Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

BACKGROUND: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

Updated staging and patient outcomes in low-grade appendiceal mucinous neoplasms.

Low-grade appendiceal mucinous neoplasms (LAMNs) exhibit drastically different clinical course and prognosis depending on tumor stage, particularly as it relates to the extent and cellularity of peritoneal involvement. In this context, recent changes in staging guidelines have sought to clarify criteria for pT and pM categories. This study's aim was to identify clinicopathological features associated with patient outcomes, especially as they pertain to updated stage groups. We reviewed LAMNs from 192 patients (mean age: 56.9 years, 119 (62.0%) women). The tumors consisted of 66 (34.4%) pTisM0, 16 (8.3%) pT3M0, 16 (8.3%) pT4aM0, 27 (14.1%) pTxM1a, and 67 (34.9%) pTxM1b cases. In multivariate analysis, only gross perforation was significantly associated with higher TNM group stage (p = 0.001; OR 3.3, 95% CI: 1.7-6.4). Of 165 (85.9%) patients with clinical follow-up, 51 (30.9%) had disease progression (over a mean 33.7 months, range: 4.7-121.7), whereas over significantly longer follow-up (mean 48.7 months, range: 3.1-143.9; p = 0.004), 114 (69.1%) patients did not. In multivariate analysis, higher TNM stage was significantly associated with disease progression (p = 0.029; OR 18.3, 95% CI: 1.4-246.0). In Kaplan-Meier analysis, none of 74 patients with disease limited to the appendix (pM0), 6 of 27 (22.2%) cases with peritoneal involvement by acellular mucin only (pM1a), and 45 of 64 (70.3%) tumors with intraperitoneal deposits containing neoplastic cells (pM1b) showed disease progression (p < 0.001). These differences in progression-free survival among TNM groups persisted when limiting the analysis to patients who had undergone successful cytoreductive surgery (p = 0.050). Finally, in four patients (all with pM1b disease) death was attributed to disease progression whereas there was no disease-specific mortality in the pM0 and pM1a groups (p = 0.020). These data support the designation of LAMNs with acellular peritoneal mucin as having an intermediate prognosis between cases limited to the appendix and those with intraperitoneal deposits containing neoplastic epithelium.

The Safety of Iterative Cytoreductive Surgery and HIPEC for Peritoneal Carcinomatosis: A High Volume Center Prospectively Maintained Database Analysis.

INTRODUCTION: Offering iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal carcinomatosis (PC) poses a surgical dilemma. Safety of this repeated operation in the short and long term has not been largely investigated. METHODS: Patients with PC who underwent 377 CRS/HIPEC procedures between 2007 and 2018 at our institution were included from a prospectively maintained database. Outcomes for patients who had singular CRS/HIPEC were compared with those for patients who had repeated CRS/HIPEC. RESULTS: Overall, there were 325 singular and 52 iterative CRS/HIPEC procedures performed during this time period. Age, sex, and ASA class were comparable between cohorts (p = NS). Optimal cytoreduction, mean operative time, mean length of hospital stay, 90-day major morbidity, and 90-day mortality were also similar. At a median follow-up of 24 months, there was no significant difference in recurrence rate (%, 60 vs 63, p = 0.76), disease-free survival (mean months, 19 vs 15, p = 0.30), and overall survival (mean months, 32 vs 27, p = 0.69). The iterative CRS/HIPEC group had significantly higher rates of major late complications than the singular CRS/HIPEC group (%, 18 vs 40, p < 0.01). CONCLUSION: Repeated CRS/HIPEC for PC has similar perioperative morbidity and mortality, as well as long-term oncological benefits, when compared with singular CRS/HIPEC. However, more than twice as many patients undergoing iterative CRS/HIPEC suffered from major late complications.

