Cost-effectiveness analysis of universal germline testing for patients with pancreatic cancer.

BACKGROUND: Historically, germline testing of patients with pancreatic cancer was performed selectively in patients with a strong family history of cancer. Current guidelines recommend universal testing because some patients may have actionable germline pathogenic variants without family history. METHODS: We conducted a cost-effectiveness analysis using a decision-tree model to compare universal versus selective testing strategies for patients with pancreatic cancer. Costs, probabilities, and overall survival were estimated from the published literature and institutional data. One-way and probabilistic sensitivity analyses explored model uncertainty. RESULTS: Universal germline genetic testing had an incremental cost of $310 with an increase of 0.003 life-years. The incremental cost-effectiveness ratio was $121,924/life-years. Parameters which were most impactful (sensitivity analysis) included the median overall survival of patients with advanced disease treated with personalized therapy, cost of personalized therapy for advanced disease, and the probability of receiving personalized therapy in advanced disease. A strategy of selective testing was more cost-effective in 59% of iterations when the willingness-to-pay threshold was set to $100,000/life-years. CONCLUSION: Our model suggested that selective germline testing of patients with newly diagnosed pancreatic cancer is more cost-effective than universal testing. Additional research is needed to explore the impact of cascade testing of relatives on cost-effectiveness.

Total Neoadjuvant Therapy for Operable Pancreatic Cancer.

BACKGROUND: Overall survival (OS) for operable pancreatic cancer (PC) is optimized when 4-6 months of nonsurgical therapy is combined with pancreatectomy. Because surgery renders the delivery of postoperative therapy uncertain, total neoadjuvant therapy (TNT) is gaining popularity. METHODS: We performed a retrospective cohort study of patients with operable PC and compared TNT with shorter course neoadjuvant therapy (SNT). Primary outcomes of interest included completion of neoadjuvant therapy (NT) and resection of the primary tumor, receipt of 5 months of nonsurgical therapy, and median OS. RESULTS: We reviewed 541 consecutive patients from 2009 to 2019 including 226 (42%) with resectable PC and 315 (58%) with borderline resectable (BLR) PC. The median age was 66 years (IQR [59, 72]), and 260 (48%) patients were female. TNT was administered to 89 (16%) patients and SNT was administered to 452 (84%). Both groups were equally likely to complete intended NT and surgery (p = 0.90). Patients who received TNT and surgical resection were more likely to have a complete pathologic response (8% vs 4%, p < 0.01) and were more likely to receive at least 5 months of nonsurgical therapy (67% vs 45%, p < 0.01). The median OS was 26 months [IQR (15, 57)]; not reached among patients treated with TNT, and 25 months [IQR (15, 56)] among patients treated with SNT (p = 0.19). CONCLUSIONS: TNT ensures the delivery of intended systemic therapy prior to a complicated operation without decreasing the chance of successful surgery; a window of operability was not lost. Patients who can tolerate SNT will likely benefit from TNT.

Home Disposal Kits for Leftover Opioid Medications After Surgery: Do They Work?

BACKGROUND: Postoperative overprescribing is common, and many patients will have excess medications. An effective method to encourage disposal is lacking. We hypothesized that a convenient home disposal kit will result in more appropriate disposal of excess opioids. MATERIALS AND METHODS: We conducted a single-center prospective observational pilot study to evaluate the effectiveness of a postoperative opioid disposal kit. Patients in the intervention group received an opioid disposal kit and educational handout before discharge from the hospital. At the first follow-up visit, patients completed a survey in which they reported the remaining amount of pain medications from their original prescription and their plan for the excess medication. Patients were asked about risk factors for chronic opioid use. We used multivariable Poisson regression to identify independent factors associated with an increased likelihood of appropriate opioid disposal. RESULTS: The survey was offered to 904 patients with a response rate of 91.7%. After excluding those with missing data, 571 patients were included in the study. Overall, 83 (14.5%) patients never filled an opioid prescription, and 286 (60.0%) patients had tablets remaining at the time of the follow-up visit. Among those with tablets remaining, 52 received a home disposal kit, whereas 234 patients with tablets remaining did not. Patients who received the kit were more likely to dispose of opioid medications (54.9% versus 34.8%, relative risk = 1.8, 95% CI 1.3-2.5). No confounders were identified during multivariable analysis that increased a patient's likelihood of disposing excess medications. CONCLUSIONS: The provision of a convenient home disposal kit postoperatively increased patient-reported opioid disposal.

