Germline CDH1 Variants and Lifetime Cancer Risk.

Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants. Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants. Design, Setting, and Participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022. Main Outcomes and Measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years. Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%). Conclusions and Relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.

Regional differences for pancreaticoduodenectomy in Florida: Location matters.

INTRODUCTION: Regionalization of care raises potential for differences in cost of care and outcome. This study was undertaken to determine if costs and outcome after pancreaticoduodenectomy vary by region in Florida, and whether costs and outcome are related. METHODS: Inpatient data for pancreaticoduodenectomy in Florida during 2010-2012 were obtained from the Florida Agency for Health Care Administration. Seven geographically different regions were designated based on "cost of living index" and "urban to rural population ratio". Hospital costs, LOS, in-hospital mortality, and the frequency with which surgeons performed pancreaticoduodenectomy were evaluated for these regions. RESULTS: Median hospital costs for pancreaticoduodenectomy by region ranged from $101,436-$214,971. Median hospital costs by region correlated positively with LOS (p < 0.0001) and in-hospital mortality (p < 0.0001), and negatively with the frequency of pancreaticoduodenectomies performed by high-volume surgeons (p < 0.0001). CONCLUSIONS: There are regional differences for hospital costs and outcome with pancreaticoduodenectomy in Florida. Regions with lower costs had more pancreaticoduodenectomies performed by high-volume surgeons, shorter LOS, and lower in-hospital mortality rates. Regional differences in cost and quality-of-care need to be studied and abrogated to provide uniform optimal care.

Transthoracic Anastomotic Leak After Esophagectomy: Current Trends.

INTRODUCTION: Leaks from intrathoracic esophagogastric anastomosis are thought to be associated with higher rates of morbidity and mortality than leaks from cervical anastomosis. We challenge this assumption and hypothesize that there is no significant difference in mortality based on the location of the esophagogastric anastomosis. METHODS: A systematic literature search was conducted using PubMed and Embase databases on all studies published from January 2000 to June 2015, comparing transthoracic (TTE) and transhiatal (THE) esophagectomies. Studies using jejunal or colonic interposition were excluded. Outcomes analyzed were leak rate, leak-associated mortality, overall 30-day mortality, and overall morbidity. Meta-analyses were performed using Mantel-Haenszel statistical analyses on studies reporting leak rates of both approaches. Nominal data are presented as frequency and interquartile range (IQR); measures of the association between treatments and outcomes are presented as odds ratio (OR) with 95 % confidence interval. RESULTS: Twenty-one studies (3 randomized controlled trials) were analyzed comprising of 7167 patients (54 % TTE). TTE approach yields a lower anastomotic leak rate (9.8 %; IQR 6.0-12.2 %) than THE (12 %; IQR 11.6-22.1 %; OR 0.56 [0.34-0.92]), without any significant difference in leak associated mortality (7.1 % TTE vs. 4.6 % THE: OR 1.83 [0.39-8.52]). There was no difference in overall 30-day mortality (3.9 % TTE vs. 4.3 % THE; OR 0.86 [0.66-1.13]) and morbidity (59.0 % TTE vs. 66.6 % THE; OR 0.76 [0.37-1.59]). DISCUSSION: Based on meta-analysis, TTE is associated with a lower leak rate and does not result in higher morbidity or mortality than THE. The previously assumed higher rate of transthoracic anastomotic leak-associated mortality is overstated, thus supporting surgeon discretion and other factors to influence the choice of thoracic versus cervical anastomosis.

Financial Benefits of a Hepatopancreaticobiliary Program.

Financial implications of developing a hepatopancreaticobiliary (HPB) center have not been considered. We undertook this study to determine hospital income associated with a new HPB center and to gauge the opportunity cost associated with such a center. Operations included were based on the HPB fellowship curriculum and the six most commonly undertaken general surgery operations. The income with "core" HPB operations (n = 93) and the six most frequently undertaken general surgery operations (n = 583) at one hospital from June 2012 to June 2013 were determined. Patients were not screened based on the ability to pay. Data are reported as mean ± standard deviation. Per operation, hospital income with HPB operations and general surgery operations were $15,583.20 ± $45,909.41 and $5,162.22 ± $33,679.10 (P < 0.005), respectively. Accordingly, net incomes of $1,449,238.04 (n = 93) and $3,009,572.78 (n = 583) were observed. Although general surgery operations are ubiquitous, HPB centers are uncommonly pursued at most hospitals, in part due to the patient volumes necessary to meet the expertise required. A "core" HPB operation produces triple the net income of a general surgery operation. Accordingly, significant financial benefit is achievable with the development of an HPB center when adequate volume is realized.

