Discrepancies in Financial Conflicts of Interest in Robotic Cardiothoracic Surgery Studies.

BACKGROUND: In academic surgery publications, self-reporting of conflicts of interest (COI) has often proved to be inaccurate. Here, we review the accuracy of COI disclosures for studies related to the use of robotic technology in cardiothoracic surgery and evaluate factors associated with increased discrepancies. METHODS: A literature search identified robotic surgery-related studies with at least 1 American author published between January 2015 and December 2020 from 3 major American cardiothoracic surgery journals (The Journal of Thoracic and Cardiovascular Surgery, The Annals of Thoracic Surgery, and Annals of Cardiothoracic Surgery). Industry payments from Intuitive Surgical (Intuitive) were collected with use of the Centers for Medicare and Medicaid Open Payments database. COI discrepancies were identified by comparing author declaration statements with payments found for the year of publication and the year prior (24-month period). RESULTS: A total of 144 studies (764 authors) were identified. At least 1 author of 112 studies (78%) had received payments from Intuitive. At least 1 author of 98 studies (68%) had received an undeclared payment from Intuitive. Authors who accurately disclosed payments received significantly higher median payments compared with authors who did not ($16,511 [interquartile range, $6389-$159,035] vs $1762 [interquartile range, $338-$7500]; P < .0001). Last authors were significantly more likely to have a COI discrepancy compared with middle and first authors (P = .018; P = .0015). CONCLUSIONS: Most studies investigating the use of robotic technology in cardiothoracic surgery did not accurately declare COI with Intuitive. This study highlights the need for improved accuracy of reporting industry sponsorship by publishing authors.

A Lower Tidal Volume Regimen during One-lung Ventilation for Lung Resection Surgery Is Not Associated with Reduced Postoperative Pulmonary Complications.

BACKGROUND: Protective ventilation may improve outcomes after major surgery. However, in the context of one-lung ventilation, such a strategy is incompletely defined. The authors hypothesized that a putative one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after thoracic surgery. METHODS: The authors merged Society of Thoracic Surgeons Database and Multicenter Perioperative Outcomes Group intraoperative data for lung resection procedures using one-lung ventilation across five institutions from 2012 to 2016. They defined one-lung protective ventilation as the combination of both median tidal volume 5 ml/kg or lower predicted body weight and positive end-expiratory pressure 5 cm H2O or greater. The primary outcome was a composite of 30-day major postoperative pulmonary complications. RESULTS: A total of 3,232 cases were available for analysis. Tidal volumes decreased modestly during the study period (6.7 to 6.0 ml/kg; P < 0.001), and positive end-expiratory pressure increased from 4 to 5 cm H2O (P < 0.001). Despite increasing adoption of a "protective ventilation" strategy (5.7% in 2012 vs. 17.9% in 2016), the prevalence of pulmonary complications did not change significantly (11.4 to 15.7%; P = 0.147). In a propensity score matched cohort (381 matched pairs), protective ventilation (mean tidal volume 6.4 vs. 4.4 ml/kg) was not associated with a reduction in pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32). In an unmatched cohort, the authors were unable to define a specific alternative combination of positive end-expiratory pressure and tidal volume that was associated with decreased risk of pulmonary complications. CONCLUSIONS: In this multicenter retrospective observational analysis of patients undergoing one-lung ventilation during thoracic surgery, the authors did not detect an independent association between a low tidal volume lung-protective ventilation regimen and a composite of postoperative pulmonary complications.

Prolonged Opioid Use Associated With Reduced Survival After Lung Cancer Resection.

