Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention and control of peritoneal metastasis in patients with gastrointestinal malignancies: a systematic review of randomized controlled trials.

Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis.

Aberrant Partial Chromosomal Instability With Chemotherapeutically Resistant Metachronous Colorectal Cancer Following a Synchronous Primary Colorectal Cancer: A Case Report.

The diagnosis of synchronous colorectal cancer (CRC) is crucial as the management, including the extent of surgical resection, depends on it. There have been numerous studies on the clinicopathological features of synchronous CRC; however, only a few studies have discussed synchronous cancer treatment. The guidelines to best manage the synchronous and metachronous CRC are limited, especially the most appropriate surgical treatment and chemotherapy based on mutational analysis of mismatch repair genes and the carcinoma sequence model. We present a rare case of a metachronous CRC with intact nuclear expression of microsatellite instability markers following a synchronous CRC, and it failed to show any significant response to surgical resection and chemoradiotherapy. A 53-year-old female presented in June 2016 with bleeding per rectum for one month, weight loss, and a recent history of altered bowel habits. The per rectal examination revealed a circumferential growth. Colonoscopy and biopsy yielded multiple polyps throughout the colon and invasive adenocarcinoma in the upper and lower one-third of the rectum. The above features were highly suggestive of synchronous CRC. Serologic studies revealed elevated carcinoembryonic antigen (CEA). Excisional biopsy of mesenteric and retroperitoneal lymph nodes during proctocolectomy and end ileostomy was negative for metastasis, including the other metastatic workup preoperatively-eight months post-resection and adjuvant chemotherapy patient developed metachronous CRC. Mutational analysis showed positivity only for adenomatous polyposis coli (APC) while negative for KRAS, NRAS, and BRAF. Immunohistochemistry (IHC) markers for mismatch repair (MMR) proteins showed intact protein expression. The patient was given multiple chemotherapy cycles throughout her course, including oral capecitabine, XELOX (capecitabine + oxaliplatin), cetuximab-capecitabine, cetuximab-irinotecan, and FOLFIRI (5-fluorouracil [5-FU] + irinotecan + folinic acid)-bevacizumab, as is the standard chemotherapy regimen for these tumors. The diagnosis of metachronous CRC with intensive follow up is crucial. IHC markers for MMR proteins showed intact protein expression ruling out the possibility of microsatellite instability and Lynch Syndrome. The only presence of APC mutation indicates a partial chromosomal instability. During the course, the patient had either stable size of the masses or developed new metastatic growth despite intensive chemotherapeutic regimes. Unfortunately, there are no precise guidelines based on aberrant mutational analysis regarding synchronous and metachronous CRCs management.

Is Emergency Appendicectomy Better Than Elective Appendicectomy for the Treatment of Appendiceal Phlegmon?: A Review.

Appendiceal phlegmon is considered to be sequelae to acute appendicitis which presents as an appendiceal mass composed of the inflamed appendix, the adjacent bowel loops, and the greater omentum. The definitive diagnosis can be obtained by a CT scan of the abdomen. Though conservative management was the most practiced approach, recent studies have shifted the trends towards immediate appendicectomy for the management of appendiceal phlegmon. Thus, the management of appendiceal phlegmon has been debatable. Evidence to support this review was gathered via the PubMed database as this database uses the Medline, PubMed Central, and NLM databases and also offers a quick diverse search with up-to-date citations and numerous open-access free articles focused on Medicine. We did not include other databases like Google Scholar, Embase, and Scopus due to its limited access to free articles, recent articles, and citation information. Search terms used were combinations of "Appendicitis," "Appendiceal phlegmon", "Appendiceal phlegmon (AND) appendicectomy ". The resultant studies were reviewed and cross-referenced for additional reports. Emergency appendicectomy is defined as appendicectomy carried out during the same, initial admission. An elective or interval appendicectomy is an appendicectomy carried out four to six weeks after the initial episode at a later admission. The interval is bridged by antibiotics and conservative management. Emergency appendicectomy is considered to have a higher rate of complications when compared to conservative management for appendiceal phlegmon. However, interval appendicectomy requires multiple re-admissions, leads to delayed diagnosis of any underlying pathology, and an increased risk of recurrent appendicitis. In our review, we aimed to compare and contrast the effectiveness of the different treatment modalities available for appendiceal phlegmon. Though the meta-analyses showed an increased association of complications with emergency appendicectomy, they included studies conducted before the laparoscopic era. Emergency appendicectomy decreases the financial burden, re-admission rate, and aids in the early diagnosis of any underlying pathology. In the laparoscopic era, we can consider the shifting trends towards emergency appendicectomy for the management of appendiceal phlegmon.

