with WT training.

Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience.

BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings. METHODS: A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan-Meier estimates and log-rank tests. RESULTS: A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m(2) (range: 17-46 kg/m(2) ). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001). CONCLUSIONS: The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.

The rationale for combining an online audiovisual curriculum with simulation to better educate general surgery trainees.

BACKGROUND: Surgery interns' training has historically been weighted toward patient care, operative observation, and sleeping when possible. With more protected free time and less clinical time, real educational hours for trainees in 2013 are precious. METHODS: We created a 20-session (3 hours each) simulation curriculum (with pre- and post-tests) and a 24/7 online audiovisual (AV) curriculum for surgery interns. Friday morning simulation sessions emphasize operative skills and judgment. AV clips (using operating room, whiteboard, and simulation center videos) take learners through 20 different general surgery operations with follow-up quizzes. We report our early experience with this novel setup. RESULTS: Thirty-two surgical interns (2012-2013) attended simulation sessions on 20 separate subjects (hernia, breast, hepatobiliary, endocrine, etc). Post-test scores improved (P < .05) and trainees enjoyed using surgical skills for 3 hours each Friday morning (mean, >4.5; Likert scale, 1-5). The AV curriculum feedback is similar (mean, >4.3) and usage is available 24/7 preparing learners for both operating room and simulation sessions. Most simulation sessions utilize low-fidelity models to keep costs <$50 per session. Scores on our semiannual Surgical Olympics (mean score of 49.6 in July vs 82.9 in January; P < .05) improved significantly, suggesting that interns are improving their surgical skills and knowledge. CONCLUSION: Residents enjoy and learn from the step-by-step, in-house, AV curriculum and both appreciate and thrive on the 'hands-on' simulation sessions mimicking operations they see in real operating rooms. The cost of these programs is not prohibitive and the programs offer simulated repetitions for duty-hour-regulated trainees.

Predictors of chronic groin discomfort after laparoscopic totally extraperitoneal inguinal hernia repair.

BACKGROUND: Chronic groin discomfort is an undesired complication of laparoscopic totally extraperitoneal (TEP) inguinal hernia repairs. We examined whether perioperative factors may be associated with an increased risk of developing this problem and if their recognition could lead to preventive strategies. STUDY DESIGN: We performed a retrospective review of 1 surgeon's experience with 1,479 TEP repairs on 976 patients from 1995 to 2009. A mailed survey, which included a groin discomfort questionnaire (Carolinas Comfort Scale), was distributed to all patients. Symptom severity grading (range 0, none to 5, severe) was used to sort individual responses. Perioperative factors were compared between asymptomatic and symptomatic patients with varying levels of discomfort. RESULTS: There were 691 patients (71%) who provided complete responses to the questionnaire. Median follow-up was 5.7 years (range 0 to 14.4 years). The majority (n = 543, 79%) denied any symptoms of mesh sensation, pain, or movement limitation. In the remaining 148 (21%) patients, symptoms were most often mild (n = 108), followed by mild but bothersome (n = 25), and 15 patients (2%) had moderate or severe symptoms. Symptomatic patients were younger (median age 52 vs 57 years, p = 0.002) and were more likely to have had the TEP repair for recurrent hernias (24% vs 17%, p = 0.035). Operative diagnosis, bilateral exploration, mesh fixation techniques, perioperative complications, American Society of Anesthesiologists grade, and length of hospital stay were not associated with chronic groin discomfort. CONCLUSIONS: The majority of patients are asymptomatic after a laparoscopic TEP inguinal hernia repair. Most of the symptomatic patients do not have any bothersome symptoms. Given that younger age and a repair for recurrent hernia were predictors of chronic groin discomfort, we counsel these patients about their increased risks.

Incidence of inguinal hernia repairs in Olmsted County, MN: a population-based study.

