ABSTRACT
We present a rare case of thrombosis associated with an occult colon malignancy (Trousseau syndrome) in a 25-year-old woman who also presented with previously unidentified Lynch syndrome and acute-on-chronic thromboembolic pulmonary hypertension. Staged treatment included bilateral pulmonary endarterectomy under deep hypothermic circulatory arrest, followed 11 days later by laparoscopic subtotal colectomy and creation of a primary anastomosis. The patient tolerated both procedures well and recovered normal functional status. Final pathologic analysis of the resected colon mass revealed a pT3N0, stage IIA adenocarcinoma; no adjuvant therapy was administered. At her one-year follow-up visit, the patient was cancer-free, remained on lifelong apixaban anticoagulation, and was undergoing routine monitoring and genetic counseling. This case highlights the need for multidisciplinary management of a patient with severe chronic thromboembolic pulmonary hypertension and a concomitant malignancy.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Hypertension, Pulmonary , Pulmonary Embolism , Adult , Colonic Neoplasms/complications , Colonic Neoplasms/diagnosis , Colonic Neoplasms/surgery , Colorectal Neoplasms, Hereditary Nonpolyposis/complications , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/surgery , Female , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/etiology , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , SyndromeABSTRACT
BACKGROUND: The role of ureteral catheters in left-sided colectomies and proctectomies remains debated. Given the rarity of ureteral injury, prior retrospective studies were underpowered to detect potentially small, but meaningful differences. This study seeks to determine the role and morbidity of ureteral catheters in left-sided colectomy and proctectomy using a large, national database. METHODS: The National Surgical Quality Improvement Project from 2012 to 2018 was queried. Left-sided colectomies or proctectomies were included. Propensity score matching and multivariable logistic regression analysis was performed. RESULTS: 8419 patients with ureteral catherization and 128,021 patients without catheterization were included. After matching, there was not a significant difference in ureteral injury between the groups (0.7% with vs 0.9% without, p = 0.07). Ureteral catheters were associated with increased overall morbidity and longer operative time. Increasing body mass index, operations for diverticular disease, conversion to open, T4 disease and increasing operative complexity were associated with ureteral injury (p < 0.01 for all). CONCLUSIONS: Ureteral catheterization was not associated with decreased rates of ureteral injury when including all left-sided colectomies. High-risk patients for ureteral injury include those with obesity, diverticular disease, and conversion to open. Selective ureteral catheterization may be warranted in these settings.
Subject(s)
Diverticular Diseases , Laparoscopy , Proctectomy , Colectomy/adverse effects , Humans , Laparoscopy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Proctectomy/adverse effects , Retrospective Studies , Urinary CathetersABSTRACT
Bioethanol production from lignocellulosic biomass has received increasing attention over the past decade. Many attempts have been made to reduce the cost of bioethanol production by combining the separate steps of the process into a single-step process known as consolidated bioprocessing. This requires identification of organisms that can efficiently decompose lignocellulose to simple sugars and ferment the pentose and hexose sugars liberated to ethanol. There have been many attempts in engineering laboratory strains by adding new genes or modifying genes to expand the capacity of an industrial microorganism. There has been less attention in improving bioethanol-related processes utilizing natural variation existing in the natural ecotypes. In this study, we sought to identify genomic loci contributing to variation in saccharification of cellulose and fermentation of glucose in the fermenting cellulolytic fungus Neurospora crassa through quantitative trait loci (QTL) analysis. We identified one major QTL contributing to fermentation of glucose and multiple putative QTL's underlying saccharification. Understanding the natural variation of the major QTL gene would provide new insights in developing industrial microbes for bioethanol production.