Comparison of the Efficacy of the Various Treatment Modalities in the Management of Perianal Crohn's Fistula: A Review.

Crohn's disease (CD) is a transmural inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal (GI) tract. With the disease's progression, adhesions and transmural fissuring, intra-abdominal abscesses, and fistula tracts may develop. An anal fistula (or fistula-in-ano) is a chronic abnormal epithelial lined tract communicating the anorectal lumen (internal opening) to the perineal or buttock skin (external opening). The risk of fistula development varies from 14%-38%. It can cause significant morbidity, which adversely impacts the quality of life. It is mostly believed that an anal crypt gland infection causes anal abscesses, leading to fistula development. Crohn's disease's pathogenesis involves Th1 and Th17 hypersensitivity due to an unknown antigen within the intestinal mucosa. Evidence to support this review was gathered via the Pubmed database. Search terms used were combinations of "Perianal fistula," "seton," "immunotherapy." Studies were reviewed and cross-referenced for additional reports. Setons are surgical thread loops passed from the external to the internal opening of the fistula tract and exteriorized through the anorectal canal, facilitating abscess drainage and inciting a local inflammatory reaction, thus promoting the resolution of the fistula. Biologicals such as anti-tumor necrosis factor (TNF) antibody (infliximab, adalimumab, certolizumab), anti-IL-12/23 (ustekinumab), and anti-α4ß7 integrin antibody (vedolizumab) have been approved for Crohn's disease targeting the Th1/Th17-mediated inflammation. Other therapeutic modalities are fistulotomy, cyanoacrylate glue, bioprosthetic plugs, mucosal advancement flap, ligation of inter-sphincteric fistula tract (LIFT), diverting stoma, proctectomy, video-assisted anal fistula treatment (VAAFT), and fistula laser closure (FiLaC). Our review found that chronic seton therapy should be the primary approach, especially if the patient has a perianal abscess. It has a low incidence of re-intervention, recurrent abscess formation, and side-branching of the fistulous tract, with preservation of the fistulous tract's patency and cost-effectiveness. The major disadvantage of seton therapy is the discomfort and time to achieve stability. Among the biologicals, infliximab is the only therapy which has a statistically significant effect on the healing rate of perianal Crohn's fistula compared to placebo, but the major disadvantage associated with anti-TNF as sole therapy is high re-intervention rate, prolong maintenance therapy, high recurrence rate, and severe side effects. We hypothesize that the two aspects should be addressed concurrently to increase the fistula healing or closure rate. First, the seton should be used as initial therapy to maintain tract patency to allow abscess drainage and minimize the intestinal flora colonization within the tract mucosa, thereby leukocytic infiltration and propagation of inflammation within the tract. The second aspect that has to be considered is that we should target the initial stimulation of the Th1/Th17 mediated hypersensitivity instead of a factor/cytokine involved in the inflammation mediation. Although the unknown antigen triggering such hypersensitivity is not clear, we could target the RAR-related orphan receptor γ (RORγ)-T (transcription factor involved in activation of Th17 cells) and the T-bet (transcription factor involved in activation of Th17 cells) within the GI mucosa by a novel target immune therapy.

National disparities in minimally invasive surgery for pancreatic tumors.