BACKGROUND: Lung cancer remains the leading cause of cancer death worldwide and the search for modifiable risk factors to improve survival is ongoing. There is a growing appreciation for a biological relationship between opioids and lung cancer progression. Our goal was to evaluate the association between perioperative opioid use and long-term survival after lung cancer resection. METHODS: A retrospective analysis of 2006 to 2012 Surveillance, Epidemiology, and End Results Medicare datasets identified all patients undergoing pulmonary resection for non-small cell lung cancer stages I to III. Patients were stratified by filling opioid prescriptions only 30 days before or after surgery (standard group), filling opioid prescriptions greater than 30 days before surgery (chronic group), or filling opioid prescriptions greater than 90 days after surgery but not before surgery (prolonged group). Kaplan-Meier survival analysis compared each group; risk-adjusted survival analysis was performed using the Cox proportional hazards model. RESULTS: We identified 3273 patients, including 1385 in the standard group (42.3%), 1441 in the chronic group (44.0%), and 447 in the prolonged group (13.7%). Of previously opioid-naive patients, 447 of 1832 (24.4%) became new prolonged opioid users. Kaplan-Meier survival analysis illustrated lower overall and disease-specific survival in chronic and prolonged opioid groups (both P < .01). After risk adjustment, chronic (hazard ratio = 1.27; 95% confidence interval, 1.09-1.47; P < .01) and prolonged (hazard ratio = 1.42; 95% confidence interval, 1.17-1.73; P < .01) opioid use were independently associated with reduced long-term survival. CONCLUSIONS: Chronic and prolonged opioid use were independently associated with reduced long-term, disease-specific survival after lung cancer resection. These findings provide epidemiologic support for a biological relationship between opioid use and lung cancer progression.

Use of endoscopic ultrasound in pre-treatment staging of esophageal cancer did not alter management plan.

BACKGROUND: Initial staging of esophageal cancer relies on EUS in addition to FDG-PET/CT. It is our hypothesis that with the advancement of FDG-PET/CT staging, endoscopic ultrasound may not be required for initial staging in all cases. The purpose of this study is to analyze whether EUS affects initial treatment stratification in patients diagnosed with esophageal cancer. METHODS: A retrospective database at the University of Virginia was queried for patients diagnosed with esophageal squamous cell carcinoma and adenocarcinoma who underwent EGD with EUS and FDG-PET/CT at their initial evaluation from 10/2013 to 5/2017. Two thoracic surgeons were asked to determine appropriate management for each case. Options included surgical resection, neoadjuvant chemoradiotherapy followed by resection, definitive chemoradiotherapy, or chemotherapy with or without palliative radiation. Both surgeons received the FDG-PET/CT report along with the EGD report. For each case, one or both surgeons were randomly allocated to review EUS results in addition to the clinical information. The treatment decisions of each thoracic surgeon were compared to determine if EUS reports impacted clinical management. Simple and weighted correlation coefficients (kappa) were calculated to compare agreement of treatment choices between the two surgeons using McNemars test. Conditional logistic regression was used to assess the influence of EUS on the treatment recommendations. RESULTS: A total of 50 patients (44 male and 6 female) were enrolled and data was collected. The thoracic surgeons agreed on treatment decisions in 39 cases and disagreed on 11 cases. Agreement between surgeons was good despite lack of EUS information for one surgeon on each case (weighted Kappa =0.73, 95% CI: 0.57-0.89). Using conditional logistic regression, EUS did not have a statistically independent association with agreement on treatment plan (P for model =0.17). CONCLUSIONS: EUS did not have a statistically independent association with agreement on treatment plan for newly diagnosed esophageal cancer (P for model =0.17). Our findings suggest that EUS may not be necessary in the algorithm for the initial staging of every case of esophageal cancer. Selective, rather than mandatory use of EUS seems warranted.

Poor Performance Flagging Is Associated With Fewer Transplantations at Centers Flagged Multiple Times.

BACKGROUND: Lung transplantation outcomes are heavily scrutinized, given the high stakes of these operations, yet the Center for Medicare and Medicaid Services (CMS) method of using Scientific Registry of Transplant Recipients (SRTR) risk-adjusted outcomes to identify underperforming centers is controversial. We hypothesized that CMS flagging results in conservative behavior for recipient and organ selection, resulting in fewer patients added to the waitlist and fewer transplantations performed. METHODS: SRTR reports from July 2012 through July 2017 were included. Center characteristics were compared, stratified by number of flagging events. The impact of flagging for underperformance on risk aversion outcomes was analyzed using a mixed-effects regression model. RESULTS: A total of 72 centers had reported SRTR data during the study period. Of these, 21 centers (29%) met flagging criteria a median of 2 times (interquartile range, 1 to 4 times) for a total of 53 events. Flagging had no statistically significant impact on waitlist or transplantation volume and patient selection by mixed-effects modeling. Despite similar average expected 1-year survival (86.6% versus 87.7%, p = 0.27), centers that were flagged only once added more patients per year to the waitlist (16.3 patients versus 7.8 patients, p = 0.01) and performed more transplantations per year (28.4 transplantations versus 11.1 transplantations, p = 0.01). CONCLUSIONS: This analysis defines center-level trends in lung transplantation after CMS flagging. Contrary to our primary hypothesis, flagging did not result in temporal center-level changes. However, programs on prolonged probation demonstrated reduced activity, which likely indicates a shift to higher performing centers.