Subject(s)
Biological Variation, Population/genetics , Ethanol/metabolism , Neurospora crassa/genetics , Quantitative Trait Loci , Fermentation , Industrial Microbiology , Sugars/metabolismABSTRACT
The circadian clock controls daily activities at the cellular and organismic level, allowing an organism to anticipate incoming stresses and to use resources accordingly. The circadian clock has therefore been considered a fitness trait in multiple organisms. However, the mechanism of how circadian clock variation influences organismal reproductive fitness is still not well understood. Here we describe habitat-specific clock variation (HSCV) of asexual reproduction in Neurospora discreta, a species that is adapted to 2 different habitats, under or above tree bark. African (AF) N. discreta strains, whose habitat is above the tree bark in light-dark (LD) conditions, display a higher rhythmicity index compared with North American (NA) strains, whose habitat is under the tree bark in constant dark (DD). Although AF-type strains demonstrated an overall fitness advantage under LD and DD conditions, NA-type strains exhibit a habitat-specific fitness advantage in DD over the LD condition. In addition, we show that allelic variation of the clock-controlled gene, Ubiquinol cytochrome c oxidoreductase (NEUDI_158280), plays a role in HSCV by modulating cellular reactive oxygen species levels. Our results demonstrate a mechanism by which local adaptation involving circadian clock regulation influences reproductive fitness.
Subject(s)
Circadian Clocks/genetics , Circadian Rhythm , Ecosystem , Genetic Fitness , Neurospora/physiology , Reproduction, Asexual/genetics , Adaptation, Physiological , Alleles , CLOCK Proteins/genetics , Circadian Clocks/physiology , Neurospora/genetics , PhotoperiodABSTRACT
BACKGROUND: Colovesical fistula (CVF) is an uncommon complication of diverticulitis. Substantial heterogeneity exists in the perioperative management of this condition. We seek to evaluate the role of bladder leak testing, closed suction drainage, prolonged bladder catheter usage, and routine postoperative cystogram in the management of CVF. STUDY DESIGN: This is a retrospective study from a single academic health center investigation patients undergoing operation for diverticular CVF from 2005 to 2015 (n = 89). RESULTS: Patients undergoing operative repair for diverticular CVF resection had a mortality of 4% and overall morbidity of 46%. Intraoperative bladder leak test was performed in 36 patients (40%) and demonstrated a leak in 4 patients (11%). No patients with a negative intraoperative bladder leak test developed a urinary leak. Overall, five (6%) patients developed postoperative bladder leak. Three were identified by elevated drain creatinine and two by cystogram. The diagnostic yield of routine cystogram was 3%. All bladder leaks were diagnosed between postoperative day 3 and 7. Of patients with a postoperative bladder leak, none required reoperation and all resolved within 2 months. CONCLUSIONS: There is significant variability in the management of patients undergoing operation for CVF. Routine intraoperative bladder leak test should be performed. Cystogram may add cost and is low yield for routine evaluation for bladder leak after operation for CVF. Urinary catheter removal before postoperative day 7 should be considered.
Subject(s)
Disease Management , Diverticulitis, Colonic/complications , Drainage/methods , Intestinal Fistula/therapy , Perioperative Care/methods , Diverticulitis, Colonic/surgery , Female , Humans , Intestinal Fistula/diagnosis , Intestinal Fistula/etiology , Male , Middle Aged , Postoperative Complications , Retrospective Studies , UrographyABSTRACT
BACKGROUND: To evaluate the feasibility of use of rectal mucosal grafts for augmentation urethroplasty. METHODS: A series of five patients who underwent rectal mucosal graft urethroplasty for urethral stricture disease were identified. Descriptive statistics were used to describe these patients. Primary endpoints were recurrence of stricture and perioperative morbidity. RESULTS: Five patients underwent rectal mucosal graft augmentation urethroplasty. Four had a history of prior buccal mucosal graft (BMG) urethroplasty and one had a history of head and neck cancer. Rectal mucosa was noted to be thinner and required more tailoring than buccal mucosa. All patients had patent urethras at time of postoperative retrograde urethrogram. A small diverticulum was noted in one patient with no further sequelae. No complications from rectal mucosal graft harvest were noted. All patients with prior buccal grafting subjectively preferred the rectal graft due to fewer side effects. Subjectively, patients with prior buccal grafts preferred the post-operative recovery following rectal mucosal graft urethroplasty. CONCLUSIONS: Rectal mucosal graft augmentation urethroplasty is a safe alternative in patients with contraindications to buccal grafting with limited morbidity.
