Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database.

BACKGROUND: A subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. METHODS: Patients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). RESULTS: A total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04-1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69-0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). CONCLUSION: AC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

A retrospective comparison of 90-day outcomes, length of stay, and readmissions between robotic-assisted and laparoscopic colectomy.

Investigations generally assess 30 days of perioperative outcomes with robotic-assisted and laparoscopic colectomy. Outcomes beyond 30 days serve as a quality metric of surgical services and an assessment of 90 days of outcomes may have greater clinical utility. The purpose of this study was to assess 90 days of outcomes, length of stay (LOS), and readmissions among patients who underwent a robotic-assisted versus laparoscopic colectomy using a national database. Patients undergoing either robotic-assisted or laparoscopic colectomy were identified using Current Procedural Terminology (CPT) codes within PearlDiver, a national, inpatient records database from 2010 to 2019. Outcomes were defined using the National Surgical Quality Improvement Program (NSQIP) risk calculator and identified using International Classification of Disease (ICD) diagnosis codes. Categorical variables were compared using chi-square tests, and continuous variables were compared using paired t tests. Covariate-adjusted regression models were also constructed to evaluate these associations while accounting for potential confounders. A total of 82,495 patients were assessed in this study. At 90 days, patients of the laparoscopic colectomy cohort experienced a higher rate of complications than patients who underwent robotic-assisted colectomy (9.5 vs. 6.6%, p < 0.001). There were no significant differences in LOS (6 vs. 6.5 days, p = 0.08) and readmissions (6.1 vs. 6.7%, p = 0.851) at 90 days. Patients undergoing robotic-assisted colectomy have a lower risk for morbidity at 90 days. Neither approach is superior for LOS nor 90 days of readmissions. Both techniques are effective minimally invasive procedures, yet patients may gain a greater risk benefit from robotic colectomy.

Evaluation of a commonly used tool: Does the 5-item frailty index predict phenotypic frailty?

BACKGROUND: The simplified frailty index (sFI) is a commonly used instrument to estimate postoperative risk, but its correlation with phenotypic frailty has been questioned. This study evaluates the relationship between sFI and phenotypic frailty, as measured by the Sinai Abbreviated Geriatric Evaluation (SAGE). METHODS: Charts were retrospectively reviewed from patients ≥75 years old who underwent surgery between 2012-2022. The sFI score was calculated by adding 1 point for hypertension, COPD, congestive heart failure, functional dependence, and diabetes (score 0-5). SAGE was calculated by adding 1 point for normal gait speed, normal Mini-Cog©, and independent activities of daily living (ADL) (0-3). Spearman rank correlation was used to test the relationship between sFI and SAGE. SAGE components were used as binary-dependent outcomes in covariate-adjusted logistic regression modeling to evaluate associations with sFI scores while adjusting for potential confounders. RESULTS: 334 patients were assessed, with a mean age of 84.0. SAGE and sFI scores were significantly associated, with a modest inverse relationship (r=-0.24, p<0.0001). Each 1-point increase in sFI score was associated with increased odds of ADL deficit (OR 2.3, 95%CI [1.5-3.8], p<0.0001) and abnormal gait speed (OR 1.9, 95%CI 1.2-3.0, p<0.01). The sFI score was not associated with deficits in the Mini-Cog (OR 1.5, 95%CI [0.96-2.3], p=0.07). CONCLUSION: Higher sFI was significantly associated with increased phenotypic frailty, particularly with the loss of physical condition and function but not associated with cognitive deficit. Therefore, sFI may not be an appropriate tool to estimate postoperative complications related to cognition, such as delirium risk.

Accuracy of National Surgical Quality Improvement Program Risk Calculator Among Elderly Patients Undergoing Pancreas Resection.

INTRODUCTION: A preoperative goals-of-care discussion is essential in maintaining the autonomy of older adults who require surgery. The purpose of this study was to determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator and its association with age for patients who underwent pancreatectomy. METHODS: Using the American College of Surgeons NSQIP database, patients who underwent pancreatectomy between 2012 and 2015 were identified. Age was categorized into three groups: 18-64, 65-79, and 80-89 y. Analysis of variance and Pearson correlation coefficients were employed to assess differences between age categories in predicted and actual mortality and morbidity. Covariate-adjusted logistic regression models were employed to evaluate associations while accounting for potential confounders. RESULTS: A total of 17,906 patients were included. The correlation between actual and predicted mortality was low (r = 0.14, P < 0.001). This correlation was weakest for the age category 80-89 y (r = 0.04, P = 0.07) and strongest for 65-79 y category (r = 0.14, P > 0.001). The correlation was weakest among patients who underwent pancreatoduodenectomy (r = 0.06, P = 0.08) and in this group mortality was overestimated for older adults in the age group 80-89 (actual mortality: 3.2% versus predicted mortality: 5.6%, P = 0.08). After adjusting for covariates, the interaction term between age and predicted mortality (P = 0.0021) indicated that the relationship between predicted and actual mortality is significantly influenced by patient age. CONCLUSIONS: The NSQIP risk calculator appears to overestimate mortality and morbidity risk for elderly patients undergoing pancreatoduodenectomy. These predictions should be used with caution in preoperative goals-of-care discussions with patients aged 80 y and older.

Telehealth Adaptation for Multidisciplinary Colorectal Cancer Clinic During the COVID-19 Pandemic.