Pulmonary malakoplakia secondary to Rhodococcus equi infection mimicking a lung neoplasm in a lung transplant recipient.

Pulmonary masses occasionally occur after lung transplantation and vary in etiology, which includes malignant and benign conditions, such as infection. Here, we report a case of a patient presenting with a lung mass 3 years after lung transplant. To our knowledge, this is the first described case of pulmonary malakoplakia due to Rhodococcus equi infection in an allograft post-lung transplantation. This case outlines the challenges of differentiating benign from malignant masses after transplantation.

Ex Vivo Assessment of Porcine Donation After Circulatory Death Lungs That Undergo Increasing Warm Ischemia Times.

BACKGROUND: Increased utilization of donation after circulatory death (DCD) lungs may help alleviate the supply/demand mismatch between available donor organs and lung transplant candidates. Using an established porcine DCD model, we sought to determine the effect of increasing warm ischemia time (WIT) after circulatory arrest on lung function during ex vivo lung perfusion (EVLP). METHODS: Porcine donors (n = 15) underwent hypoxic cardiac arrest, followed by 60, 90, or 120 minutes of WIT before procurement and 4 hours of normothermic EVLP. Oxygenation, pulmonary artery pressure, airway pressure, and compliance were measured hourly. Lung injury scores were assessed histologically after 4 hours of EVLP. RESULTS: After EVLP, all 3 groups met all the criteria for transplantation, except for 90-minute WIT lungs, which had a mean pulmonary artery pressure increase greater than 15%. There were no significant differences between groups as assessed by final oxygenation capacity, as well as changes in pulmonary artery pressure, airway pressure, or lung compliance. Histologic lung injury scores as well as lung wet-to-dry weight ratios did not significantly differ between groups. CONCLUSIONS: These results suggest that longer WIT alone (up to 120 minutes) does not predict worse lung function at the conclusion of EVLP. Expanding acceptable WIT after circulatory death may eventually allow for increased utilization of DCD lungs in procurement protocols.

Electromagnetic navigational bronchoscopic airway recanalization in patients with vanishing bronchus.

BACKGROUND: Stenosis is the most frequent airway complication after lung transplantation. When complete obstruction is diagnosed without possibility of recanalization, options are generally limited to either resection or retransplantation, both associated with increased morbidity and mortality. We describe our experience with a novel technique using electromagnetic navigational bronchoscopy (ENB) to recanalize the occluded airway after lung transplantation. METHODS: Patients who underwent lung transplantation between 2010 and 2016 with subsequent development of complete airway obstruction and failed conventional recanalization attempts were included in this study. All patients underwent attempted recanalization using ENB. Primary outcomes included success of the technique and long-term patency. Secondary outcomes included procedure-related complications. RESULTS: Four patients met inclusion criteria and underwent attempted recanalization using the ENB platform. Location of the obstruction was the bronchus intermedius in two patients, the lingular bronchus in one patient, and the left basilar bronchus in one patient. Mean length of stenosis was 8.8 mm. Three patients (75%) were successfully recanalized and all airways remain patent at 1, 48, and 66 mo. There were no procedure-related complications. The one patient who was unable to be recanalized successfully underwent bilobectomy and died 7 mo later. CONCLUSIONS: ENB is a feasible method of airway recanalization in select patients with bronchial occlusion after lung transplantation. ENB recanalization spares lung parenchyma and avoids risks associated with surgical resection and retransplantation. This novel technique can be added to the armamentarium for thoracic surgeons who diagnose and treat this complicated problem.

Isolated Hemorrhagic Pericardial Effusion After Foreign Body Ingestion.

Foreign body ingestion is one of the many potential causes of esophageal perforation. In this case report we describe a man who presented with chest pain and was found to have an isolated hemorrhagic pericardial effusion secondary to occult ingestion and pericardial migration of a metallic foreign body. Surgical management was successful, and the patient has recovered well.