ABSTRACT
BACKGROUND: Sigmoid volvulus is an uncommon cause of bowel obstruction that is historically associated with high morbidity and mortality. The objective of this study was to evaluate contemporary management of sigmoid volvulus and the safety of primary anastomosis in patients with sigmoid volvulus. METHODS: The National Surgical Quality Improvement Project from 2012 to 2015 was queried for patients with colonic volvulus who underwent left-sided colonic resection. A propensity score-matched analysis was performed to compare patients with sigmoid volvulus undergoing colectomy with primary anastomosis without proximal diversion to colectomy with end colostomy. RESULTS: Two thousand five hundred thirty-eight patients with sigmoid volvulus were included for analysis. Patients had a median age of 68 years (interquartile range, 55-80) and 79% were fully independent preoperatively. Fifty-one percent of operations were performed emergently. One thousand eight hundred thirteen (71%) patients underwent colectomy with anastomosis, 240 (10%) colectomy with anastomosis and proximal diversion, and 485 (19%) colectomy with end colostomy. Overall, 30-day mortality and morbidity were 5 and 40%, respectively. After propensity score matching, mortality, overall morbidity, and serious morbidity were similar between groups. CONCLUSIONS: Sigmoid volvulus occurs in elderly and debilitated patients with significant morbidity, mortality, and lifestyle implications. In selected patients, anastomosis without proximal diversion in patients with sigmoid volvulus results in similar outcomes to colectomy with end colostomy.
Subject(s)
Colectomy/methods , Colostomy , Intestinal Volvulus/surgery , Sigmoid Diseases/surgery , Aged , Aged, 80 and over , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Anastomotic Leak/etiology , Databases, Factual , Emergencies , Female , Humans , Male , Middle Aged , Operative Time , Propensity Score , Reoperation , Surgical Wound Infection/etiology , Treatment OutcomeABSTRACT
The demand for renewable and sustainable energy has generated considerable interest in the conversion of cellulosic biomass into liquid fuels such as ethanol using a filamentous fungus. While attempts have been made to study cellulose metabolism through the use of knock-out mutants, there have been no systematic effort to characterize natural variation for cellulose metabolism in ecotypes adapted to different habitats. Here, we characterized natural variation in saccharification of cellulose and fermentation in 73 ecotypes and 89 laboratory strains of the model fungus Neurospora crassa. We observed significant variation in both traits among natural and laboratory generated populations, with some elite strains performing better than the reference strain. In the F1 population N345, 15% of the population outperformed both parents with the top performing strain having 10% improvement in ethanol production. These results suggest that natural alleles can be exploited through fungal breeding for developing elite industrial strains for bioethanol production.
Subject(s)
Ethanol/metabolism , Industrial Microbiology , Neurospora crassa/metabolism , Biomass , Cellulose/metabolism , Ecotype , Fermentation , Neurospora crassa/geneticsABSTRACT
BACKGROUND: The impact of process improvement through surgeon feedback on outcomes is unclear. OBJECTIVE: We sought to evaluate the effect of biannual surgeon-specific feedback on outcomes and adherence to departmental and Surgical Care Improvement Project process measures on colorectal surgery outcomes. DESIGN: This was a retrospective analysis of prospectively collected 100% capture surgical quality improvement data. SETTING: This study was conducted at the department of colorectal surgery at a tertiary care teaching hospital from January 2008 through December 2013. MAIN OUTCOME MEASURES: Each surgeon was provided with biannual feedback on process adherence and surgeon-specific outcomes of urinary tract infection, deep vein thrombosis, surgical site infection, anastomotic leak, 30-day readmission, reoperation, and mortality. We recorded adherence to Surgical Care Improvement Project process measures and departmentally implemented measures (ie, anastomotic leak testing) as well as surgeon-specific outcomes. RESULTS: We abstracted 7975 operations. There was no difference in demographics, laparoscopy, or blood loss. Adherence to catheter removal increased from 73% to 100% (p < 0.0001), whereas urinary tract infection decreased 52% (p < 0.01). Adherence to thromboprophylaxis administration remained unchanged as did the deep vein thrombosis rate (p = not significant). Adherence to preoperative antibiotic administration increased from 72% to 100% (p < 0.0001), whereas surgical site infection did not change (7.6%-6.6%; p = 0.3). There were 2589 operative encounters with anastomoses. For right-sided anastomoses, the proportion of handsewn anastomoses declined from 19% to 1.5% (p < 0.001). For left-sided anastomoses, without diversion, anastomotic leak testing adherence increased from 88% to 95% (p < 0.01). Overall leak rate decreased from 5.2% to 2.9% (p < 0.05). LIMITATIONS: Concurrent process changes make isolation of the impact from individual process improvement changes challenging. CONCLUSIONS: Nearly complete adherence to process measures for deep vein thrombosis and surgical site infection did not lead to measureable outcomes improvement. Process measure adherence was associated with decreased rate of anastomotic leak and urinary tract infection. Biannual surgeon-specific feedback of outcomes was associated with improved process measure adherence and improvement in surgical quality.