High-Volume Hospitals with High-Volume and Low-Volume Surgeons: Is There a "Field Effect" for Pancreaticoduodenectomy?

Since the Leapfrog Group established hospital volume criteria for pancreaticoduodenectomy (PD), the importance of surgeon volume versus hospital volume in obtaining superior outcomes has been debated. This study was undertaken to determine whether low-volume surgeons attain the same outcomes after PD as high-volume surgeons at high-volume hospitals. PDs undertaken from 2010 to 2012 were obtained from the Florida Agency for Health Care Administration. High-volume hospitals were identified. Surgeon volumes within were determined; postoperative length of stay (LOS), in-hospital mortality, discharge status, and hospital charges were examined relative to surgeon volume. Six high-volume hospitals were identified. Each hospital had at least one surgeon undertaking ≥ 12 PDs per year and at least one surgeon undertaking < 12 PDs per year. Within these six hospitals, there were 10 "high-volume" surgeons undertaking 714 PDs over the three-year period (average of 24 PDs per surgeon per year), and 33 "low-volume" surgeons undertaking 225 PDs over the three-year period (average of two PDs per surgeon per year). For all surgeons, the frequency with which surgeons undertook PD did not predict LOS, in-hospital mortality, discharge status, or hospital charges. At the six high-volume hospitals examined from 2010 to 2012, low-volume surgeons undertaking PD did not have different patient outcomes from their high-volume counterparts with respect to patient LOS, in-hospital mortality, patient discharge status, or hospital charges. Although the discussion of volume for complex operations has shifted toward surgeon volume, hospital volume must remain part of the discussion as there seems to be a hospital "field effect."

Establishing a framework for building multidisciplinary programs.

While most providers support the concept of a multidisciplinary approach to patient care, challenges exist to the implementation of successful multidisciplinary clinical programs. As patients become more knowledgeable about their disease through research on the Internet, they seek hospital programs that offer multidisciplinary care. At the University of Colorado Hospital, we utilize a formal multidisciplinary approach across a variety of clinical settings, which has been beneficial to patients, providers, and the hospital. We present a reproducible framework to be used as a guide to develop a successful multidisciplinary program.

Long-term Outcomes Favor Duodenum-preserving Pancreatic Head Resection over Pylorus-preserving Pancreaticoduodenectomy for Chronic Pancreatitis: A Meta-analysis and Systematic Review.

Pylorus-preserving pancreaticoduodenectomy (PPPD) and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. This meta-analysis was undertaken to compare the long-term outcomes of DPPHR versus PPPD in patients with chronic pancreatitis. A systematic literature search was conducted using Embase, MEDLINE, Cochrane, and PubMed databases on all studies published between January 1991 and January 2013 reporting intermediate and long-term outcomes after DPPHR and PPPD for chronic pancreatitis. Long-term outcomes of interest were complete pain relief, quality of life, professional rehabilitation, exocrine insufficiency, and endocrine insufficiency. Other outcomes of interest included perioperative morbidity and length of stay (LOS). Ten studies were included comprising of 569 patients. There was no significant difference in complete pain relief (P = 0.24), endocrine insufficiency (P = 0.15), and perioperative morbidity (P = 0.13) between DPPHR and PPPD. However, quality of life (P < 0.00001), professional rehabilitation (P = 0.004), exocrine insufficiency (P = 0.005), and LOS (P = 0.00001) were significantly better for patients undergoing DPPHR compared with PPPD. In conclusion, there is no significant difference in endocrine insufficiency, postoperative pain relief, and perioperative morbidity for patients undergoing DPPHR versus PPPD. Improved intermediate and long-term outcomes including LOS, quality of life, professional rehabilitation, and preservation of exocrine function make DPPHR a more favorable approach than PPPD for patients with chronic pancreatitis.

Pancreaticoduodenectomy in Florida: do 20-year trends document the salutary benefits of centralization of care?