Implementing a Thoracic Enhanced Recovery Program: Lessons Learned in the First Year.

BACKGROUND: To minimize the stress of operations, improve the patient experience, reduce variability, and optimize resource utilization, we implemented a thoracic enhanced recovery after surgery (ERAS) protocol and evaluated progress after 1 year. METHODS: Two protocols were developed: video-assisted thoracic surgery (ERAS-VATS) and thoracotomy (ERAS-T). Each incorporated preoperative patient education, carbohydrate loading, opioid-sparing analgesia, conservative fluid management, and early ambulation. Patient outcomes, length of stay, pain scores, opioid use, fluid administration, and cost for ERAS patients were compared with historic controls from the year before program initiation. RESULTS: Historic VATS (n = 162) were compared with 81 ERAS-VATS patients. Median postoperative morphine equivalents (86 versus 22 mg, p < 0.0001), total fluid balance (1279 versus 227 mL, p < 0.0001), and mean inflation adjusted hospital costs ($20,169 versus $14,870, p = 0.0003) all decreased significantly. Historic thoracotomy patients (n = 62) were compared with 58 ERAS-T patients. Median postoperative morphine equivalents (130 versus 54 mg, p < 0.0001), total fluid balance (788 versus -489 mL, p = 0.012), length of stay (6.0 versus 4.0 days, p = 0.009), and mean inflation adjusted hospital costs ($41,950 versus $26,089, p < 0.00001) all decreased significantly. CONCLUSIONS: Implementation of thoracic ERAS is a dynamic process with potential to improve outcomes in thoracic surgical procedures. In the first year we shortened length of stay, decreased opioid usage, minimized fluid overload, and decreased hospital costs.

Cardiothoracic and Vascular Surgeons Achieve High Rates of K Award Conversion Into R01 Funding.

BACKGROUND: Obtaining National Institutes of Health (NIH) R01 funding remains extremely difficult. The utility of career development grants (K awards) for achieving the goal of R01 funding remains debated, particularly for surgeon-scientists. We examined the success rate for cardiothoracic and vascular (CTV) surgeons compared with other specialties in converting K-level grants into R01 equivalents. METHODS: All K (K08 and K23) grants awarded to surgeons by the NIH between 1992 and 2017 were identified through NIH Research Portfolio Online Report Tools (RePORTER), an online database combining funding, publications, and patents. Only grants awarded to CTV surgeons were included. Grants active within the past year were excluded. Mann-Whitney U tests and χ2 tests were used to compare groups. RESULTS: During this period, 62 K grants were awarded to CTV surgeons. The analysis excluded 16 grants that were still active within the last year. Twenty-two (48%) of the remaining K awardees successfully transitioned to an R01 or equivalent grant. Awardees with successful conversion published nine publications per K grant compared with four publications for those who did not convert successfully (p = 0.01). The median time for successful conversion to an R grant was 5.0 years after the K award start date. Importantly, the 10-year conversion rate to R01 was equal for CTV surgeons compared with other clinician-investigators (52.6% vs 42.5%). CONCLUSIONS: CTV surgeons have an equal 10-year conversion rate to the first R01 award compared with other clinicians. These data suggest that NIH achieves a good return on investment when funding CTV surgeon-scientists with K-level funding.

Variability in Integrated Cardiothoracic Training Program Curriculum.

BACKGROUND: Development of curricula that appropriately progress a resident from medical school graduate to fully trained cardiothoracic surgeon is a key challenge for integrated cardiothoracic training programs. This study examined variability and perceived challenges in integrated curricula. METHODS: Responses to the 2016 TSDA/TSRA survey that accompanies the annual in-training exam taken by current cardiothoracic surgery residents were analyzed. Standard statistical methods were utilized to examine trends in participant responses. RESULTS: General surgery experience decreased with post-graduate year, whereas cardiac operative experience increased. Rotations in a wide variety of adjunct fields were common. The majority (87%) of respondents reported had dedicated cardiothoracic intensive care unit (ICU) rotations, and surgical ICU and cardiac care unit rotations were less common (68% and 42%, respectively). The most common surgical subspecialty rotations were vascular (94%) and acute care surgery (88%), with a wide range of clinical exposure (ie, 3-44 weeks for vascular). Importantly, 52% felt competition with general surgery residents for experience and 22.5% of general surgery rotations were at hospitals without general surgery residents. Perceived challenges included optimization of rotations (78%), faculty allowing residents to perform case components (60%), faculty teaching in the operating room (29%), and improving surgical experience on general surgery rotations (19%). CONCLUSIONS: Significant variation exists in integrated cardiothoracic surgery curricula. Optimization of rotations, access to surgical experience, and integration with general surgery appear to be the most significant perceived challenges. These data suggest that optimization of early clinical and surgical experience within institutions could improve trainee preparedness for senior cardiothoracic surgery training.