Subject(s)
Colorectal Surgery/standards , Digestive System Surgical Procedures/methods , Feedback , Guideline Adherence/statistics & numerical data , Postoperative Complications/prevention & control , Quality Improvement , Surgeons , Adult , Aged , Anastomosis, Surgical/methods , Anastomotic Leak/epidemiology , Anastomotic Leak/prevention & control , Antibiotic Prophylaxis , Female , Hospitals, Teaching , Humans , Male , Middle Aged , Mortality , Outcome and Process Assessment, Health Care , Patient Readmission , Postoperative Complications/epidemiology , Practice Guidelines as Topic , Reoperation , Retrospective Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Tertiary Care Centers , Urinary Catheterization , Urinary Tract Infections/epidemiology , Urinary Tract Infections/prevention & control , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & controlABSTRACT
BACKGROUND: Bowel preparation in elderly patients is associated with physiologic derangements that may result in postoperative complications. The aim of this study is to determine the impact of bowel preparation on postoperative outcomes in elderly patients. METHODS: Patients age 75 years and older who underwent elective colectomy were identified from the 2012-2014 American College of National Surgical Quality Improvement Program (ACS-NSQIP database). Patients were grouped into no bowel preparation, mechanical bowel preparation (MBP), oral antibiotic preparation (OABP), or combined MBP + OABP. Logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There were 4829 patients included in the analysis. Morbidity was 34.3% in no bowel prep, 32.4% in MBP, 24.8% in OABP, and 24.6% in MBP + OABP groups (p < 0.001). The MBP + OABP group compared with no bowel prep was associated with reduced rates of anastomotic leak, ileus, superficial surgical site infection (SSI), organ space SSI, respiratory compromise, and reduced length of stay. There was no difference in the rate of acute kidney injury between the groups. CONCLUSION: MBP + OABP was associated with reduced morbidity compared with no bowel preparation in elderly patients undergoing elective colorectal resection. MBP alone was not associated with differences in outcomes compared with no bowel preparation. The use of MBP + OABP is safe and effective in elderly patients undergoing elective colectomy.
Subject(s)
Colectomy/adverse effects , Colonic Diseases/surgery , Elective Surgical Procedures/adverse effects , Postoperative Complications/prevention & control , Preoperative Care , Aged , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Colonic Diseases/complications , Colonic Diseases/pathology , Databases, Factual , Female , Humans , Logistic Models , Male , Postoperative Complications/epidemiology , Quality Improvement , Retrospective StudiesABSTRACT
INTRODUCTION: Robotic colorectal surgery is being increasingly adopted. Our objective was to compare early postoperative outcomes between robotic and laparoscopic colectomy in a nationally representative sample. METHODS: The American College of Surgeons National Surgical Quality Improvement Project Colectomy Targeted Dataset from 2012 to 2014 was used for this study. Adult patients undergoing elective colectomy with an anastomosis were included. Patients were stratified based on location of colorectal resection (low anterior resection (LAR), left-sided resection, or right-sided resection). Bivariate data analysis was performed, and logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There were a total of 25,998 laparoscopic colectomies (30 % LAR's, 45 % left-sided, and 25 % right-sided) and 1484 robotic colectomies (54 % LAR's, 28 % left-sided, and 18 % right-sided). The risk-adjusted overall morbidity, serious morbidity, and mortality were similar between laparoscopic and robotic approaches in all anastomotic groups. Patients undergoing robotic LAR had a lower conversion rate (OR 0.47, 95 % CI 1.20-1.76) and postoperative sepsis rate (OR 0.49, 95 % CI 0.29-0.85) but a higher rate of diverting ostomies (OR 1.45, 95 % CI 1.20-1.76). Robotic right-sided colectomies had significantly lower conversion rates (OR 0.58, 95 % CI 0.34-0.96). Robotic colectomy in all groups was associated with a longer operative time (by 40 min) and a decreased length of stay (by 0.5 days). CONCLUSIONS: In a nationally representative sample comparing laparoscopic and robotic colectomies, the overall morbidity, serious morbidity, and mortality between groups are similar while length of stay was shorter by 0.5 days in the robotic colectomy group. Robotic LAR was associated with lower conversion rates and lower septic complications. However, robotic LAR is also associated with a significantly higher rate of diverting ostomy. The reason for this relationship is unclear. Surgeon factors, patient factors, and technical factors should be considered in future studies.