Mitotic stopwatch for the blast fungus Magnaporthe oryzae during invasion of rice cells.

To study nuclear dynamics of Magnaporthe oryzae, we developed a novel mitotic reporter strain with GFP-NLS (localized in nuclei during interphase but in the cytoplasm during mitosis) and H1-tdTomato (localized in nuclei throughout the cell cycle). Time-lapse confocal microscopy of the reporter strain during host cell invasion provided several new insights into nuclear division and migration in M. oryzae: (i) mitosis lasts about 5min; (ii) mitosis is semi-closed; (iii) septal pores are closed during mitosis; and (iv) a nucleus exhibits extreme constriction (approximately from 2µm to 0.5µm), elongation (over 5µm), and long migration (over 16µm). Our observations raise new questions about mechanisms controlling the mitotic dynamics, and the answers to these questions may result in new means to prevent fungal proliferation without negatively affecting the host cell cycle.

Sustainability and long-term effectiveness of the WHO surgical safety checklist combined with pulse oximetry in a resource-limited setting: two-year update from Moldova.

IMPORTANCE: Little is known about the sustainability and long-term effect of surgical safety checklists when implemented in resource-limited settings. A previous study demonstrated the marked, short-term effect of a structured hospital-wide implementation of a surgical safety checklist in Moldova, a lower-middle-income country, as have studies in other low-resource settings. OBJECTIVES: To assess the long-term reduction in perioperative harm following the introduction of a checklist-based surgical quality improvement program in a resource-limited setting and to understand the long-term effects of such programs. DESIGN, SETTING, AND PARTICIPANTS: Twenty months after the initial implementation of a surgical safety checklist and the provision of pulse oximetry at a referral hospital in Moldova, a lower-middle-income, resource-limited country in Eastern Europe, we conducted a prospective study of perioperative care and outcomes of 637 consecutive patients undergoing noncardiac surgery (the long-term follow-up group), and we compared the findings with those from 2106 patients who underwent surgery shortly after implementation (the short-term follow-up group). Preintervention data were collected from March to July 2010. Data collection during the short-term follow-up period was performed from October 2010 to January 2011, beginning 1 month after the implementation of the launch period. Data collection during the long-term follow-up period took place from May 25 to July 6, 2012, beginning 20 months after the initial intervention. MAIN OUTCOMES AND MEASURES: The primary end points of interest were surgical morbidity (ie, the complication rate), adherence to safety process measures, and frequency of hypoxemia. RESULTS: Between the short- and long-term follow-up groups, the complication rate decreased 30.7% (P = .03). Surgical site infections decreased 40.4% (P = .05). The mean (SD) rate of completion of the checklist items increased from 88% (14%) in the short-term follow-up group to 92% (11%) in the long-term follow-up group (P < .001). The rate of hypoxemic events continued to decrease (from 8.1 events per 100 hours of oximetry for the short-term follow-up group to 6.8 events per 100 hours of oximetry for the long-term follow-up group; P = .10). CONCLUSIONS AND RELEVANCE: Sustained use of the checklist was observed with continued improvements in process measures and reductions in 30-day surgical complications almost 2 years after a structured implementation effort that demonstrated marked, short-term reductions in harm. The sustained effect occurred despite the absence of continued oversight by the research team, indicating the important role that local leadership and local champions play in the success of quality improvement initiatives, especially in resource-limited settings.

Aesthetic Surgery Training during Residency in the United States: A Comparison of the Integrated, Combined, and Independent Training Models.