Surveillance of Low-Grade Appendiceal Mucinous Neoplasms With Peritoneal Metastases After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Are 5 Years Enough? A Multisite Experience.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMNs) are tumors that often present with widespread mucin in the peritoneal cavity (pseudomyxoma peritonei [PMP]). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment, but no published recommendations exist regarding surveillance. METHODS: Data from prospective databases of patients who underwent CRS-HIPEC from 2001 to 2017 at two high-volume institutions were retrospectively analyzed. Patients who underwent complete CRS-HIPEC for PMP secondary to LAMN were included in the analysis. Pathologic examination confirmed the diagnosis of LAMN. Cases of mucinous adenocarcinomas and neuroendocrine tumors (goblet cell carcinoids) were excluded. RESULTS: The study enrolled 156 patients. The median peritoneal cancer index (PCI) was 18 (interquartile range IQR1-3, 12-23), and 125 patients (80.1%) had a CC0 cytoreduction. According to American Joint Committee on Cancer (AJCC) grading, 152 patients (97.4%) presented with acellular mucin or G1 implants, 2 patients (1.3%) presented with G2 disease, and 2 patients (1.3%) presented with G3 disease. During the follow-up period (median, 45 months; IQR1-3 23-76 months), 23 patients (14.7%) experienced recurrence. All the recurrences were peritoneal and occurred within 5 years. The 1-, 3-, and 5-year disease-free survival (DFS) rates were respectively 95.5%, 83.4%, and 78.3%. Univariate Cox regression analysis showed that higher PCI scores (p < 0.001), a CC1 cytoreduction (p = 0.005), and higher preoperative levels of carcinoembryonic antigen (CEA) (p = 0.012) and CA-125 (p = 0.032) correlated with a shorter DFS. Only higher PCI scores independently predicted earlier recurrences (p < 0.001). CONCLUSION: Most patients had recurrence within 3 years after CRS-HIPEC, and none after 5 years. High PCI was the only independently significant variable. The study findings support intensive surveillance (every 3-6 months) with tumor markers and imaging methods during the first 3 years, and annual surveillance thereafter, with follow-up assessment after 5 years yielding limited benefit.

Correction to: Surveillance of Low-Grade Appendiceal Mucinous Neoplasms With Peritoneal Metastases After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Are 5 Years Enough? A Multisite Experience.

In the original version of the article, Margaret Hofstedt's last name was misspelled.

The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight-institution study of 349 patients over 15 years.

BACKGROUND: Per WHO, 2000 classification, pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma, and are primarily located in the pancreatic body/tail of females. The incidence of MCN and associated malignancy in males, since, standardization of MCN diagnostic-criteria is unknown. METHODS: MCN resections from 2000 to 2014 at eight institutions of the Central-Pancreas-Consortium were included, and divided into early (2000-2007) and late (2008-2014) time-periods. Primary aim was to characterize MCN and associated adenocarcinoma/high-grade-dysplasia (AC/HGD) in males versus females over time. RESULTS: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had MCNs: 310 (89%) female, 39 (11%) male. Patients were equally divided between early (n = 173) and late (n = 176) time-periods. MCN in male-patients decreased over time (early: 15%, late: 7%; P = 0.036), as did pancreatic head/neck location (early: 22%, late: 11%; P = 0.01). MCN-associated AC/HGD was more frequent in males versus females (39 vs. 12%; P < 0.001). The overall rate of MCN-associated AC/HGD remained stable (early: 17%, late: 13%; P = 0.4), and was identical in males (39%) over both time-periods. Males with AC/HGD had more LN-positive disease versus females (57 vs. 22%; P = 0.039). CONCLUSIONS: As the diagnostic-criteria of MCN have standardized over time, MCN diagnosis has decreased in males and head/neck location. Despite this, MCN-associated adenocarcinoma/high-grade dysplasia has been stable and remains high in males. Any male with suspected MCN, regardless of location, should undergo resection.

Who teaches basic procedural skills: student experience versus faculty opinion.

INTRODUCTION: Learning procedural skills as a medical student has evolved, as task trainers and simulators are now ubiquitous. It is yet unclear whether they have supplanted bedside teaching or are adjuncts to it, and whether faculty or residents are responsible for student skills education in this era. In this study we sought to characterize the experience and opinions of both medical students and faculty on procedural skills training. METHODS: Surveys were sent to clinical medical students and faculty at UNC Chapel Hill. Opinions on the ideal learning environment for basic procedural skills, as well as who serves as primary teacher, were gathered using a 4-point Likert scale. Responses were compared via Fisher exact test. RESULTS: A total of 237 students and 279 faculty responded. Third-year students were more likely to report simulation as the primary method of education (64%), compared to either fourth-year students (35%; P < 0.0001) or faculty (43%; P = 0.0018). Third- and fourth-year students were also more likely to report interns as a primary teacher (15% and 10%, respectively) as opposed to faculty (2%), and less likely to suggest faculty were the primary teacher (30% and 21%, respectively, versus 35%), P < 0.0001. Residents were the primary teachers for all three groups (55%, 70%, and 63% respectively). CONCLUSIONS: Our data suggest that both medical students and faculty recognize the utility of simulation in procedural skills training, but vary in the degree to which they think simulation is or should be the primary instructional tool. Both groups suggest residents are the primary teacher of these skills.