Subject(s)
Colectomy/methods , Elective Surgical Procedures/methods , Laparoscopy , Quality Improvement , Robotic Surgical Procedures , Adult , Aged , Aged, 80 and over , Colectomy/mortality , Conversion to Open Surgery/statistics & numerical data , Databases, Factual , Elective Surgical Procedures/mortality , Female , Follow-Up Studies , Humans , Laparoscopy/mortality , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Operative Time , Outcome Assessment, Health Care , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/mortalityABSTRACT
With a growing need for sustainable resources research has become highly interested in investigating the structure and physical properties of biomaterials composed of natural macromolecules. In this study, we assessed the structural, morphological, and thermal properties of blended, regenerated films comprised of cellulose, lignin, and hemicellulose (xylan) using the ionic liquid 1-allyl-3-methylimidazolium chloride (AMIMCl). Attenuated total reflectance Fourier transform infrared (ATR-FTIR) analysis, scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray scattering, and thermogravimetric analysis (TGA) were used to qualitatively and quantitatively measure bonding interactions, morphology, and thermal stability of the regenerated films. The results demonstrated that the regenerated films' structural, morphological, and thermal character changed as a function of lignin-xylan concentration. The decomposition temperature rose according to an increase in lignin content and the surface topography of the regenerated films changed from fibrous to spherical patterns. This suggests that lignin-xylan concentration alters the self-assembly of lignin and the cellulose microfibril development. X-ray scattering confirms the extent of the morphological and molecular changes. Our data reveals that the inter- and intra-molecular interactions with the cellulose crystalline domains, along with the amount of disorder in the system, control the microfibril dimensional characteristics, lignin self-assembly, and possibly the overall material's structural and thermal properties.
Subject(s)
Biocompatible Materials/chemistry , Cellulose/chemistry , Ionic Liquids/chemistry , Lignin/chemistry , Polysaccharides/chemistry , Temperature , Tensile Strength , ThermogravimetryABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly fatal malignancy characterized by resistance to chemotherapy. Currently, gemcitabine is the agent used most commonly but demonstrates only a partial response. The transcription factor nuclear factor-kappaB (NF-κB), known to be involved in the inflammatory response, is constitutively activated in PDAC and further activated by gemcitabine. Our aim was to examine the effects of targeted NF-κB suppression on gemcitabine resistance using an in vivo tumor growth model. METHODS: To suppress the NF-κB pathway, the mutant IκBα super-repressor protein was stably expressed in PaCa-2 human PDAC cells. Athymic mice were injected subcutaneously with IκBα-super-repressor (SR) or vector-expressing PaCa-2 cells and randomized to receive phosphate-buffered saline (PBS) or 100 mg/kg gemcitabine(gem) for 4 weeks. RESULTS: The mean increase in tumor volume was 47 mm(3) (89%) and 196 mm(3) (326%) in gem/SR and gem/vector groups, respectively (P = .03). The PBS-treated groups demonstrated greater tumor growth, â¼340 mm(3) (850%) increase, in both PBS/vector and PBS/SR groups. Intratumoral NF-κB activity was decreased in gem/SR compared with the gem/vector group (P = .04). Decreased Ki-67 positivity was noted in gem/SR (49%) versus gem/vector tumors (73%) (P = .04), with no difference in apoptosis (apoptag, P = .3) or angiogenesis (CD31+, P = .9). CONCLUSION: Stable IκBα-SR expression in vivo potentiated the antitumor effects of gemcitabine, resulting in decreased tumor growth in association with decreased cell proliferation. Molecular suppression of the NF-κB pathway decreases successfully gemcitabine resistance in a relatively chemoresistant PDAC line. Thus, NF-κB-targeted agents may complement gemcitabine-based therapies and decrease chemoresistance in patients with PDAC.