Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats.

BACKGROUND: Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy. METHODS: A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan. RESULTS: We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts. CONCLUSION: PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.

Comparative Outcomes of Anti-Reflux Surgery in Obese Patients with Gastroesophageal Reflux Disease1.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) has been the preferred operation for obese patients with gastroesophageal reflux disease (GERD); however, some patients are hesitant to undergo bypass. Obese patients have a multifactorial predisposition to GERD, including lower esophageal sphincter (LES) dysfunction and aberrant pressure gradients across their diaphragmatic crura. Among non-obese patients, anti-reflux surgery (ARS) with hiatal hernia (HH) repair and LES augmentation has shown excellent long-term results. We aimed to determine whether patient satisfaction and GERD recurrence differed between obese and non-obese patients who underwent ARS. METHODS: Review of patients who underwent ARS between January 2012 and June 2021 was performed. Perioperative and postoperative characteristics were compared across three BMI groups: BMI < 30 kg/m2, 30 kg/m2 ≤ BMI < 35 kg/m2, and BMI ≥ 35 kg/m2. RESULTS: Four-hundred thirteen patients were identified, of which 294 (71.1%) had BMI < 30 kg/m2, 87 (21.1%) were 30 kg/m2 ≤ BMI < 35 kg/m2, and 32 (7.7%) had a BMI ≥ 35 kg/m2. Patients with BMI ≥ 35 kg/m2 had higher preoperative manometric and EndoFLIP™ intra-balloon pressure at the LES than those with lower BMIs. This value was increased to a similar level throughout ARS across the three cohorts. Post-operative GERD-specific satisfaction was similar across the three cohorts, as were rates of postoperative reflux and hiatal hernia recurrence on barium swallow; rates of reoperation were low. CONCLUSIONS: ARS with HH repair and LES augmentation may be appropriate for select patients across a range of BMIs, including those with a BMI ≥ 35 kg/m2 who are hesitant to undergo RYGB.

Quantifying physiologic parameters of the gastroesophageal junction during re-operative anti-reflux surgery.

BACKGROUND: Hiatal hernia re-approximation during index anti-reflux surgery (ARS) contributes approximately 80% of overall change in distensibility index (DI) and, potentially, compliance of the gastroesophageal (GEJ), while sphincter augmentation contributes approximately 20%. Whether this is seen in re-operative ARS is unclear. We quantify the physiologic parameters of the GEJ at each step of robotic re-operative ARS and compare these to index ARS. METHODS: Robotic ARS with hiatal hernia repair was performed on 195 consecutive patients with pathologic reflux utilizing EndoFLIP™, of which 26 previously had ARS. Intra-operative GEJ measurements, including cross-sectional area (CSA), pressure, DI, and high-pressure zone (HPZ) length were collected pre-repair, post-diaphragmatic re-approximation, post-mesh placement, and post-lower-esophageal sphincter (LES) augmentation. RESULTS: Both cohorts were similar by sex and BMI and underwent similar procedures. The re-operative cohort was older (60.6 ± 15.3 vs. 52.7 ± 16.2 years, p = 0.03), had more frequent pre-operative dysphagia (69.2% vs. 42.6%, p = 0.01) and esophageal dysmotility on barium swallow (75.0% vs. 35.0%, p < 0.001) but lower rates of hiatal hernia on endoscopy (30.8% vs. 68.7%, p < 0.001) compared to index procedures. Among the re-operative cohort, the CSA decreased by 34 (IQR - 80, - 15) mm2 and DI 1.1 (IQR - 2.4, - 0.6) mm2/mmHg (both p < 0.001). Pressure increased by 11.2 (IQR 4.7, 14.9) mmHg and HPZ by 1.5 (1,2) cm (both p < 0.001). These changes were similar to those seen in index ARS. Diaphragmatic re-approximation contributed to a greater percentage of overall change to the GEJ than did the augmentation procedure, with 72% of the change in DI occurring during hiatal closure, similar to that seen during index ARS. CONCLUSIONS: During re-operative ARS, dynamic intra-operative monitoring can quantify the effects of each operative step on GEJ physiologic parameters. Diaphragmatic re-approximation appears to have a greater effect on GEJ physiology than does LES-sphincter augmentation during both index and re-operative ARS.

Evaluation of post-operative dysphagia following anti-reflux surgery.