African Immigrants in New York City with Hepatitis B-Related Hepatocellular Carcinoma Demonstrate High Morbidity and Mortality.

Guidelines recommend hepatitis B (HBV) testing in individuals from endemic areas, and if positive, screening for hepatocellular carcinoma (HCC). While screening programs are well established in the Asian immigrant population in New York City (NYC), less is known about the characteristics of HBV/HCC among the African immigrant community. A retrospective review was performed of HCC cases from 2005 to 2018 at our institution. Country of origin was not documented in the electronic medical record; therefore, African immigrant status was approximated using self-identified race/ethnicity, positive HBV status, and an online registry to determine country of origin based on last name. Surnames with the greatest prevalence or density in an African country were considered. Among 4400 patients with HCC, 472 identified as non-Hispanic Black; of these, 86 were HBV+. Based on surname, it was estimated that 33 individuals were likely immigrants from Africa. In this group, median age of HCC diagnosis was 48 years (IQR 43-55). In patients with an available date of HBV diagnosis (n = 24), 17 (71%) were unaware of their HBV status when they presented with HCC. Zero patients were diagnosed with HCC through routine screening, most patients (66%) were diagnosed upon imaging evaluation of symptoms. Twelve patients (36%) underwent resection or transplantation; the remaining 64% were ineligible for surgical treatment. Of the 26 patients with follow-up data, 18 (69%) died of disease or were critically ill at last encounter, and of these, 14 (77%) died within 1 year of HCC diagnosis. In conclusion, African immigrants in NYC with HBV/HCC are at high risk of HCC related mortality at a young age. Most were unaware of their hepatitis status at the time of HCC diagnosis. No patients were enrolled in routine HCC screening; the majority were diagnosed based on imaging obtained for symptoms. Most individuals presented with inoperable disease, and the majority died within months of diagnosis. Awareness of these findings may help healthcare providers improve patient outcomes.

Financial burden amongst cancer patients treated with curative intent surgery alone.

BACKGROUND: The costs of cancer care in the US continue to increase and may have serious consequences for patients. We hypothesize that even cancer patients treated with curative-intent surgery alone experience substantial financial burden. METHODS: A questionnaire was administered to adult cancer patients who were treated with curative-intent surgery. Survey items included a validated instrument for measuring financial toxicity, the COST score. Demographic variables and survey responses were examined using Chi-square and Fisher exact tests. A multivariate general linear model was performed to examine the relationship between age and COST score. RESULTS: COST scores varied widely. 30% of respondents had a COST score of ≤24 (high burden). Younger participants reported more financial burden (p = 0.008). Respondents reported that financial factors influenced their decisions regarding surgery (14%) and caused them to skip recommended care (4.7%). Cancer care influenced overall financial health (38%) and contributed to medical debt (26%). CONCLUSION: Curative-intent cancer care places a substantial portion of patients at risk for financial toxicity even when they don't require chemotherapy. Interventions should not be limited to patients receiving chemotherapy.

The Hand-Assisted Laparoscopic Approach to Resection of Pancreatic Mucinous Cystic Neoplasms: An Underused Technique?

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000-2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P = 0.001), lower operative blood loss (192 vs 392 mL; P = 0.001), and shorter hospital stay(5 vs 7 days; P = 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n = 46) had similar advantages as laparoscopic/robotic (n = 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P = 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P = 0.001) and shorter hospital stay (5 vs 7 days; P = 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN.

Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

BACKGROUND & AIMS: While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. METHODS: Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-ß, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. RESULTS: In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. CONCLUSION: Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

Reassessing the cardiac box: A comprehensive evaluation of the relationship between thoracic gunshot wounds and cardiac injury.