OBJECTIVE: To determine age- and sex-specific incidence rates of inguinal hernia repairs (IHR) in a well-defined US population and examine trends over time. BACKGROUND DATA: IHR represent a substantial burden to the US healthcare system. An up-to-date appraisal will identify future healthcare needs. METHODS: A retrospective review of all IHR performed on adult residents of Olmsted County, MN, from 1989 to 2008 was performed. Cases were ascertained through the Rochester Epidemiology Project, a record linkage system with more than 97% population coverage. Incidence rates were calculated by using incident cases as the numerator and population counts from the census as the denominator. Trends over time were evaluated using Poisson regression. RESULTS: During the study period, a total of 4026 IHR were performed on 3599 unique adults. Incidence rates per 100,000 person-years were greater for men: 368 versus 44 for women, and increased with age: from 194 to 648 in men, and from 28 to 108 in women between 30 and 70 years of age. Initial, unilateral IHR comprised 74% of all IHR types. The lifelong cumulative incidence of an initial, unilateral or a bilateral IHR in adulthood was 42.5% in men and 5.8% in women. Over time (from 1989 to 2008), the incidence of initial, unilateral IHR in men decreased from 474 to 373 (relative reduction, RR = 21%). Bilateral IHR increased from 42 to 71 (relative increase = 70%), contralateral metachronous IHR decreased from 29 to 11 (RR = 62%), and recurrent IHR decreased from 66 to 26 (RR = 61%); for all changes P < 0.001. CONCLUSIONS: IHR are common, their incidence varies greatly by age and sex and has decreased substantially over time in Olmsted County, MN.

Role of major vascular resection in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Historically, direct vascular extension of intrahepatic cholangiocarcinoma (ICC) has often been considered a contraindication to resection. However, recent studies have suggested safety and efficacy of hepatectomy with major vascular resection in this patient population. The aim of this study was to investigate the short and long-term clinical outcomes of patients with ICC treated with hepatectomy with or without major vascular resection. METHODS: This retrospective cohort study included all patients with ICC who underwent major liver resection between 1997 and 2011. Clinical outcomes were compared between patients treated with major hepatectomy and vascular resection (VR) and those without vascular resection (NVR). Kaplan-Meier survival estimates were used to compare overall survival (OS) between patients in VR and NVR groups. RESULTS: A total of 121 patients (median age 60; 42 % male) underwent major hepatectomy for ICC. Major vascular resection was performed in 14 (12 %) patients (IVC = 9, PV = 5). Age, sex, American Society of Anesthesiology (ASA) class, tumor size, lymph node status, and CA-19 9 were comparable (all p ≥ 0.184) between VR and NVR groups. Major postoperative complications (Dindo-Clavien ≥3) occurred in four (29 %) patients in the VR group and 17 (16 %) in the NVR group (p = 0.263). Postoperative death occurred in one patient in the VR group due to liver failure. Median OS did not differ between patients treated with and without vascular resection (32 vs. 49 months, respectively, p = 0.268). CONCLUSIONS: Hepatectomy combined with IVC or PV resection can be safely performed in patients with ICC. Major vascular resection does not affect short and long-term outcomes in this patient population.

Impact of resident participation on laparoscopic inguinal hernia repairs: are residents slowing us down?

OBJECTIVE: The time it takes to complete an operation is important. Operating room (OR) time is costly and directly associated with infectious complications and length of stay. Intuitively, procedures take longer when a surgical resident is operating. How much extra time should we take to train residents? We examined the relationship between laparoscopic inguinal hernia repair (IHR) procedure duration and resident participation and its impact on the development of complications and hospital stay. METHODS: Data from patients undergoing laparoscopic IHR in participating institutions of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2007 to 2009 were retrospectively reviewed. Patients with current procedural terminology (CPT) codes 49650 and 49651 (laparoscopic initial and recurrent IHR) comprised our patient cohort. Participation of staff surgeon and resident postgraduate year level (PGY) were used as the main predictors for operative outcomes. RESULTS: A total of 6223 patients underwent laparoscopic IHR as their main procedure with no additional or concurrent procedures; 92% were men, 21% of the repairs were bilateral. In total, there were 98 patients with at least 1 complication (1.6%). Resident involvement was present in 3565 cases (57%) broken down by PGY1: 12%, PGY2: 12%, PGY3: 21%, PGY4: 19%, PGY5 or above: 36%. Median operative time was 45 minutes for staff surgeons alone and 64 minutes when there was a resident present (p < 0.001). PGY level predicted operative duration: higher PGY levels correlated with greater operative times (PGY1 median time 58 min vs PGY ≥ 5 = 67 min, p < 0.001). Resident participation was not a significant predictor for the development of complications (p = 0.30). CONCLUSIONS: Laparoscopic IHR is performed faster by staff surgeons without residents. There was no difference in the complication rate when residents were involved. Teaching and mentoring residents in the OR for laparoscopic IHR is safe and laudable.