The Future of the Academic Cardiothoracic Surgeon: Results of the TSRA/TSDA In-Training Examination Survey.

BACKGROUND: Traditionally cardiothoracic residents spent dedicated research time during general surgery equipping them for a potential academic career. Recent changes in training paradigms, including integrated programs that may not include research time, could affect the development of future academic cardiothoracic surgeons. METHODS: Responses to the 2015 Thoracic Surgery Directors' Association/Thoracic Surgery Residents' Association survey accompanying the in-training examination taken by current cardiothoracic surgery residents were analyzed. Three hundred fifty-four residents were surveyed with a response rate of 100%, although one was excluded from the analysis because of inconsistencies in responses. Statistical analysis included χ(2), Fisher's exact test, and multinomial logistic regression with significance set at a probability value of 0.05. RESULTS: Two hundred sixty-seven of 353 residents (76%) intended on performing research as part of their careers. Integrated residents as opposed to traditional residents (85% versus 69%; p = 0.003), males (78% versus 65%; p = 0.02), those pursuing additional training (85% versus 69%; p = 0.003), and those interested in academic careers (93% versus 33%; p < 0.001) were more likely to pursue research. Differences were also noted in specialty interest, with congenital and heart failure specialties most likely to pursue research careers (92% and 100%, respectively; p < 0.05). Residents intending on research careers were more likely to have had previous research experience, and the most common type of intended research was clinical outcomes (78%). On multinomial logistic regression, previous clinical outcomes research and academic practice were identified as predictors of a research career (odd ratios of 9.7 and 4.1, respectively; each p < 0.05). CONCLUSIONS: The majority of residents plan on pursuing research during their careers. Previous research experience appears to be a key determinant as well as specialty interest.

Gender and Cardiothoracic Surgery Training: Specialty Interests, Satisfaction, and Career Pathways.

BACKGROUND: The cardiothoracic surgical workforce is changing. Although 5% of practicing surgeons are women, 20% of current cardiothoracic surgery residents are women. The purpose of this study was to evaluate the influence of gender on specialty interest, satisfaction, and career pathways of current residents. METHODS: Responses to the mandatory 2015 Thoracic Surgery Residents Association/Thoracic Surgery Directors Association in-training examination survey taken by 354 residents (100% response rate) were evaluated. The influence of gender was assessed with the use of standard univariate analyses. RESULTS: Women accounted for 20% of residents, and the percentage did not vary with postgraduate year or program type (traditional versus integrated). Although no differences were found between the genders related to specialty interest, academic versus private practice career, or pursuit of additional training, women were more likely to pursue additional training in minimally invasive thoracic surgery (10% versus 2.5%, p = 0.001) and less likely to perform research in their careers (65% versus 88%, p = 0.043). Although women were equally satisfied with their career choice, had similar numbers of interviews and job offers, and felt equally prepared for their boards, graduating women felt less prepared technically (77% versus 90%, p = 0.01) and for practicing independently (71% versus 87%, p = 0.01). Women were less likely to be married (26% versus 62%, p < 0.001) and have children (19% versus 49%, p < 0.001). CONCLUSIONS: Although career satisfaction and specialty interest were similar between the genders, women were less likely to intend to perform research during their careers despite similar previous research experience. Women also demonstrated lower rates of marriage and childbearing compared with their male counterparts.

Operative endoscopy of the airway.