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm/drug effects , I-kappa B Proteins/pharmacology , Pancreatic Neoplasms/drug therapy , Animals , Antimetabolites, Antineoplastic/pharmacology , Biomarkers, Tumor/antagonists & inhibitors , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Administration Schedule , Humans , I-kappa B Proteins/therapeutic use , Male , Mice , Mice, Nude , NF-KappaB Inhibitor alpha , NF-kappa B/antagonists & inhibitors , Pancreatic Neoplasms/metabolism , Random Allocation , Xenograft Model Antitumor Assays , GemcitabineSubject(s)
Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/pathology , Rectal Diseases/complications , Rectal Diseases/pathology , Rectum/surgery , Adult , Biopsy, Needle , Follow-Up Studies , Histiocytosis, Langerhans-Cell/drug therapy , Humans , Immunohistochemistry , Male , Rare Diseases , Rectal Diseases/surgery , Risk Assessment , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Obesity is an established risk factor for pancreatic adenocarcinoma. No study has examined specifically the influence of obesity on malignant risk in patients with intraductal papillary mucinous neoplasm (IPMN), a group at substantial risk of pancreatic adenocarcinoma. We hypothesize that obesity is associated with a greater frequency of malignancy in IPMN. METHODS: Data on patients undergoing resection for IPMN between 1992 and 2012 at a high-volume university institution were collected prospectively. Clinicopathologic and demographic parameters were reviewed. Patients were classified according to World Health Organization categories of body mass index (BMI). Malignancy was defined as high-grade dysplastic or invasive IPMN. RESULTS: We collected data on 357 patients who underwent resection for IPMN. Of these, 274 had complete data for calculation of preoperative BMI and 31% had malignant IPMN. Of 254 patients with a BMI of <35 kg/m(2), 30% had malignant IPMN versus 50% in patients with BMI of ≥35 (P = .08). In branch-duct IPMN, patients with a BMI of <35 had 12% of malignant IPMN compared with 46% in severely obese patients (P = .01). Alternatively, in main-duct IPMN, no difference was found in the malignancy rate (48% vs 56%; P = .74). CONCLUSION: These findings suggest that obesity is associated with an increased frequency of malignancy in branch-duct IPMN. Obesity is a potentially modifiable risk factor that may influence oncologic risk stratification, patient counseling, and surveillance strategy.
Subject(s)
Adenocarcinoma, Mucinous/etiology , Carcinoma, Pancreatic Ductal/etiology , Carcinoma, Papillary/etiology , Obesity/complications , Pancreatic Neoplasms/etiology , Adenocarcinoma, Mucinous/surgery , Aged , Body Mass Index , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Papillary/surgery , Female , Humans , Male , Neoplasm Recurrence, Local , Pancreatic Neoplasms/surgery , Prospective Studies , Risk , Smoking/adverse effectsABSTRACT
Pancreatic cancer is one of the deadliest cancers, mostly diagnosed at late stages. Patients with pancreatic cysts are at higher risk of developing cancer and their surveillance can help to diagnose the disease in earlier stages. In this retrospective study we collected a corpus of 1064 records from 44 patients at Indiana University Hospital from 1990 to 2012. A Natural Language Processing (NLP) system was developed and used to identify patients with pancreatic cysts. NegEx algorithm was used initially to identify the negation status of concepts that resulted in precision and recall of 98.9% and 89% respectively. Stanford Dependency parser (SDP) was then used to improve the NegEx performance resulting in precision of 98.9% and recall of 95.7%. Features related to pancreatic cysts were also extracted from patient medical records using regex and NegEx algorithm with 98.5% precision and 97.43% recall. SDP improved the NegEx algorithm by increasing the recall to 98.12%.