BACKGROUND: For patients with pancreatic tumors, several disparities have been shown to impact access to care, including surgery, and subsequently adversely affect long-term oncologic outcomes. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS) across different demographics for pancreatic tumors. METHODS: We utilized the American College of Surgeons (ACS) National Cancer Data Base (NCDB) to identify patients with pancreatic tumors from 2010 to 2011 who had undergone surgery through either an open or MIS approach. Multivariable analysis was performed to investigate differences in patient characteristics in relation to surgical approach and conversion to open. RESULTS: A total of 2809 patients were identified. The initial surgical approach included 86.5 % open (2430) and 13.5 % MIS (87.6 % were laparoscopic, and 12.4 % were robotic). Tumor histology was significantly associated with MIS, whereby patients with neuroendocrine tumors were more than twice as likely to have an MIS approach compared to adenocarcinoma. Tumor location within the pancreas was also associated with MIS, with tumors in the tail being three times more likely to be removed through MIS compared to tumors in the head. For patients with disease in the body or tail of the pancreas, ethnicity was independently associated with MIS whereby patients of Hispanic origin were less likely to have MIS. The conversion rate to open was 27.7 %, and geographic location was associated with conversion rates. CONCLUSIONS: MIS procedures comprise approximately 13.5 % of surgical procedures for pancreatic tumors. In addition to tumor histology, differences in surgical approach were identified with respect to ethnicity for patients with tumors in the body/tail of the pancreas.

Preoperative Assessment and Optimization of the Future Liver Remnant.

Liver resection of benign, primary, and metastatic tumors is challenging and places patients at risk for postoperative liver insufficiency. The magnitude of this risk largely depends on the volume and function of the future liver remnant (FLR). It is, therefore, critical that hepatobiliary surgeons are well versed in measurement of liver volume and function as well as various techniques for preoperative liver volume augmentation. The absolute volume of FLR required to avoid postoperative liver insufficiency depends on patient, disease, and anatomic factors. Rapid expansion of the FLR can safely be achieved with portal venous embolization of the contralateral liver segments.

Predicting Individualized Postoperative Survival for Stage II/III Colon Cancer Using a Mobile Application Derived from the National Cancer Data Base.

BACKGROUND: Prediction calculators estimate postoperative survival and assist the decision-making process for adjuvant treatment. The objective of this study was to create a postoperative overall survival (OS) calculator for patients with stage II/III colon cancer. Factors that influence OS, including comorbidity and postoperative variables, were included. STUDY DESIGN: The National Cancer Data Base was queried for patients with stage II/III colon cancer, diagnosed between 2004 and 2006, who had surgical resection. Patients were randomly divided to a testing (nt) cohort comprising 80% of the dataset and a validation (nv) cohort comprising 20%. Multivariable Cox proportional hazards regression of nt was performed to identify factors associated with 5-year OS. These were used to build a prediction model. The performance was assessed using the nv cohort and translated into mobile software. RESULTS: A total of 129,040 patients had surgery. After exclusion of patients with carcinoma in situ, nonadenocarcinoma histology, more than 1 malignancy, stage I or IV disease, or missing data, 34,176 patients were used in the development of the calculator. Independent predictors of OS included patient-specific characteristics, pathologic factors, and treatment options, including type of surgery and adjuvant therapy. Length of postoperative stay and unplanned readmission rates were also incorporated as surrogates for postoperative complications (1-day increase in postoperative stay, hazard ratio [HR] 1.019, 95% CI 1.018 to 1.021, p < 0.001; unplanned readmission vs no readmission HR 1.35, 95% CI 1.25 to 1.45, p < 0.001). Predicted and actual 5-year OS rates were compared in the nv cohort with 5-year area under the curve of 0.77. CONCLUSIONS: An individualized, postoperative OS calculator application was developed for patients with stage II/III colon cancer. This prediction model uses nationwide data, culminating in a highly comprehensive, clinically useful tool.

Nationwide analysis of short-term surgical outcomes of minimally invasive esophagectomy for malignancy.