BACKGROUND: Anti-reflux surgery (ARS) has known long-term complications, including dysphagia, bloat, and flatulence, among others. The factors affecting the development of post-operative dysphagia are poorly understood. We investigated the correlation of intra-operative esophagogastric junction (EGJ) characteristics and procedure type with post-operative dysphagia following ARS. METHODS: Robotic ARS was performed on 197 consecutive patients with pathologic reflux utilizing EndoFLIP™ technology. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and high-pressure zone (HPZ) length were collected. Dysphagia was assessed pre-operatively and at 3 months post-operatively. RESULTS: The median pre-operative DI for all procedures was 2.6 (IQR 1.6-4.5) mm2/mmHg. There was no difference in post-operative DI between procedures [Hill: 0.9 (IQR 0.7-1.1) mm2/mmHg, Nissen: 1.0 (IQR 0.7-1.4) mm2/mmHg, Toupet: 1.2 (IQR 0.8-1.5) mm2/mmHg, Linx: 1.0 (IQR 0.7-1.2) mm2/mmHg, p = 0.24], whereas post-operative HPZ length differed by augmentation type [Hill: 3 (IQR 2.8-3) cm, Nissen: 3.5 (IQR 3-3.5) cm, Toupet: 3 (IQR 2.5-3.5) cm, Linx: 2.5 (IQR 2.5-3) cm, p = 0.032]. Eighty-nine patients (45.2%) had pre-operative dysphagia. Thirty-two patients (27.6%) reported any dysphagia at their 3-month post-operative visit and 12 (10.3%) developed new or worsening post-operative dysphagia [Hill: 2/18 (11.1%), Nissen: 2/35 (5.7%), Toupet: 4/54 (7.4%), Linx: 4/9 (44.4%), p = 0.006]. The median pre-operative and post-operative DI of patients who developed new or worsening dysphagia was 2.0 (IQR 0.9-3.8) mm2/mmHg and 1.2 (IQR 1.0-1.8) mm2/mmHg, respectively, and that of those who did not was 2.5 (IQR 1.6-4.0) mm2/mmHg and 1.0 (IQR 0.7-1.4) mm2/mmHg (p = 0.21 and 0.16, respectively). CONCLUSIONS: Post-operative DI was similar between procedures, and there was no correlation with new or worsening post-operative dysphagia. Linx placement was associated with higher rates of new or worsening post-operative dysphagia despite a shorter post-procedure HPZ length and similar post-operative DI when compared to other methods of LES augmentation.

The impact of pneumoperitoneum on esophagogastric junction distensibility during anti-reflux surgery.

OBJECTIVE: We aimed to quantify the contribution of pneumoperitoneum on compliance of the esophagogastric junction (EGJ) during anti-reflux surgery. BACKGROUND: Compliance of the EGJ is reduced with anti-reflux surgery. EndoFLIP® planimetry can be used to assess dynamic changes of EGJ compliance intraoperatively. It is unclear how pneumoperitoneum impacts intraoperative measurements by EndoFLIP® and the implications thereof on validity of the results. Therefore, determining variability in EndoFLIP® measurements based on pneumoperitoneum is warranted to establish guidelines to interpret clinical outcomes. METHODS: Primary anti-reflux surgery was performed on 39 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and intrabag pressure were collected using EndoFLIP® at 0, 10, and 15 mmHg of intraperitoneal pressure. Data were acquired pre-procedure, post-hiatal hernia repair, and post-LES augmentation with fundoplications. RESULTS: Patients underwent Nissen (13.2%), Toupet (68.4%), LINX (10.5%), or Hill-fundoplications (7.9%). There was no difference between 0 and 10 mmHg of pneumoperitoneum in CSA, pressure, or DI measurements pre-procedure; however, there was a difference between 0 and 15 mmHg in pressure (p = 0.016) and DI (p = 0.023) measurements. After LES augmentation, 10 mmHg intraperitoneal pressure reduced DI, though the absolute difference is small (2.0 vs. 1.5 mm2/mmHg, p = 0.002). CONCLUSION: Pneumoperitoneum affected EGJ distensibility at 15 mmHg, but not 10 mmHg, of insufflation prior to anti-reflux procedures. After anti-reflux surgery, there was a significant variance between 0 and 10 mmHg of pneumoperitoneum in pressure and distensibility. The change in pressure appears linear and needs to be considered if procedural modifications are performed based on intraoperative findings and when evaluating clinical outcomes.

ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.

Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry.

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. DISCUSSION: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

Colorectal Cancer Screening in the Elderly.

