Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Survival Outcomes of Optimally Treated Colorectal Metastases: The Importance of R0 Status in Surgical Treatment of Hepatic and Peritoneal Surface Disease.

BACKGROUND: Although colorectal hepatic metastases (HM) and peritoneal surface disease (PSD) are distinct biologic diseases, they may have similar long-term survival when optimally treated with surgery. METHODS: This study retrospectively reviewed prospectively managed databases. Patients undergoing R0 or R1 resections were analyzed with descriptive statistics, the Kaplan-Meier method, and Cox regression. Survival was compared over time for the following periods: 1993-2006, 2007-2012, and 2013-2020. RESULTS: The study enrolled 783 HM patients undergoing liver resection and 204 PSD patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Compared with PSD patients, HM patients more often had R0 resections (90.3% vs. 32.4%), less often had pre-procedure chemotherapy (52.4% vs. 92.1%), and less often were functionally independent (79.7% vs. 95.6%). The 5-year overall survival for HM was 40.9%, with a median survival period of 45.8 months versus 25.8% and 33.4 months, respectively, for PSD (p < 0.05). When stratified by resection status, R0 HM and R0 PSD did not differ significantly in median survival (49.0 vs. 45.4 months; p = 0.83). The median survival after R1 resection also was similar between HM and PSD (32.6 vs. 26.9 months; p = 0.59). Survival between the two groups again was similar over time when stratified by resection status. The predictors of survival for HM patients were R0 resection, number of lesions, intraoperative transfusion, age, and adjuvant chemotherapy. For the PSD patients, the predictors were peritoneal cancer index (PCI) score, estimated blood loss (EBL), and female gender. CONCLUSION: The study showed that R0 resections are associated with improved outcomes and that median survival is similar between HM and PSD patients when it is achieved. Surveillance and treatment strategies that facilitate R0 resections are needed to improve results, particularly for PSD.

Pancreaticoduodenectomy After Liver Transplantation: A Single-Center Experience.

BACKGROUND: The aim of this study is to report the feasibility and short-term outcomes of pancreaticoduodenectomy (PD) in patients who have undergone orthotopic liver transplantation (OLT). METHODS: We performed a retrospective review of a prospectively maintained pancreatic surgical database for all patients undergoing pancreaticoduodenectomy (PD) after liver transplant from January 1995 until June 2022. Demographics, indications for pancreatic resection, liver transplant and time from liver transplant to PD were reported. Operative mortality and morbidity were recorded within 90 days of surgery. Continuous variables were recorded as mean and range, while categorical variables were summarized using frequency and percentage. Postoperative complications within 90 days from PD were graded based on Clavien-Dindo classification with major complication recorded as grade IIIa or higher. Additionally, a comprehensive literature review was performed. RESULTS: A total of 916 patients who underwent PD at our institution between January 1995 and June 2022 were identified, and 9 patients had previous OLT. Five patients were females and 4 males with a mean age of 65 years (range 51-78). Average body mass index (BMI) was 30.8. Two patients had major complications, and three patients had minor complications. No clinically relevant POPF, PPH or DGE were observed. One patient died within 90 days from PD due to ischemic biliary pancreatic limb causing intrabdominal sepsis. CONCLUSION: Although uncommon, PD after OLT is feasible with acceptable outcomes at high volume institutions and if performed by experienced surgeons.

Venous thromboembolism and bleeding after hepatectomy: role and impact of risk adjusted prophylaxis.

Venous thromboembolism (VTE) occurs in 2-6% of post-hepatectomy patients and is associated with increased mortality and morbidity. The use of VTE risk assessment models in hepatectomy cases remains unclear. Our study aimed to determine the use and impact of Caprini guideline indicated VTE prophylaxis following hepatectomy. Hepatectomy cases performed during 2016-2021 were included. Caprini score and VTE prophylaxis were determined retroactively, and VTE prophylaxis was categorized as appropriate or inappropriate. The primary outcome was the receipt of appropriate prophylaxis, and secondary outcomes were postoperative VTE and bleeding. Statistical analyses included Fisher Exact test, Kruskal-Wallis, Pearson Chi-Square test, and multivariate regression models. R Statistical software was used for analysis. A p-value < 0.05 or 95% Confidence Interval (CI) excluding 1 was considered significant. A total of 1955 hepatectomy cases were analyzed. Patient demographics were similar between study cohorts. Inpatient, 30- and 90-day VTE rates were 1.28%, 0.56%, and 1.24%, respectively. By Caprini guidelines, 59% and 4.3% received appropriate in-hospital and discharged VTE prophylaxis, respectively. Inpatient VTE (4.5-fold) and mortality (9.5-fold) were lower in patients receiving appropriate prophylaxis. All discharged VTE and mortality occurred in patients not receiving appropriate prophylaxis. Inpatient, 30- and 90-day bleeding rates were 8.4%, 0.62%, and 0.68%, respectively. Appropriate prophylaxis did not increase postoperative bleeding. Increasing Caprini score inversely correlated with receiving appropriate prophylaxis (OR 0.38, CI 0.31-0.46) at discharge, and appropriate prophylaxis did not correlate with bleeding risk (OR 0.79, CI 0.57-1.12). Caprini guideline indicated prophylaxis resulted in reduced VTE complications without increasing bleeding risk.