BACKGROUND: Minimally invasive esophagectomy (MIE) is being increasingly utilized for esophageal cancer. It is unclear if MIE if being safely performed with satisfactory outcomes across the USA. We aimed to analyze the short-term surgical outcomes of MIE as compared to open esophagectomy (OE). METHODS: The National Cancer Database (NCDB) was queried for patients who underwent MIE or OE for esophageal malignancy between 2010 and 2011. Margin positivity, lymph node retrieval, 30-day mortality, 30-day unplanned readmission rate and hospital length of stay. RESULTS: A total of 4047 patients were identified; 3050 (75.4%) underwent OE, and 997 (24.6%) underwent MIE. The proportion of MIE increased from 21.9% in 2010 to 27.4% in 2011 (p < 0.001). The conversion rate was 13.7%. There were no differences in-patient or tumor characteristics between the two cohorts. OE and MIE were comparable in terms of margin positive resection rate (7.4% vs. 8.1%, p = 0.48), 30-day unplanned readmission rate (7.6% vs. 7.2%, p = 0.64) and 30-day mortality rate (4.3% vs. 3.3%, p = 0.71). Compared to OE, MIE was associated with higher node retrieval (median 12 vs 14, p < 0.001), and shorter hospital stay (median 11.0 vs 10.0 days, p < 0.001). Logistic regression analysis showed that surgical approach (OE vs MIE) was not associated with 30-day mortality rate. In an ANCOVA analysis, MIE was independently associated with a shorter hospital stay compared to OE (estimated mean difference 1.57 ± 0.53 days, p = 0.003). MIE patients who underwent conversion had a longer hospital stay compared to those who did not (11.0 vs 10.0 days, p = 0.02). CONCLUSION: MIE is being offered more frequently to patients with esophageal cancer, and maybe accompanied with better short-term outcomes including shorter hospital stay when compared to open esophagectomy.

National disparities in minimally invasive surgery for rectal cancer.

BACKGROUND: Social and racial disparities have been identified as factors contributing to differences in access to care and oncologic outcomes in patients with colorectal cancer. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS), both laparoscopic and robotic, across different racial, socioeconomic and geographic populations of patients with rectal cancer. METHODS: We utilized the American College of Surgeons National Cancer Database to identify patients with rectal cancer from 2004 to 2011 who had undergone definitive surgical procedures through either an open, laparoscopic or robotic approach. Inclusion criteria included only one malignancy and no adjuvant therapy. Multivariate analysis was performed to investigate differences in age, gender, race, income, education, insurance coverage, geographic setting and hospital type in relation to the surgical approach. RESULTS: A total of 8633 patients were identified. The initial surgical approach included 46.5% open (4016), 50.9% laparoscopic (4393) and 2.6% robotic (224). In evaluating type of insurance coverage, patients with private insurance were most likely to undergo laparoscopic surgery [OR (odds ratio) 1.637, 95% CI 1.178-2.275], although there was a less statistically significant association with robotic surgery (OR 2.167, 95% CI 0.663-7.087). Patients who had incomes greater than $46,000 and received treatment at an academic center were more likely to undergo MIS (either laparoscopic or robotic). Race, education and geographic setting were not statistically significant characteristics for surgical approach in patients with rectal cancer. CONCLUSIONS: Minimally invasive approaches for rectal cancer comprise approximately 53% of surgical procedures in patients not treated with adjuvant therapy. Robotics is associated with patients who have higher incomes and private insurance and undergo surgery in academic centers.

National Disparities in Surgical Approach to T1 Rectal Cancer and Impact on Outcomes.

This study investigated disparities between patients who had local excision versus radical resection for T1 rectal cancer. A retrospective analysis was performed using the National Cancer Data Base, 2004 to 2011. Inclusion criteria consisted of patients with T1, N0 rectal adenocarcinoma that were <3 cm, well or moderately differentiated without perineural invasion. Patients were stratified based on local excision and radical surgery. The primary outcome was overall survival (OS). Secondary outcomes included 30-day mortality, unplanned readmission rates, and postoperative length of stay. A total of 2235 patients were identified; 1335 (59.7%) underwent local excision and 900 (40.3%) had radical surgery. Overall, radical surgery was associated with an improved 5-year OS rate compared to local excision (0.86 vs 0.78, P = 0.009), increased unplanned readmission (6.5% vs 2.7%, P < 0.001), and longer postoperative length of stay (6.9 days vs 3.1 days, P < 0.001). For patients who had local excision, insurance status was an independent predictor of OS. Compared to patients with private insurance, those with government plans or no insurance had poorer OS (hazard ratio = 1.77 and 17.45, respectively, P = 0.006). Further study is warranted to understand the reasons accounting for this disparity in surgical approach to T1 rectal cancer.

Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival.

IMPORTANCE: The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) levels (C stage) into the conventional TNM staging system of colon cancer. The latter proposal has yet to be widely adopted because of the lack of long-term survival estimates of after C-stage incorporation into AJCC staging. OBJECTIVES: To evaluate whether long-term overall and cancer-specific survival is affected by inclusion of C stage into the standard AJCC TNM staging and to study the implications on survival estimates. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective study of all patients diagnosed as having histologically proven colonic adenocarcinoma from January 1, 2004, through December 31, 2005, from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We stratified each AJCC stage as C0 (normal) or C1 (elevated) based on the pretreatment serum CEA level. Median follow-up was 71 months. MAIN OUTCOME AND MEASURES: Five-year estimates of overall and disease-specific survival and hazard ratios (HRs) for estimates of risk of overall and disease-specific mortality. RESULTS: A total of 16 619 patients were evaluated, and of these, 8878 patients had C0 disease and 7741 had C1 disease. C1 stage was independently associated with a 51% and 59% increased risk of overall (HR, 1.51; 95% CI, 1.44-1.59; P < .001) and disease-specific mortality (HR, 1.59; 95% CI, 1.49-1.69; P < . 001) at a median follow-up of 71 months. Analysis of survival of the AJCC stages subdivided as C0 or C1 revealed a significant worse prognosis of C1 AJCC stages compared with the respective C0 AJCC stages. The magnitude of change in survival was large enough to cause clustering of survival estimates of C1 vs C0 cancers across various AJCC stages. Analysis of patients with stage I, II, and III cancer revealed that node-negative C1 disease was associated with prognosis similar or worse than node-positive C0 disease. CONCLUSIONS AND RELEVANCE: Inclusion of C stage into the AJCC TNM staging of colon cancer revealed significant differences dependent on C stage in terms of 5-year survival. C-stage inclusion resulted in substantial change in survival estimates, with C1 status portending a prognosis to certain stages similar to or worse than higher AJCC TNM stages with C0 status. We recommend routine pretreatment CEA testing as standard of care in colon cancer and use of C stage for multimodality treatment planning and risk stratification in prospective studies and randomized clinical trials.

Pre-operative unintentional weight loss as a risk factor for surgical outcomes after elective surgery in patients with disseminated cancer.

BACKGROUND: With improvement in survival, elective surgical procedures are being increasingly performed on patients with metastatic disease. We aimed to study the association of pre-operative unintentional weight loss (UWL) with operative outcomes in this patient population. METHODS: We extracted data on all patients with disseminated cancer undergoing elective surgeries between 2005 and 2011 from the National Surgical Quality Improvement Program (NSQIP), along with the Current Procedure Terminology (CPT) codes. Based on the presence of unintentional weight loss of >10% body weight in the 6-month period preceding surgery, patients were divided into 2 cohorts - (1) patients with UWL ('UWL' cohort) and (2) patients without UWL ('No UWL') cohort. Differences in patient characteristics, co-morbid conditions and outcomes were compared. RESULTS: There were 30,669 surgeries recorded under 1,638 CPT codes, with 8,436 surgeries involving the eight most common CPT codes. UWL was present in 11.5% of all patients. UWL patients were more commonly (P < 0.05) male, African-American, of higher ASA (American Society of Anesthesiology) class, and had multiple associated comorbidities. Nearly all complications, including wound infections, prolonged ventilator requirement, unplanned intubation, cardiac arrest, DVT, sepsis and mortality were more common in UWL patients. Multivariate analysis demonstrated that UWL was independently associated with 21%, 22% and 49% higher risk of overall morbidity, serious morbidity and 30-day mortality, respectively. CONCLUSION: UWL is an independent risk factor associated with increased morbidity and mortality following elective surgeries in patients with disseminated cancer.

A rationally designed A34R mutant oncolytic poxvirus: improved efficacy in peritoneal carcinomatosis.