Colorectal cancer (CRC) is a common and preventable malignancy, and routine CRC screening is recommended for average risk individuals between the ages of 50 and 75 years. Screening has been shown to decrease CRC incidence and mortality. Once patients are older than 75 years, the risk to benefit ratio of ongoing screening begins to shift. As comorbidities increase and life expectancy decreases, the future potential benefits of CRC prevention become less robust, and risk for screening-related complications grows. However, firm age cutoffs are not sufficient to guide these decisions, as there is substantial physiologic heterogeneity among individuals of the same age.

Targeting the Cholecystokinin Receptor: A Novel Approach for Treatment and Prevention of Hepatocellular Cancer.

Hepatocellular carcinoma (HCC) is the fastest growing cancer worldwide in part due to the obesity epidemic and fatty liver disease, particularly nonalcoholic steatohepatitis (NASH). Chronic inflammation with the release of cytokines and chemokines with activation of hepatic stellate cells results in changes of the liver extracellular matrix (ECM) that predisposes to the development of HCC. Blood levels of the gastrointestinal peptide cholecystokinin (CCK) are increased in humans and mice consuming a high-fat diet. We found that the CCK-B receptor (CCK-BR) expression increased in the livers of mice with NASH. Treatment of mice with a CCK-BR antagonist, proglumide, prevented NASH, lowered hepatic inflammatory cytokines and chemokines, reduced oxidative stress, decreased F4/80+ hepatic macrophages, and prevented HCC. CCK-AR and CCK-BR expression was increased in both murine and human HCC cell lines compared with that of normal liver, and CCK stimulated the growth of wild-type and CCK-A receptor knockout HCC cells in vitro, but not CCK-BR knockout cells suggesting that the CCK-BR mediates proliferation. Proglumide therapy significantly reduced growth by 70% and 73% in mice bearing Dt81Hepa1-6 or in RIL-75 HCC tumors, respectively. IHC of a human liver tissue array with a selective CCK-BR antibody revealed staining of human HCC and no staining in normal liver. PREVENTION RELEVANCE: This investigation demonstrates the role of the gastrointestinal peptide cholecystokinin (CCK) in hepatocellular carcinoma (HCC) and how CCK-BR blockade reverses the premalignant state of the hepatic extracellular matrix hence, rendering it less susceptible to the development of HCC. Thereby, CCK-BR blockade is a novel approach for the prevention/treatment of HCC.

Quantifying Factors Essential to the Integrity of the Esophagogastric Junction During Antireflux Procedures.

OBJECTIVE: To quantify the contribution of key steps in antireflux surgery on compliance of the EGJ. BACKGROUND: The lower esophageal sphincter and crural diaphragm constitute the intrinsic and extrinsic sphincters of the EGJ, respectively. Interventions to treat reflux attempt to restore the integrity of the EGJ. However, there are limited data on the relative contribution of critical steps during antireflux procedures to the functional integrity of the EGJ. METHODS: Primary antireflux surgery was performed on 100 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and HPZ length were collected using EndoFLIP. Data was acquired pre-repair, post-diaphragmatic re-approximation with sub-diaphragmatic EGJ relocation, and post-sphincter augmentation. RESULTS: Patients underwent Nissen (45%), Toupet (44%), or LINX (11%). After diaphragmatic re-approximation, DI decreased by a median 0.77 mm2/mm Hg [95%-confidence interval (CI): -0.99, -0.58; P < 0.0001], CSA decreased 16.0 mm2 (95%-CI: -20.0, -8.0; P < 0.0001), whereas HPZ length increased 0.5 cm (95%-CI: 0.5, 1.0; P < 0.0001). After sphincter augmentation, DI decreased 0.14 mm2/mm Hg (95%-CI: -0.30, -0.04; P = 0.0005) and CSA decreased 5.0 mm2 (95%-CI: -10.0, 1.0; P = 0.0.0015), whereas HPZ length increased 0.5 cm (95%-CI: 0.50, 0.54; P < 0.0001). Diaphragmatic re-approximation had a higher percent contribution to distensibility (79% vs 21%), CSA (82% vs 18%), and HPZ (60% vs 40%) than sphincter augmentation. CONCLUSION: Dynamic intraoperative monitoring demonstrates that diaphragmatic re-approximation and sub-diaphragmatic relocation has a greater effect on EGJ compliance than sphincter augmentation. As such, antireflux procedures should address both for optimal improvement of EGJ physiology.

New York Citywide Colon Cancer Control Coalition: A public health effort to increase colon cancer screening and address health disparities.