Risk adjusted venous thromboembolism prophylaxis following pancreatic surgery.

This study analyzes pancreatectomy cases performed between 2016 and 2021 to determine the impact of using Caprini guideline indicated VTE prophylaxis on VTE and bleeding complications. This is a retrospective study of cases performed in a single academic health care system, in which Caprini score and VTE prevention measures were determined retroactively and prevention practices binarized as appropriate or not appropriate. Univariate and multivariate analyses were performed of 1,299 pancreatectomy case. Most patients were stratified as high risk for postoperative VTE. Receiving appropriate VTE prophylaxis during admission was associated with a 3-fold reduction in VTE complications (0.82% vs. 2.64%, p=0.01) without increasing bleeding complications. All VTE complications occurring with 30-day (1.2%) and 90-day (2.7%) from hospital discharged occurred in those not receiving appropriate prophylaxis, and discharged bleeding complications were also not associated with receivng appropriate discharged VTE prophylaxis. The findings our the study are significant as it highlights the ongoing need for standardization in VTE risk assessment and prevention measures to increase compliance to risk adjusted VTE prevention practice guidelines, thus reducing preventable VTE complications and potentially associated morbidity and mortality.

Comparison of complications for cirrhotic versus non-cirrhotic patients undergoing pancreaticoduodenectomy.

PURPOSE: To compare the outcomes between patients with cirrhosis and those without who have undergone pancreatoduodenectomy (PD) in our institution. METHODS: A review of patients undergoing PD from the time period of January 2010 to December 2020 was performed. Patients that have undergone open or laparoscopic PD and had liver cirrhosis diagnosed prior to surgery were included and matched on a 1:2 basis with non-cirrhotic patients based on age, gender, Eastern Cooperative Oncology Group (ECOG), and date of surgery. Data was obtained from our medical records and ten major postoperative complications variables were compared to the matched group. RESULTS: Overall, 16 patients with cirrhosis were compared to 32 matched controls. No significant differences were found in pancreatic fistula (18.8% vs. 21.8%; P= 1.000), hemorrhage (6.3% vs. 6.2%; P= 1.000), delayed gastric emptying (6.3% vs. 15.6%; P= 0.648), wound infection (0% vs. 9.3%; P= 0.541), and intraabdominal abscess (31.2% vs 6.2%; 0.4998) for cirrhotic vs. non-cirrhotic respectively. There were no postop ileus, gastric fistula, mesenteric portal thrombosis, biliary fistula, and abdominal ischemic event in either group. The average length of stay for both groups was similar (6.9 vs. 9.3 days; P= 0.4019). There were no mortalities and major morbidity was similar (37.5% vs 34.3%; P=0.3549). One patient required readmission for liver-related decompensation with full recovery. CONCLUSION: PD in patients with cirrhosis can be safe and feasible in well-selected patients. In a high-volume institution, postoperative complications are similar to those patients without cirrhosis of the liver.

Routine prophylactic abdominal drainage versus no-drain strategy after distal pancreatectomy: A multicenter propensity score matched analysis.