Background. Three educational models for plastic surgery training exist in the United States, the integrated, combined, and independent model. The present study is a comparative analysis of aesthetic surgery training, to assess whether one model is particularly suitable to provide for high-quality training in aesthetic surgery. Methods. An 18-item online survey was developed to assess residents' perceptions regarding the quality of training in aesthetic surgery in the US. The survey had three distinct sections: demographic information, current state of aesthetic surgery training, and residents' perception regarding the quality of aesthetic surgery training. Results. A total of 86 senior plastic surgery residents completed the survey. Twenty-three, 24, and 39 residents were in integrated, combined, and independent residency programs, respectively. No statistically significant differences were seen with respect to number of aesthetic surgery procedures performed, additional training received in minimal-invasive cosmetic procedures, median level of confidence with index cosmetic surgery procedures, or perceived quality of aesthetic surgery training. Facial aesthetic procedures were felt to be the most challenging procedures. Exposure to minimally invasive aesthetic procedures was limited. Conclusion. While the educational experience in aesthetic surgery appears to be similar, weaknesses still exist with respect to training in minimally invasive/nonsurgical aesthetic procedures.

Microsurgical head and neck reconstruction after oncologic ablation: a study analyzing health-related quality of life.

BACKGROUND: Evaluation of quality of life (QOL) measures is increasingly being valued as an essential parameter to determine treatment results after head and neck reconstruction. The present study was designed to evaluate the effect of microsurgical reconstruction on patient-reported QOL. METHODS: Patients undergoing microsurgical reconstruction after radical oncosurgical ablation of head and neck malignancies from March 2007 to March 2010 were included in the study. To assess health-related QOL, the following questionnaires were sent to patients who met inclusion criteria: European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30 [Version 3.0]) and Head and Neck Cancer Quality of Life Questionnaire (QLQ-H and N35). RESULTS: A total of 60 patients underwent microsurgical reconstruction of postablative head and neck defects during the study period. Twenty-one patients were successfully contacted, all of which completed the surveys. Satisfactory global QOL scores were achieved. Advanced age correlated with greater impairment for the ability to taste and smell (P = 0.05). Radiotherapy seemed to be associated with "sticky saliva"; although this was not statistically significant (P = 0.06). Recurrent disease at the time of surgical ablation and microsurgical reconstruction did not seem to have any appreciable impact on QOL. Finally, patients who developed postoperative complications had lower levels of "cognitive functioning" (P = 0.04), problems with "insomnia" (P = 0.04) and "social contact" (P = 0.03), and more commonly "felt ill" (P = 0.03). CONCLUSIONS: Improved global QOL scores were observed after microsurgical reconstruction of various head and neck defects when compared to reported pretreatment scores. Of the parameters analyzed, it seems that postoperative complications have the most profound effect on items assessed with the EORTC QLQ-C30 and H and N35 surveys. Our findings provide further scientific evidence that patients with head and neck malignancy benefit from surgical intervention with respect to postoperative QOL.

Should we continue to consider obesity a relative contraindication for autologous microsurgical breast reconstruction?

BACKGROUND: Obesity is not only a causative factor for premature mortality, it has also been demonstrated to be associated with an increased postoperative complication rate. As such, it has traditionally been considered a relative contraindication to autologous breast reconstruction. The purpose of this study was to assess whether this recommendation is justified. METHODS: A retrospective study was conducted analyzing the effect of obesity on complication rate after microsurgical autologous breast reconstruction using abdominal tissue. Patients undergoing breast reconstruction between November 2006 and February 2011 were included. In contrast to prior studies, only patients meeting criteria to undergo bariatric surgery were included in the study, thus, representing a particularly high-risk subset of patients (Group 1: BMI greater 40 kg/m(2); Group 2: BMI greater 35 kg/m(2) with co-morbidities). RESULTS: A total of 42 breast reconstructions were performed in 28 patients who met inclusion criteria. Surgical complications were seen in a total of 9 patients (p = 1.00). All complications were successfully managed conservatively and did not prolong hospitalization. No differences were seen among study groups with respect to donor-site (p = 0.57) and recipient-site complications (p = 1.00). Of note, no partial or total flap loss was seen in this study. CONCLUSIONS: Obesity is associated with a relatively high risk of minor complications postoperatively. However, complications can typically be managed non-operatively and on an outpatient basis with fairly minimal patient morbidity. We believe that obesity should not be considered a relative contraindication to autologous microsurgical breast reconstruction. Patients should, however, be informed preoperatively about their higher risk of postoperative complications.

The effect of preoperative radiotherapy on complication rate after microsurgical head and neck reconstruction.