BACKGROUND: Concentration of care has been promoted as fostering superior outcomes. This study was undertaken to determine if the concentration of care is occurring in Florida for a pancreaticoduodenectomy, and if so, is it having a salutary effect. METHODS: The data for a pancreaticoduodenectomy were obtained from the Florida Agency for Health Care Administration for three 3-year periods:1992-1994, 2001-2003, 2010-2012; data were sorted by surgeon volume of pancreaticoduodenectomy during these periods and correlated with post-operative length of stay (LOS), in-hospital mortality and hospital charges (adjusted to 2012 dollars). RESULTS: Relative to 1992-1994, in 2010-2012 46% fewer surgeons performed 115% more pancreaticoduodenectomies with significant reductions in LOS and in-hospital mortality, and higher charges (P < 0.001 for each). From 1992-1994 to 2010-2012 there was an 18-fold increase in the number of pancreaticoduodenectomies by surgeons completing ≥ 12 per year (n = 45 to n = 806, respectively). During 2010-2012, the more frequently surgeons performed a pancreaticoduodenectomy, the shorter LOS, the lower in-hospital mortality, the greater the likelihood of discharge home and the lower the hospital charges (P < 0.03 for each). CONCLUSIONS: Over the last 20 years, the concentration of care has occurred in Florida with substantially fewer surgeons undertaking many more pancreaticoduodenectomies with dramatic improvements in LOS and in-hospital mortality, albeit with increased hospital charges.

Reoperative Heller myotomy: more pain, less gain.

Heller myotomy provides durable and effective treatment of achalasia. Due to recurrence or persistence of symptoms, a small subset of patients seeks reoperation. This study was undertaken to determine if reoperative Heller myotomy provides salutary amelioration of symptoms. 609 patients undergoing laparoscopic Heller myotomy between 1992 to 2013 were prospectively followed; 38 underwent reoperative myotomy. Patients graded their symptom frequency and severity before and after myotomy on a Likert scale. Median data are reported. Patients undergoing reoperative myotomy, when compared to those undergoing their first myotomy, experienced a higher conversion rate to an "open" myotomy (8% vs 1%, P < 0.05) and a longer length of stay (3 vs 1 day, P < 0.05). Reoperative myotomy led to improvement in symptoms, but the magnitude of improvement in symptoms (e.g., dysphagia, choking, and coughing) was less than for patients undergoing their first myotomy (all P < 0.05). Patients undergoing reoperative Heller myotomy were less likely to report symptoms occurring once per month or less (83% vs 56%, P < 0.01). Patients undergoing reoperative myotomy note improvement in symptoms, although to a lesser extent than patients undergoing their first myotomy. Patients undergoing reoperative Heller myotomy can expect to experience less improvement of symptoms, denoting the importance of the first myotomy.

Distal pancreatectomy and splenectomy: a robotic or LESS approach.

INTRODUCTION: The role and application of robotic surgery are debated, particularly given the expansion of laparoscopy, especially laparoendoscopic single-site (LESS) surgery. This cohort study was undertaken to delineate differences in outcomes between LESS and robotic distal pancreatectomy and splenectomy. METHODS: With Institutional Review Board approval, patients undergoing LESS or robotic distal pancreatectomy and splenectomy from September 1, 2012, through December 31, 2014, were prospectively observed, and data were collected. The results are expressed as the median, with the mean ± SD. RESULTS: Thirty-four patients underwent a minimally invasive distal pancreatectomy and splenectomy: 18 with robotic and 16 with LESS surgery. The patients were similar in sex, age, and body mass index. Conversions to open surgery and estimated blood loss were similar. There were two intraoperative complications in the group that underwent the robotic approach. Time spent in the operating room was significantly longer with the robot (297 vs 254 minutes, P = .03), although operative duration (i.e., incision to closure) was not longer (225 vs 190 minutes; P = .15). Of the operations studied, 79% were undertaken for neoplastic processes. Tumor size was 3.5 cm for both approaches; R0 resections were achieved in all patients. Length of stay was similar in the two study groups (5 vs 4 days). There was one 30-day readmission after robotic surgery. CONCLUSIONS: Patient outcomes are similar with LESS or robotic distal pancreatectomy and splenectomy. Robotic operations require more time in the operating room. Both are safe and efficacious minimally invasive operations that follow similar oncologic principles for similar tumors, and both should be in the surgeon's armamentarium for distal pancreatectomy and splenectomy.