BACKGROUND: /Objectives Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). Traditionally, surgical drains are placed routinely after DP, but some question its efficacy and postulate that the use of drains may convert a self-limiting postoperative collection into a POPF. This study aimed to compare outcomes between three institutions with varying drainage strategies. METHODS: The study is a retrospective propensity score-matched analysis of intraoperative prophylactic drain placement during DP (2010-2019). The primary outcome is major morbidity. Propensity score matching was used to obtain comparable groups. RESULTS: Overall, 963 patients after DP were included. One center did not place a surgical drain routinely, but decided to place a drain when unsatisfactory pancreatic closure occurred. Prophylactic abdominal drains were placed in 805 patients (84%) of which 74 could be matched to 74 patients without a drain. The rate of major morbidity (8% vs 19%, p = 0.054) and radiological interventions (5% vs 12%, p = 0.147) were non-significantly lower in the no-drain group as compared to the prophylactic drain group, respectively. The rates of POPF (4% vs 16%, p = 0.014) were lower in the no-drain group. CONCLUSION: In this international retrospective multicenter study, a selective no-drain strategy after DP was not associated with higher rates major morbidity or radiological interventions as compared to routine prophylactic abdominal drainage. Although the rate of POPF was lower in the no-drain group, randomized trials should confirm the safety and outcome of a no-drain strategy after DP.

Perioperative chemotherapy for resectable colorectal liver metastases: Analysis from the Colorectal Operative Liver Metastases International Collaborative (COLOMIC).

BACKGROUND: Chemotherapy has been increasingly combined with surgery as multimodality treatment for resectable colorectal-liver metastases (CLM). There is paucity of clinical data addressing optimal timing of chemotherapy relative to surgery. We examined outcomes of patients undergoing hepatectomy for resectable CLM. METHODS: Seven hundred and eighteen patients treated with hepatectomy for CLM were analyzed from five hepatobiliary institutions between 2000 and 2018. Overall survival (OS) was measured from time of hepatectomy for patients receiving: surgery alone, neoadjuvant, adjuvant, and neoadjuvant-plus-adjuvant (perioperative) chemotherapy. Kaplan-Meier analysis was performed to detect differences in OS between treatment groups. Single- and multi-variable analysis with Cox proportional hazards were run for OS between groups. RESULTS: One hundred and thirty-seven patients (19.08%) received surgery, 104 (14.48%) received neoadjuvant-only, 214 (29.81%) received adjuvant-only, and 263 (36.63%) received perioperative chemotherapy; with median OS of 48.20, 46.83, 56.27, and 49.93 months, respectively. No differences in median OS were seen between groups on Kaplan-Meier analysis. No significant difference in Charlson-Deyo comorbidity status was seen between groups (p = 0.853), while significant difference was seen in maximum tumor size (p = 0.0023). On multivariate analysis, adjuvant (p = 0.010) and perioperative (p = 0.020) chemotherapy were independently associated with OS compared to surgery alone. DISCUSSION: Despite group differences, chemotherapy after surgery was independently associated with improved OS in CLM.

Outcomes after repeat hepatectomy for colorectal liver metastases from the colorectal liver operative metastasis international collaborative (COLOMIC).

BACKGROUND: Resection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS. RESULTS: A total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05). CONCLUSION: In CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.

Pancreatic metastasectomy of renal cell carcinoma: a single institution experience.

INTRODUCTION: Renal cell carcinoma (RCC) is the most common primary neoplasia that metastasizes to the pancreas. Pancreatic metastasis (PM) occur in asymptomatic older patients and are identified during follow up. If resectable, surgery is the treatment of choice for long term survival. Our goal is to analyze outcomes of patients with RCC-PM. MATERIAL AND METHODS: We reviewed all patients with metastatic RCC (mRCC) who underwent resection, from known primary RCC and RCC-PM. RESULTS: There were 16 patients (mean age of 67 ± 8 years, male 8 (50%), mean BMI 29 ± 5.36 kg/m2). Half of them were asymptomatic. Diagnosis was incidental in 56.25% with a median lesion size of 25 mm (12-80). Pancreatic resections performed were: pancreatoduodenectomy (31.25%), distal pancreatectomy (56.25%) and total pancreatectomy (12.5%). Median estimated blood loss was 225 mL (15-2,200), median operative time was 242 min (63-420). Median length of stay was 6 days (2-30). New-onset diabetes was 6.25%. The minor complication and reoperation rates, were 37.5% and 6.25%, respectively. The median number of harvested lymph nodes was 17 (4-31), all were negative. All had a R0 resection. Recurrence of disease was 18.75% with a median time after surgery of 3 years (2-6). The median follow up was 9 years (0-15). Thirteen (81.25%) patients are still alive, eight are disease free. Three (18.75%) died. CONCLUSIONS: Long term survival can be achieved with surgical resection of PM from RCC in selected patients in whom complete resection is possible.