Oncolytic poxviruses have demonstrated initial promising results in patients with cancer in clinical trials, yet further improvements are needed. It has been shown that a single point mutation in the A34R gene resulted in the production of more total progeny virus and more extracellular enveloped virus (EEV), a form that can be immune-evasive and with enhanced spread. We have genetically engineered a new oncolytic poxvirus (designated vA34R) by incorporating this mutated A34R gene into a viral backbone (vvDD) which was designed for tumor-selective replication. This rationally designed virus can evade neutralization from antipoxvirus antibodies and is highly cytotoxic to cancer cells. It demonstrates improved spread and increased replication within the peritoneal cavity resulting in improved antitumor effects in a peritoneal carcinomatosis (PC) model of MC38 colon cancer. Impressively, after carrier cell-mediated delivery in the preimmunized host, vA34R displayed high replication in tumor nodules yet low accumulation in normal tissues thus enhancing the therapeutic index leading to 70% long-term cures. These results demonstrate that vA34R gains an enhanced therapeutic index for PC via immune evasion, increased spread, and production of more progeny virus. Thus, vA34R may be a potent oncolytic virus (OV) for patients with PC, even after prior exposure to vaccinia virus (VV).

C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management.

BACKGROUND: The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. METHODS: Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. RESULTS: C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). CONCLUSIONS: C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

Meckel's diverticulum--a high-risk region for malignancy in the ileum. Insights from a population-based epidemiological study and implications in surgical management.

BACKGROUND: Surgical management of incidental Meckel's diverticulum(MD) is a highly debated controversial issue that has never been discussed from the oncological standpoint. OBJECTIVE: To describe the epidemiology and risk of Meckel's diverticulum cancer (MDC) and compare it with other ileal malignancies. METHODS: Data were obtained from 163 cases of MDC and 6214 cases of non-Meckelian ileal cancer, between 1973 and 2006, from the Surveillance, Epidemiology, and End Results database. RESULTS: Mean annual incidence was 1.44 (± 1.12) per 10 million population,with a 5-fold increase in the last few decades. Incidence increases with age,with a mean age at diagnosis of 60.6 (±15.1) years. Adjusted risk of cancer in the MD was at least 70 times higher than any other ileal site. Disease was localized in 67% at presentation and malignant carcinoids constituted the major histologic type (77%). One-third of patients have had lifetime occurrence of other malignancies and in 13% of these patients, MDC was the first malignancy. Median tumor size was 7 mm. Median overall survival was 173 months (95% confidence interval [CI], 124-221 months), with 1- and 5-year relative survival rates of 85.8% (95% CI, 76.9%-91.4%) and 75.8% (95%CI, 64.9%-83.8%), respectively. Cox proportional hazards model revealed that age, histologic type, and metastatic disease were independent factors affecting survival. CONCLUSIONS: MD is a "hot-spot" or high-risk area for cancer in the ileum.With risk that increases with age and high possibility of curative resection with negligible operative mortality, incidental MD is best treated with resection.

Educational intervention is effective in improving knowledge and confidence in surgical ethics-a prospective study.

BACKGROUND: Professionalism and ethics are Accreditation Council for Graduate Medical Education (ACGME) core competencies, but there is little evidence regarding the effectiveness of ethics education. METHODS: General surgery residents at the University of Pittsburgh completed questionnaires measuring attitudes and knowledge about surgical ethics before and after four 60-minute, faculty-facilitated seminars implementing the American College of Surgeons ethics curriculum. RESULTS: Most residents experienced ethical challenges at least once every rotation: competition of interests (75%), professional obligations (75%), confidentiality (83%), truth telling (88%), surrogate decision making (91%), and end-of-life issues (100%). The educational intervention increased both knowledge about surgical ethics (P = .013) and confidence in dealing with competition of interests (P = .001), professional obligations (P = .011), truth telling (P = .013), confidentiality (P = .011), end-of-life issues (P = .007), and surrogate decision making (P = .052). Most residents recommended the American College of Surgeons text for future use (84%), considering ethics education a "standard" part of residency training (70%). CONCLUSIONS: Focused instruction using the American College of Surgeons ethics curriculum can effectively improve both knowledge and confidence about surgical ethics.

Medullary carcinoma of the large intestine: a population based analysis.

Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.