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.

Dissatisfaction after laparoscopic Heller myotomy: The truth is easy to swallow.

BACKGROUND: Although laparoscopic Heller myotomy has been shown to well palliate symptoms of achalasia, we have observed a small subset of patients who are "Dissatisfied". This study was undertaken to identify the causes of their dissatisfaction. STUDY DESIGN: Patients undergoing laparoscopic Heller myotomy from 1992 to 2015 were prospectively followed. Using a Likert scale, patients rated their symptom frequency/severity before and after the procedure. Patients graded their experience from "Very Satisfying" to "Very Unsatisfying." RESULTS: 647 patients underwent laparoscopic Heller myotomy. Fifty (8%) patients, median age 57 years and BMI 24 kg/m2 reported dissatisfaction at follow-up subsequent to myotomy. "Dissatisfied" patients were more likely to have undergone prior abdominal operations (p = 0.01) or previous myotomies (p = 0.02). "Dissatisfied" patients had a greater incidence of diverticulectomy (p = 0.03) and had longer postoperative LOS (p = 0.01). Symptom frequency/severity persisted after myotomy for dissatisfied patients (p > 0.05). CONCLUSION: Dissatisfaction after laparoscopic Heller myotomy is directly related to persistent/recurrent symptoms. Previous abdominal operations/myotomies, diverticulectomies, and longer LOS are predictors of dissatisfaction. With this understanding, we can identify patients who might be more prone to dissatisfaction.

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.

Laparoscopic Spleen-Preserving Total Pancreatectomy for a Main-Duct Intraductal Papillary Mucinous Neoplasm.

INTRODUCTION: Main-duct intraductal papillary mucinous neoplasms of the pancreas (M-IPMN) are potentially malignant cystic neoplasms that can degenerate into invasive malignancy in 43 % of cases.1 Although laparoscopic pancreaticoduodenectomy and distal pancreatectomy have been previously described for the management of pancreatic neoplasms, laparoscopic total pancreatectomy is rarely described. We present a video demonstrating a laparoscopic spleen-preserving total pancreatectomy in a patient with M-IPMN. CASE PRESENTATION: A healthy 66-year-old male was diagnosed with recurrent pancreatitis. A computed tomography of the abdomen demonstrated a diffusely dilated pancreatic duct (10 mm) and a 5 mm mural nodule in the neck of the pancreas. Endoscopic retrograde cholangiopancreatography demonstrated a 'fish mouth' appearance at the major papilla, with a villous mass (15 mm) in the pancreatic head. Biopsy was consistent with M-IPMN, and tumor markers were normal. RESULTS: A spleen-preserving laparoscopic total pancreatectomy was performed over a period of 270 min, with 150 cc of blood loss without complications. The patient was admitted to the intensive care unit for continuous insulin infusion. On postoperative day (POD) 1, his nasogastric tube was discontinued, transitioned to subcutaneous insulin injections, and transferred to the floor. He tolerated a diabetic diet on POD 4. His surgical drain had minimal output with no evidence of a bile leak, and was discontinued on POD 5. The patient's hospital course was uncomplicated and he was discharged home on POD 7. Pathology demonstrated IPMN with moderate dysplasia. CONCLUSION: Laparoscopic total pancreatectomy can be safely performed in patients with M-IPMN. This video presentation describes the technique we used for this procedure.

Molecular profiles in foregut oncology.

Oncology is and will continue to evolve resulting from a better understanding of the biology and intrinsic genetic profile of each cancer. Tumor biomarkers and targeted therapies are the new face of precision medicine, so it is essential for all physicians caring for cancer patients to understand and assist patients in understanding the role and importance of such markers and strategies to target them. This review was initiated in an attempt to identify, characterize, and discuss literature supporting clinically relevant molecular markers and interventions. The efficacy of targeting specific markers will be examined with data from clinical trials focusing on treatments for esophageal, gastric, liver, gallbladder, biliary tract, and pancreatic cancers.

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."

Portal Hypertension Over the Last 25 Years: Where Did It Go?

BACKGROUND: Portal hypertension has seemingly vanished from surgery; this study was undertaken to determine where it has gone. STUDY DESIGN: Data from the Agency for Health Care Administration for 33,166,201 hospital inpatients in Florida for the periods 1988 to 1992, 1998 to 2002, and 2008 to 2012 were analyzed. RESULTS: Admissions with a diagnosis of portal hypertension dramatically increased: 5,473 patients from 1988 to 1992, 7,366 patients from 1998 to 2002, and 36,554 patients from 2008 to 2012. Endoscopic treatment of esophageal varices also dramatically increased. The number of decompressive shunts placed nominally increased, but application of endoscopic therapy increased significantly faster than the application of decompressive shunts (p < 0.0001). The percentage of patients who underwent shunting dramatically and significantly decreased (p < 0.0001), and surgeons undertook proportionally fewer shunts (42% in 1992 to 4% in 2012; p < 0.0001). For patients with a diagnosis of portal hypertension, in-hospital mortality progressively decreased, from 9% in 1988 to 1992 to 3% in 2008 to 2012 (p < 0.0001). CONCLUSIONS: In the state of Florida, over 25 years, there has been a 7-fold increase in the number of patients admitted with a diagnosis of portal hypertension, with a 65% reduction of in-hospital mortality. Application of endoscopic treatment of varices has increased dramatically. Decompressive shunts are applied to an ever-decreasing percentage of patients, and when applied, are now routinely undertaken by nonsurgeons. Therefore, portal hypertension has disappeared from the purview of surgery and has migrated toward the world of medical and endoscopic therapy, probably never to return.

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.