Airway endoscopy has long been an important and useful tool in the management of thoracic diseases. As thoracic specialists have gained experience with both flexible and rigid bronchoscopic techniques, the technology has continued to evolve so that bronchoscopy is currently the foundation for diagnosis and treatment of many thoracic ailments. Airway endoscopy plays a significant role in the biopsy of tumors within the airways, mediastinum, and lung parenchyma. Endoscopic methods have been developed to treat benign and malignant airway stenoses and tracheomalacia. And more recently, techniques have been conceived to treat end-stage emphysema and prolonged air leaks in select patients. This review describes the abundant uses of airway endoscopy, as well as technical considerations and limitations of the current technologies.

Characterizing the Operative Experience of Cardiac Surgical Trainees: What Are Residents Really Doing in the Operating Room?

BACKGROUND: The present study aimed to describe and compare the operative experience of cardiothoracic surgical residents for basic and advanced cardiac surgical procedures. METHODS: Data were obtained from the 2015 Thoracic Surgery Directors Association Survey administered to all thoracic surgical residents taking the yearly In-Service Training Examination (n = 356). Residents were asked whether they routinely served as the operative surgeon on various cardiac operations and operative tasks. Results were stratified by postgraduate year (PGY), residency type, and primary career interest. RESULTS: The survey response rate was 100%. Considering all training pathways, only 2 of 13 cardiac operations surveyed were routinely performed by graduating chief residents as the operative surgeon: coronary artery bypass grafting (CABG; 92%) and aortic valve replacement (AVR; 88%). Off-pump CABG, minimally invasive mitral valve operation, and transcatheter aortic interventions were infrequently (<30% of the time) performed by graduating residents as the operative surgeon. These results were similar when residents with a career interest in general thoracic surgery were excluded from the analysis. For the operative progression of integrated 6-year (I-6) residents, most began to routinely cannulate for cardiopulmonary bypass, perform proximal coronary anastomoses, and harvest the mammary artery during PGY3. The majority (>50%) of I-6 residents performed CABG as the operative surgeon by PGY4. CONCLUSIONS: There is pronounced heterogeneity in the cardiac operative experience of cardiothoracic surgical residents in the United States, with only CABG and AVR routinely performed by graduating residents as the operative surgeon. This heterogeneity may lead to insufficient training in certain procedures for many graduates.

A Long Gastrojejunostomy Is Associated With Decreased Incidence and Severity of Delayed Gastric Emptying After Pancreaticoduodenectomy.

OBJECTIVES: Delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) is associated with increased hospital length of stay (LOS) and health care costs. We hypothesized that a long gastrojejunostomy for PD (LGPD) is associated with decreased incidence of DGE. METHODS: Data were reviewed from patients who underwent standard PD (SPD), pylorus-preserving PD (PPPD), or LGPD with a 9-cm-long anastomosis between August 2000 and July 2010. Primary outcomes included presence and grade of DGE and LOS. The International Study Group of Pancreatic Surgery definition was used to define DGE. RESULTS: A total of 194 PDs (28 SPDs, 82 PPPDs, and 84 LGPDs) were performed. The rates of DGE were 46.4%, 37.8%, and 16.7%, respectively (P = 0.001). The LGPD was associated with fewer grades B/C DGE (2.4%) compared to SPD (10.7%) and PPPD (17.5%). Rates of postoperative abdominal fluid collection and abscess were similar among the groups. Patients with DGE had significantly longer LOS (14.0 vs 7.0 days, P < 0.001). CONCLUSIONS: This is the first study evaluating the effect of a long gastrojejunostomy on the incidence of DGE after PD. The LGPD is associated with significantly decreased DGE compared to SPD and PPPD and warrants further exploration as a means to improve outcome for patients who undergo PD.

Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis.

Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ≥1.0 cm (79.3% vs. 8.7%, P=0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P=0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were <5 cm; however, none were <3 cm. Increased serum CA19-9 level (>37 U/L) was also more common in the invasive tumors (64% vs. 23%, P=0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P=0.000). The pT2 (>2 cm) invasive tumors had a worse prognosis than pT1 (≤2 cm) tumors (P=0.000), albeit 3 patients with T1a (<0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS-depleted areas with lower progesterone receptor expression. Invasion is not seen in small tumors (<3 cm) and those lacking intracystic papillary (mural) nodules of ≥1 cm, thus making the current branch-duct intraductal papillary mucinous neoplasm management protocols also applicable to MCNs.