BACKGROUND: The introduction of radiotherapy (XRT) has resulted in increased survival of patients diagnosed with head and neck malignancies. However, the potentially deleterious impact of radiotherapy on reconstructive efforts continues to be the subject of intense debate. The present study was designed to evaluate the effects of preoperative XRT on complication rates in patients undergoing microsurgical reconstruction of head and neck defects after oncosurgical resection. METHODS: A retrospective cohort study was conducted of all patients who underwent immediate microsurgical reconstruction of post-ablative defects over a 3-year period. Study subjects were divided into two groups: (1) those who did not receive XRT and (2) those who received preoperative XRT. Clinical variables examined and analysed included age, gender, co-morbid conditions, tobacco history, the presence of recurrent disease and ischaemia time. Outcomes of interest included length of intensive care unit (ICU) and hospital stay and postoperative complications. Complications were further classified as flap-related as well as 'medical'. RESULTS: A total of 60 patients were included in this study (group 1: 26 patients; group 2: 34 patients). Results were similar between the study groups with the exception of a higher rate of flap-related complications in patients undergoing XRT. Overall, 19 patients (31.7%) experienced flap-related complications, with 12% of the patients being in group 1 (N=3) versus 47% of patients being in group 2 (N=16) (p=0.003). CONCLUSIONS: Our data suggest that preoperative radiotherapy is associated with a significant increase in postoperative flap-related complications. However, these did not result in a prolonged hospital stay, reflecting the fact that the majority of flap-related complications can be managed on an outpatient basis. Although microsurgical reconstruction is frequently successful, patients with a history of XRT should be informed preoperatively about their increased risk of complications.

Abdominal wall strength: a matched-pair analysis comparing muscle-sparing TRAM flap donor-site morbidity with the effects of abdominoplasty.

BACKGROUND: Microsurgical autologous breast reconstruction has evolved significantly over the last three decades. The muscle-sparing transverse rectus abdominis musculocutaneous (TRAM), deep inferior epigastric artery perforator, and superficial inferior epigastric artery flaps have been developed to minimize abdominal donor-site morbidity. Assuming that harvest of the superficial inferior epigastric artery flap has the same impact on abdominal wall morbidity as performing an abdominoplasty, the authors designed a matched-pair analysis comparing patients' abdominal wall strength after muscle-sparing TRAM flap reconstruction with that after abdominoplasty. METHODS: A total of 104 patients were included in the study. Fifty-two TRAM flap patients were matched with 52 abdominoplasty patients for age and body mass index. Outcome measures included postoperative complications, particularly hernia and abdominal bulge formation. Two surveys were used to assess patient satisfaction as well as the impact of the procedure on everyday life. RESULTS: Both study groups were similar with regard to age, body mass index, past medical history, and postoperative complication rate, including hernia and abdominal bulge formation. Results were similar between the study groups, with the exception of a higher rate of satisfaction with the appearance of the abdominal scar among TRAM flap patients (p=0.03) as well a lower likelihood of TRAM flap patients to engaging in sporting activities postoperatively (p=0.01). CONCLUSIONS: In the present study, the muscle-sparing TRAM flap did not result in a higher rate of postoperative complications related to abdominal wall morbidity. Differences observed regarding the postoperative level of activity are unlikely to be related to the surgical insult to the abdominal wall.

Anthrax: a systematic review of atypical presentations.

During the 2001 US anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. During future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. Published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspnea, or chest pain and found to have abnormal lung examination results with pleural effusions or enlarged mediastinum. The purpose of this article is to evaluate whether atypical presentations of inhalational anthrax occur and to describe the features of these presentations. We define atypical presentations as those in patients with confirmed anthrax infection who do not have known cutaneous, gastrointestinal, or inhalational ports of entry. We reviewed the case reports of 42 patients with atypical anthrax (published between 1900 and 2004) that may have had an inhalational source of infection to evaluate whether their clinical presentations differed from the typical findings of inhalational anthrax. Patients with atypical anthrax were less likely to have cough, chest pain, or abnormal lung examination results than patients with typical inhalational anthrax (P<.05 for all comparisons). A previously published screening protocol for patients with suspected anthrax correctly identified 91% of patients with atypical presentations. We conclude that although uncommon, atypical presentations of inhalational anthrax likely occur. Timely diagnosis and treatment of patients with inhalational anthrax require clinical awareness of the full spectrum of signs and symptoms associated with inhalational anthrax.