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

BACKGROUND: Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS: Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION: Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.

The Increasing Proportion of Early-Stage Pancreatic Cancer between 2004-2013: A SEER Analysis.

Pancreatic cancer will become the second leading cause of cancer-related death in the United States by 2030. Survival improves when it is identified at an early-stage and resected. Increasing public attention and cross-section imaging may shift detection to earlier stages. We found a small total increase in the proportion of stage-I cancer relative to all stages and a significant increase compared to distant disease in the Surveillance, Epidemiology, and End Results (SEER) database. Despite this, our ability to screen and identify early-stage disease is still lacking. Additional research and population-based interventions are necessary to improve early detection.

Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.

BACKGROUND: This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy. METHODS: Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met. RESULTS: In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention. CONCLUSION: In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection. METHODS: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation. RESULTS: 703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent. CONCLUSIONS: This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Technique and audited outcomes of laparoscopic distal pancreatectomy combining the clockwise approach, progressive stepwise compression technique, and staple line reinforcement.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) has proven advantages over its open counterpart and is becoming more frequently performed around the world. It still remains a difficult operation due to the retroperitoneal location of the pancreas and limited experience and training with the procedure. In addition, complications such as bleeding or postoperative pancreatic fistula (POPF) remain a problem. A standardized approach to LDP with stepwise graded compression technique for pancreatic transection has been utilized at a single center, and we sought to describe the technique and determine the outcomes. METHODS: A review of all patients undergoing LDP by a clockwise approach including the graded compression technique from August 1, 2008 to December 31, 2017 was performed. An external audit was performed by the Dutch Pancreatic Cancer Group. RESULTS: Overall, 260 patients with a mean age and a BMI of 62.3 and 28, respectively, underwent LDP using this technique. Mean operative time and blood loss were 183 min and 248 mL, respectively,. Hand-assisted method and conversion to open were both 5%. Major morbidity and mortality were 9.2% and 0.4%, respectively,. POPF was noted in 8.1%. The technical steps include (1) mobilization of the splenic flexure of the colon and exposure of the pancreas, (2) dissection along the inferior edge of the pancreas and choosing the site for pancreatic division, (3) pancreatic parenchymal division using a progressive stepwise compression technique with staple line reinforcement, (4) ligation of the splenic vein and artery, (5) dissection along the superior edge of the pancreas and residual posterior attachments, and (6) mobilization of the spleen and specimen removal. CONCLUSION: LDP with a clockwise approach for dissection, combined with the progressive stepwise compression technique for pancreatic transection, resulted in excellent outcomes including a very low POPF rate.

Physician characteristics associated with treatment initiation patterns in idiopathic pulmonary fibrosis.

Pirfenidone and nintedanib are oral antifibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF). Real-world data on factors that influence IPF treatment decisions are limited. Physician characteristics associated with antifibrotic therapy initiation following an IPF diagnosis were examined in a sample of US pulmonologists. An online, self-administered survey was fielded to pulmonologists between April 10, 2017, and May 17, 2017. Pulmonologists were included if they spent >20% of their time in direct patient care and had ≥5 patients with IPF receiving antifibrotics. Participants answered questions regarding timing and reasons for considering the initiation of antifibrotic therapy after an IPF diagnosis. A total of 169 pulmonologists participated. The majority (81.7%) considered initiating antifibrotic therapy immediately after IPF diagnosis all or most of the time (immediate group), while 18.3% considered it only some of the time or not at all (delayed group). Pulmonologists in the immediate group were more likely to work in private practice (26.1%), have a greater mean percentage of patients receiving antifibrotic therapy (60.8%), and decide to initiate treatment themselves (31.2%) versus those in the delayed group (16.1%, 30.5%, and 16.1%, respectively). Most pulmonologists consider initiating antifibrotic treatment immediately after establishing an IPF diagnosis all or most of the time versus using a "watch-and-wait" approach. Distinguishing characteristics between pulmonologists in the immediate group versus the delayed group included practice setting, percentage of patients receiving antifibrotic therapy, and the decision-making dynamics between the patient and the pulmonologist.

Characterization and Optimal Management of High-risk Pancreatic Anastomoses During Pancreatoduodenectomy.

OBJECTIVE: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.

Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis.

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1) in patients with idiopathic pulmonary fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day-1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs.Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.