Subject(s)
Electronic Health Records , Health Records, Personal , Natural Language Processing , Pancreatic Cyst/classification , Pancreatic Cyst/diagnosis , Vocabulary, Controlled , Algorithms , Artificial Intelligence , Data Mining/methods , Decision Support Systems, Clinical , Humans , Pattern Recognition, Automated/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
INTRODUCTION: Gemcitabine is standard treatment for pancreatic cancer but has limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF-κB) can promote chemoresistance and is therefore an attractive therapeutic target. We hypothesize that NF-κB suppression with the novel, orally bioavailable inhibitor dimethylamino parthenolide (DMAPT) will sensitize pancreatic cancer cells to gemcitabine. METHODS: BxPC-3, PANC-1, and MIA PaCa-2 human pancreatic cancer cell lines were treated with gemcitabine and/or DMAPT. Effects on the NF-κB pathway were determined by electrophoretic mobility shift assay, ELISA, or Western blot. Proliferation and apoptosis were measured by cell counts and ELISA, respectively. The effect of gemcitabine in vivo was determined using a MIA PaCa-2 heterotopic xenograft model. RESULTS: Gemcitabine induced NF-κB activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased the level of the NF-κB inhibitor IκBα in BxPC-3 and PANC-1 cells. DMAPT prevented the gemcitabine-induced activation of NF-κB. The combination of DMAPT/gemcitabine inhibited pancreatic cancer cell growth more than either agent alone. Gemcitabine also induced intratumoral NF-κB activity in vivo. CONCLUSIONS: DMAPT enhanced the anti-proliferative effects of gemcitabine in association with NF-κB suppression in pancreatic cancer cells in vitro. Furthermore, gemcitabine induced NF-κB activity in vivo, thus supporting the evaluation of NF-κB-targeted agents to complement gemcitabine-based therapies.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm/drug effects , NF-kappa B/antagonists & inhibitors , Pancreatic Neoplasms/drug therapy , Sesquiterpenes/pharmacology , Animals , Antimetabolites, Antineoplastic/therapeutic use , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Resistance, Neoplasm/physiology , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Humans , Mice , Mice, Nude , NF-kappa B/metabolism , Pancreatic Neoplasms/pathology , GemcitabineABSTRACT
BACKGROUND: Single-port laparoscopy remains a novel technique in the field of colorectal surgery. Several small series have examined its safety for colon resection. OBJECTIVE: Our aim was to analyze our entire experience and short-term outcomes with single-port laparoscopic right hemicolectomy since its introduction at our institution. We assert that this approach is feasible and safe for the wide array of patients and indications encountered by a colorectal surgeon. DESIGN: This is a retrospective analysis of prospectively gathered data for all patients who underwent single-port laparoscopic right hemicolectomy with the use of standard laparoscopic instrumentation, for malignant or benign disease, between July 2009 and November 2010 in a high-volume, academic, colorectal surgery practice. MAIN OUTCOME MEASURES: Demographic, clinical, operative, and pathologic factors were reviewed and analyzed. All conversions to conventional laparoscopic or open operations were considered in this analysis. RESULTS: One hundred patients underwent single-port laparoscopic right hemicolectomy during the study period. Mean age was 63 years, and 61% of the patients were men. Forty-three percent had undergone previous abdominal surgery, and the median body mass index was 26 (range, 18-46). Median ASA classification was 3 (range, 1-4). Five percent of the operations were performed urgently, and 56% were performed for carcinoma, of which half were T3 or T4 tumor stage. Median operative duration was 105 (range, 64-270) minutes. Mean and median blood loss was 106 and 50 mL. Two percent required conversion to multiport laparoscopy, and 4% converted to the open approach. Median postoperative stay was 4 (range, 2-48) days. Median lymph node number was 18 (range, 11-42). There was one mortality in this series. Morbidity, including wound infection, was 13%. CONCLUSIONS: This represents the largest experience with single-port laparoscopic right hemicolectomy to date. This technique was used with acceptable morbidity and mortality and without compromise of conventional oncologic parameters by colorectal surgeons experienced in minimally invasive technique. These findings support the use of a single-port approach for patients requiring right hemicolectomy.