BACKGROUND: Although screening for colorectal cancer (CRC) is a widely accepted concept nationally and screening rates are increasing, there are differences in screening rates between states and within states. METHODS: In an effort to increase screening rates and ensure equal access with respect to race/ethnicity, the New York City Department of Health and Mental Hygiene formed a coalition of stakeholders in 2003, with its primary focus on colonoscopy, to develop and implement strategies across the city to achieve this goal. RESULTS: From a screening colonoscopy rate of only 42% in 2003, these concerted efforts contributed to achieving a screening rate of 62% by 2007 and a screening rate of almost 70% in 2014 with the elimination of racial and ethnic disparities. CONCLUSIONS: This article provides details of how this program was successfully conceived, implemented, and sustained in the large urban population of New York City. The authors hope that by sharing the many elements involved and the lessons learned, they may help other communities to adapt these experiences to their own environments so that CRC screening rates can be maximized. Cancer 2016;122:269-277. © 2015 American Cancer Society.

Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common human cancers. Recently, emerging evidence has suggested the role of long non-coding RNAs (lncRNAs) in human carcinogenesis. In this study, we aimed to investigate the expression and functional implications of lncRNAs in human HCC. METHODS: Eighty-eight well-annotated lncRNAs were profiled in primary HCC by quantitative RT-PCR. Functional relevance of lncRNAs was elucidated in HCC cell lines and nude mice models. The regulatory relationship between miRNA and lncRNA was predicted in silico and further validated by luciferase reporter assay and expression analysis. RESULTS: In our profiling study, HOTTIP was identified as the most significantly up-regulated lncRNA in human HCCs, even in early stage of HCC formation. Functionally, knock-down of HOTTIP attenuated HCC cell proliferation in vitro and markedly abrogated tumourigenicity in vivo. In addition, knock-down of HOTTIP also inhibited migratory ability of HCC cells and significantly abrogated lung metastasis in orthotopic implantation model in nude mice. HOTTIP is an antisense lncRNA mapped to the distal end of the HOXA gene cluster. Knock-down of HOTTIP significantly suppressed the expression of a number of HOXA genes. Furthermore, we identified miR-125b as a post-transcriptional regulator of HOTTIP. Ectopic expression of miR-125b reduced HOTTIP-coupled luciferase activity and suppressed the endogenous level of HOTTIP. Moreover, in human HCCs, HOTTIP expression negatively correlated with that of miR-125b. CONCLUSIONS: HOTTIP is a novel oncogenic lncRNA, which negatively regulated by miR-125b. Overexpression of HOTTIP contributes to hepatocarcinogenesis by regulating the expression of its neighbouring protein-coding genes.

Prognostic marker microRNA-125b inhibits tumorigenic properties of hepatocellular carcinoma cells via suppressing tumorigenic molecule eIF5A2.

BACKGROUND: MicroRNAs (miRNAs) belong to a group of small non-coding RNA with differential expression in tumors, including hepatocellular carcinoma (HCC). AIM: This study investigates the involvement of miR-125b in HCC. METHODS: Clinical analysis of miR-125b was performed using data derived from miRNA profiling and qPCR. Phenotypic changes of liver cell lines were examined after ectopic miR-125b expression. Lastly, bioinformatics analysis coupled with luciferase reporter assay was used to reveal the cellular target of miR-125b. RESULTS: A down-regulation of miR-125b was found in HCC tumors and cultured cells. Patients having tumors with ≥twofold reduction in miR-125b compared to adjacent non-tumor tissues contributed to 23 out of 49 HCC cases (46.9 %), while this down-regulation was usually found in patients with tumor venous infiltration and recurrence. miR-125b expression was also negatively correlated with increased serum AFP level and poor overall survival of patients. Ectopic expression of miR-125b led to alleviated tumor phenotypes of HCC cells. Among the 110 bioinformatically predicated candidates, 31 of them negatively correlated with miR-125b in HCC tumors for which one of them named eukaryotic translation initiation factor 5A2 (eIF5A2), known also as a liver oncofetal molecule, was validated to be a direct target of miR-125b in HCC. CONCLUSIONS: This study has evidenced for the negative correlation of tumor miR-125b expression with poor prognosis of HCC patients. Expression of miR-125b can reverse the tumorigenic properties of cultured HCC cells via suppressing the tumorigenic molecule eIF5A2, thus postulating restoration of miR-125b level as a way to counteract liver tumorigenesis.