Lessons learned from an unusual case of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated with poor long-term outcomes despite aggressive surgical and chemotherapeutic interventions. We recently treated a 56-year-old woman with right-sided IBC and biopsy-proven cutaneous metastases to her back and left breast. She underwent chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One year after diagnosis, she is currently disease-free based on positron-emission tomography (PET) imaging and repeat skin biopsies. To provide insight into the management of IBC, we present this interesting case with a reflection on important lessons to be learned.

Trends in the utilization of inguinal hernia repair techniques: a population-based study.

BACKGROUND: The use of inguinal hernia repair techniques in the community setting is poorly understood. METHODS: A retrospective review of all inguinal hernia repairs performed on adult residents of Olmsted County, MN, from 1989 to 2008 was performed through the Rochester Epidemiology Project. RESULTS: A total of 4,433 inguinal hernia repairs among 3,489 individuals were reviewed. Non-mesh-based repairs predominated in the late 1980s (94% in 1989), declined throughout the 1990s (40% in 1996), and are rarely used nowadays (4% in 2008). Open mesh-based repairs comprised 21% in 1990, peaked in 2001 with 72%, and declined to 55% in 2008. The adoption of laparoscopic repairs began in 1992 (6%) and has increased steadily to 41% in 2008 (P < .001). CONCLUSIONS: Although non-mesh-based repairs, once the predominant method, have been supplanted by open mesh-based techniques, nowadays the use of laparoscopic inguinal hernia repair techniques has increased substantially to nearly equal that of open mesh-based techniques.

Handing over patient care: is it just the old broken telephone game?

BACKGROUND: Handing over patient care remains a poorly understood process and remains a leading cause of medical error. We sought to examine how hand off delivery methods affect hand off quality and whether improvement would occur over time without formal training. DESIGN: Three simulated-patient hand offs were developed; each with a distinct delivery method: in-person (IP), video-based (VB), and screen-based (SB). Participants were evaluated up to 4 times, each 6 months apart. During evaluations, residents received the 3 hand offs, answered a sleep and preference questionnaire, and proceeded to hand off the same 3 patients. Sessions were video-reviewed and hand offs scored for quality measures: word accuracy, errors of omission or commission, and appropriateness of clinical judgment. Quality measures among delivery methods and changes over time were compared. RESULTS: Sixty-eight General Surgery residents (postgraduate year [PGY] 1-2) participated in at least 2 testing sessions, with 13 participating in 4. The IP method was superior to VB and SB for most hand off quality measures (each p < 0.001). With repeated testing, hand off quality measures improved (p < 0.001). However, patient hand offs continued to remain non-optimal, with appropriate judgment present in only 47%-77% of the hand offs. Sleep hours (mean 5 ± 2) were not found to be associated with hand off quality measures (p > 0.05). Most trainees preferred the IP method (73% vs 5% VB, 15% SB, 7% other; p < 0.001). CONCLUSIONS: There is a need to provide formal training in hand off quality early in residency training. General surgery trainees clearly prefer and performed better, though not perfect, hand offs with the in-person method.

Influence of the secondary deployment of expanded polytetrafluoroethylene-covered stent grafts on maintenance of transjugular intrahepatic portosystemic shunt patency.

PURPOSE: To evaluate the effects of secondary deployment of expanded polytetrafluoroethylene (ePTFE)-covered stent grafts in the treatment of dysfunctional transjugular intrahepatic portosystemic shunts (TIPSs) in comparison with other common approaches (conventional angioplasty or implantation of bare metal stents). MATERIALS AND METHODS: A retrospective review of 121 dysfunctional bare metal TIPS presenting between 2000 and 2004 was conducted. The group was divided into four subgroups according to the type of intervention: conventional angioplasty (52 cases; 43%), bare metal stent deployment (35 cases; 28.9%), nondedicated ePTFE-covered stent-graft deployment (15 cases; 12.4%), and dedicated ePTFE-covered stent-graft deployment (19 cases; 15.7%). In all four groups, the primary patency after the specific intervention was calculated and mutually compared. RESULTS: Primary patency rates after 12 and 24 months were 49.7% and 25.3%, respectively, in conventional angioplasty; 74.9% and 64.9%, respectively, with bare metal stents; 75.2% and 64.5%, respectively, with nondedicated ePTFE-covered stent grafts; and 88.1% and 80.8%, respectively, with dedicated ePTFE-covered stent grafts. CONCLUSIONS: In the treatment of dysfunctional TIPS, better patency after the intervention was obtained by deploying dedicated ePTFE-covered stent grafts in comparison with conventional angioplasty, bare metal stents, and nondedicated ePTFE-covered stents.