Subject(s)
Colectomy/methods , Colonic Neoplasms/surgery , Laparoscopy/methods , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Inflammatory Bowel Diseases/surgery , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Limited data are available regarding the natural history of patients undergoing primary surveillance for intraductal papillary mucinous neoplasm (IPMN). We hypothesize that symptoms, radiologic characteristics, and cytopathology will predict cancer risk during surveillance. METHODS: Between March 2002 and March 2010, 522 patients were diagnosed with IPMN at a single, high-volume institution. Low versus high oncologic risk was stratified prospectively. Patients with under 3 months of surveillance were excluded. RESULTS: Two hundred ninety-two patients underwent primary surveillance for IPMN. Two hundred forty-four (84%) were classified as low-risk IPMN. Mean surveillance duration was 35 (4-99) months. Thirty (12%) patients initially stratified as low-risk developed a new indication for pancreatic resection. Only 28 underwent resection, and pathologic tissue analysis revealed 27 (96%) low-grade IPMN and one (4%) high-grade dysplastic IPMN. Overall, two (1%) patients initially determined to be low-risk developed invasive cancer. Forty-eight (16%) patients stratified as high-risk IPMN were initially managed nonoperatively. Of the 13 (27%) high-risk patients that died during follow-up, two (15%) died from pancreatic cancer. CONCLUSIONS: Progression to pancreatic cancer during surveillance for low-risk IPMN was rare. Current indications for resection did not forecast malignancy. Poor operative candidates with high-risk IPMN progressed to invasive cancer more commonly, though a substantial portion succumbed to non-IPMN-related death.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Cohort Studies , Disease Progression , Early Detection of Cancer , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Pancreas/surgery , Pancreatectomy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Population Surveillance , Prognosis , Retrospective Studies , RiskABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a propensity for early metastasis that is often encountered unexpectedly at operation. Our objective was to examine the effect of the time interval between preoperative imaging and attempted resection and the venue in which imaging was performed on the frequency of unanticipated metastasis (UM) encountered at operation. We hypothesize that imaging obtained locally at our hospital and within 4 weeks of operation will result in a lesser frequency of UM encountered at operation. METHODS: Between January 2004 and December 2009, records of patients undergoing planned pancreatic resection for PDAC at a high volume pancreatic surgery center were compiled. Exclusion criteria included neoadjuvant therapy, prior pancreatic resection, or evidence of metastasis on imaging. Review and analysis of clinical, radiographic, operative, and pathologic data were undertaken. Frequency of UM and outcome of resection was compared with the interval between most recent cross-sectional imaging (dual-phase contrast-enhanced CT or MRI) and operation defined as imaging-to-operation interval (IOI). RESULTS: Four-hundred eighty-seven patients met eligibility requirements for the study: 431 (88%) proximal and 56 (12%) distal PDAC. 202 (41%) patients had their most recent imaging performed at an outside institution, and no difference in the rates of UM was observed whether imaging was conducted at our institution or at an outside institution (P > .05). Of 329 with complete imaging information for analysis, UM were discovered in 60 (18%): 52 (18%) of 293 proximal PDAC and 8 (22%) of 36 distal PDAC. In proximal PDAC, there was a linear relationship in the frequency of UM as a function of the weekly IOI (R(2) = .99; P = .006). For distal PDAC, no significant difference in the frequency of UM as a function of IOI was observed. CONCLUSION: For proximally located PDAC, the frequency of UM increases with greater imaging-to-operation interval. Performing imaging at a high volume, pancreatic surgery center compared with elsewhere was not associated with a decrease in the rate of UM. Obtaining timely diagnostic imaging for proximal PDAC may improve the accuracy of preoperative staging, and thereby reduce the number of operations not producing oncologic benefit.