Expression of ankyrin repeat and SOCS box containing 4 (ASB4) confers migration and invasion properties of hepatocellular carcinoma cells.

Ankyrin repeat and SOCS box containing 4 (ASB4) involves in physiological process of ubiquitin-mediated proteasomal degradation. Our previous study demonstrated high expression of ASB4 in hepatocellular carcinoma (HCC) cell lines. This study further reveals its clinical implications and tumorigenic properties in HCC. Analysis of 217 HCC gene expression profiles followed by validation in a separate cohort of 50 cases illustrated high ASB4 in HCC. Among the 50 cases, 54% of tumors exhibited more than 2-fold up-regulation of ASB4. Elevated ASB4 associated with low serum level of a HCC serological marker alpha-fetoprotein (AFP), postulating of its use to differentiate AFP-negative HCC. Suppression of ASB4 in PLC and MHCC97-L HCC cells hindered the cell migration and invasion. Reciprocally, enhanced migration rate was measured when ASB4 was ectopically expressed in Hep3B HCC cells. Cross comparison of results derived from in silico predictions of seed-matched sequences and by analyzing human HCC databases with matched microRNA and gene expression profiles, microRNA-200 (miR-200) family members including miR-200a and miR-200b were predicted to regulate ASB4 expression in HCC. MiR-200a showed inversed expression level with ASB4 in several of studied HCC cell lines. Dual luciferase reporter assay confirmed the presence of miR-200a binding site on the 3' untranslated region of ASB4. Reduced ASB4 level was noticed under the influence of miR-200a mimic treatment, for which this mimic-induced effect was neutralized with miR-200a inhibitor. In conclusion, this study demonstrates for the first time on the involvement of ASB4 in HCC and that its level is regulated by miR-200a.

Reflux and acid peptic diseases in the elderly.

Gastroesophageal reflux disease (GERD) is a common disorder among elderly patients seeking medical care. Diagnosis and management of GERD in the older patient is a unique challenge for both the primary care provider and the gastroenterologist. Such patients may have atypical symptoms, more severe disease, and a higher rate of complications such as erosive esophagitis, Barrett esophagus, and esophageal cancer. Moreover, the elderly may be more sensitive to the morbidity and mortality of the available treatments for GERD. A careful and vigilant approach to the diagnosis, monitoring, and treatment of reflux disease in the elderly is warranted.

Takotsubo cardiomyopathy in chronic infection.

INTRODUCTION: Takotsubo cardiomyopathy is the acquired, reversible syndrome characterised by apical ballooning and base hypercontractility and probably precipitated by emotional and physical stressors that cause a hyperadrenergic state. It presents as an acute coronary event without there being coronary disease. CASE PRESENTATION: We present a case of a 73-year-old woman who developed takotsubo cardiomyopathy with concomitant septic shock from a chronic hemiarthroplasty site infection. The prosthesis had been removed, the surgical site drained twice and multiple antibiotics prescribed. She also had a previous episode of sepsis from she recovered with vasopressor support. CONCLUSION: To the author's knowledge, this is the first case of this syndrome occurring in such a prolonged septic process and where the primary focus was a surgical wound. This may indicate continued myocardial injury secondary to a sustained hyperadrenergic state as a possible mechanism for takotsubo cardiomyopathy, rather than a one-time catecholamine surge.

Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database.

BACKGROUND: The incidence of rectal cancer in the United States in young patients is considered to be low. Underestimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner. METHODS: The authors conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data. A total of 7661 patients with colon, rectal, and rectosigmoid cancer who were diagnosed at age <40 years were identified between 1973 and 2005. The change in incidence over time for colon and rectal/rectosigmoid cancer was calculated and the annual percent change for anatomic subsites of colorectal cancer compared. RESULTS: SEER data demonstrated an increase in the incidence of rectal cancer without any increase in colon cancer (annual percent change of 2.6% vs -0.2%). The difference was statistically significant and extended to rectosigmoid cancer, but not cancer of the sigmoid colon or descending colon (annual percent change of 2.2% vs 0.4% and -2.8%, respectively). Joinpoint analysis of the slope of the curve of rectal and rectosigmoid cancer incidence identified the beginning of the increase to be 1984. All races and both sexes demonstrated similar statistically significant increases in the incidence of rectal and rectosigmoid cancer. CONCLUSIONS: The incidence of rectal and rectosigmoid cancer appears to be increasing in patients aged <40 years. Patients presenting with rectal bleeding or other alarming signs or symptoms should be evaluated with this finding in mind.