BACKGROUND: High-energy missiles can cause cardiac injury regardless of entrance site. This study assesses the adequacy of the anatomic borders of the current "cardiac box" to predict cardiac injury. METHODS: Retrospective autopsy review was performed to identify patients with penetrating torso gunshot wounds (GSWs) 2011 to 2013. Using a circumferential grid system around the thorax, logistic regression analysis was performed to detect differences in rates of cardiac injury from entrance/exit wounds in the "cardiac box" versus the same for entrance/exit wounds outside the box. Analysis was repeated to identify regions to compare risk of cardiac injury between the current cardiac box and other regions of the thorax. RESULTS: Over the study period, 263 patients (89% men; mean age, 34 years; median injuries/person, 2) sustained 735 wounds (80% GSWs), and 239 patients with 620 GSWs were identified for study. Of these, 95 (34%) injured the heart. Of the 257 GSWs entering the cardiac box, 31% caused cardiac injury, whereas 21% GSWs outside the cardiac box (n = 67) penetrated the heart, suggesting that the current "cardiac box" is a poor predictor of cardiac injury relative to the thoracic non-"cardiac box" regions (relative risk [RR], 0.96; p = 0.82). The regions from the anterior to posterior midline of the left thorax provided the highest positive predictive value (41%) with high sensitivity (90%) while minimizing false-positives, making this region the most statistically significant discriminator of cardiac injury (RR, 2.9; p = 0.01). CONCLUSION: For GSWs, the current cardiac box is inadequate to discriminate whether a GSW will cause a cardiac injury. As expected, entrance wounds nearest to the heart are the most likely to result in cardiac injury, but, from a clinical standpoint, it is best to think outside the "box" for GSWs to the thorax. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Factors affecting mortality after penetrating cardiac injuries: 10-year experience at urban level I trauma center.

BACKGROUND: Despite the lethality of injuries to the heart, optimizing factors that impact mortality for victims that do survive to reach the hospital is critical. METHODS: From 2003 to 2012, prehospital data, injury characteristics, and clinical patient factors were analyzed for victims with penetrating cardiac injuries (PCIs) at an urban, level I trauma center. RESULTS: Over the 10-year study, 80 PCI patients survived to reach the hospital. Of the 21 factors analyzed, prehospital cardiopulmonary resuscitation (odds ratio [OR] = 30), scene time greater than 10 minutes (OR = 58), resuscitative thoracotomy (OR = 19), and massive left hemothorax (OR = 15) had the greatest impact on mortality. Cardiac tamponade physiology demonstrated a "protective" effect for survivors to the hospital (OR = .08). CONCLUSIONS: Trauma surgeons can improve mortality after PCI by minimizing time to the operating room for early control of hemorrhage. In PCI patients, tamponade may provide a physiologic advantage (lower mortality) compared to exsanguination.

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study.

Importance: Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN. Objectives: To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma. Design, Setting, and Participants: Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma. Main Outcomes and Measures: Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy. Results: A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years. Conclusions and Relevance: Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.

Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis.

Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.

Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa?

Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors and exhibits the highest mortality rate of any psychiatric disorder. Therapeutic renourishment in AN is founded primarily on clinical opinion and guidelines, with a weak evidence base. Genetic factors do not fully account for the etiology of AN, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from AN. This review explores the relationship between the intestinal microbiota and AN and a potential role for this enteric microbial community as a therapy for this severe illness.

Penetrating cardiac injuries: A 36-year perspective at an urban, Level I trauma center.

BACKGROUND: This study evaluates patterns of injuries and outcomes from penetrating cardiac injuries (PCIs) at Grady Memorial Hospital, an urban, Level I trauma center in Atlanta, Georgia, over 36 years. METHODS: Patients sustaining PCIs were identified from the Trauma Registry of the American College of Surgeons and the Emory Department of Surgery database; data of patients who died prior to any therapy were excluded. Demographics and outcomes were compared over three time intervals: Period 1 (1975-1985; n = 113), Period 2 (1986-1996; n = 79), and Period 3 (2000-2010; n = 79). RESULTS: Two hundred seventy-one patients (86% were male; mean age, 33 years; initial base deficit = -11.3 mEq/L) sustained cardiac stab (SW, 60%) or gunshot wounds (GSW, 40%). Emergency department thoracotomy was performed in 67 (25%) of 271 patients. Overall mortality increased in the modern era (Period 1, 27%, vs. Period 2, 22%, vs. Period 3, 42%; p = 0.03) along with GSW mechanisms (Period 1, 32%, vs. Period 2, 33%, vs. Period 3, 57%; p = 0.001), GSW mortality (Period 1, 36%, vs. Period 2, 42%, vs. Period 3, 56%; p = 0.04), and multichamber injuries (Period 1, 12%, vs. Period 2, 10%, vs. Period 3, 34%; p< 0.001). In Period 3, GSWs (n = 45) resulted in multichamber injuries in 28 patients (62%) and multicavity injuries in 19 patients (42%). Surgeon-performed ultrasound accurately identified pericardial blood in 55 of 55 patients in Period 3. CONCLUSIONS: Increased frequency of GSWs in the past decade is associated with increased overall mortality, multichamber injuries, and multicavity injuries. Ultrasound is sensitive for detection of PCI. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemioligc study, level III.

Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?

BACKGROUND: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. STUDY DESIGN: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. RESULTS: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. CONCLUSIONS: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.