Background The study objectives were to transition in-person colorectal cancer multidisciplinary clinic (MDC) to a telehealth MDC (tele-MDC) format and to assess early outcomes.  Methods A colorectal tele-MDC was devised, in which patients used remote-access technology while supervised by a clinician. The team consisted of surgeons, medical oncologists, radiation oncologists, radiologists, and pathologists. Outcomes were assessed with patient and provider surveys, using a 5-point Likert scale (higher = more favorable). Results A total of 18 patients participated in the tele-MDC. Surveyed patients (n=18) and physicians (n=19) were satisfied with the quality of care (mean Likert = 4.93, 4.53, respectively), and low standard deviations (range 0-1.03) across all questions reflected homogeneity in satisfaction with the metrics surveyed. Conclusions This pilot study demonstrates that a functional colorectal cancer tele-MDC is a feasible alternative to in-person MDC during the coronavirus disease 2019 (COVID-19) pandemic, with the potential for a high degree of patient and physician satisfaction.

Metformin use and the risk of anal intraepithelial neoplasia in type II diabetic patients.

AIM: Emerging evidence has suggested that metformin may be protective against the development of human-papillomavirus-related cancers. Anal intraepithelial neoplasia (AIN) is highly associated with human papillomavirus infection and a precancerous status of anal cancer. The aim of this study was to investigate the relationship between metformin usage and the development of AIN in a large national sample. METHODOLOGY: The IBM MarketScan dataset was used to design a nested case-control study from 2010 to 2017. Patients aged 18-65 years with type 2 diabetes mellitus (DM) were evaluated, and cases of AIN were identified. Four controls were randomly selected in the risk set of each case by using incidence density sampling. The association between metformin usage and AIN was assessed using multivariate logistic regression modelling. RESULTS: A total of 258 patients with type 2 DM were diagnosed with AIN during the study interval, and these were matched to 1032 control patients without a diagnosis of AIN. Patients who developed AIN had 38% lower odds of prior metformin use compared to those without a history of AIN (P < 0.01) and this finding remained robust after adjusting for age, sex, human immunodeficiency virus infection and DM complications (P = 0.02). Patients with AIN had 56% lower odds of long-term metformin use compared to control patients (P = 0.01). CONCLUSIONS: An AIN diagnosis in patients with DM is associated with 56% lower likelihood of prior metformin use. This relationship suggests that metformin could potentially play a protective role against AIN. Prospective studies in non-diabetic patients are warranted to examine these findings further.

Predictors of underlying carcinoma in patients with suspected acute diverticulitis.

BACKGROUND: A subset of patients who undergo colon resection for suspected diverticulitis will unexpectedly be found to have cancer. We hypothesized that a subset of variables could be used to help predict a diagnosis of cancer preoperatively. METHODS: National Surgical Quality Improvement Program data (2012-2018) were used to identify all patients with a preoperative diagnosis of diverticulitis who had unexpected cancer using postoperative staging data. Key characteristics of the study groups were compared with χ2 tests and multivariate logistic regression modeling. RESULTS: A total of 17,368 patients were identified with an operative indication of acute diverticulitis. Of these, 164 (0.94%) had an unexpected postoperative diagnosis of cancer. Most cancer patients had locally advanced tumors (T1-2: 15%; T3: 39%; T4: 45%), and 37.1% had positive lymph nodes. Rates of margin positivity and inadequate lymph node harvest were 1.2% and 15.9%, respectively. In bivariate analyses, cancer patients had increased age (P < .01), decreased albumin (P < .001), and increased rates of preoperative anemia (P = .01), sepsis (P < .01), and weight loss (>10% in 6 months) (P < .001). The only variables significantly associated with cancer in multivariate regression analysis were sepsis (odds ratio 2.14, 95% confidence interval [1.3-3.6]; P < .01), weight loss (odds ratio 2.31, 95% confidence interval [1.1-4.4]; P = .01), and preoperative albumin level (odds ratio 0.64, 95% confidence [0.45-0.92]; P < .01). CONCLUSION: An unexpected postoperative diagnosis of cancer occurs in a small percentage of patients with suspected diverticulitis. Surgeons should have a high index of suspicion for cancer in patients with sepsis or malnutrition.

Pathologic complete response is associated with decreased morbidity following rectal cancer resection.

BACKGROUND: There are conflicting data regarding the relationship between pathologic complete response (pCR) and post-operative complications following rectal cancer resection. The objective of this study was to compare the rates of morbidity among pCR patients and non-pCR patients and to identify factors that predict pCR morbidity in a large national database. METHODS: This is a retrospective study using American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted proctectomy data (2016-18). Patients with neoadjuvant chemoradiation therapy followed by proctectomy were included, and divided into pCR and non-pCR groups according to final stage. The groups were compared with Student's t-test, Chi-squared or Fisher's exact test. Multivariate logistic regression models were constructed to estimate the association between pCR status and post-operative morbidity while adjusting for key covariates. RESULTS: 244 pCR and 1656 non-pCR patients were included. pCR patients had higher body mass index (28.1 ± 6.2 vs. 29.1 ± 5.9 kg/m2; p = 0.01) and lower pre-operative stage (T stage, p = 0.03; N stage, p < 0.001). The groups were equivalent with respect to surgical approach, type of surgery, and operative time (p > 0.05). Post-operative complications in pCR patients were less frequent than in non-pCR patients (23.0% vs. 29.3%; p = 0.04). This association was robust to adjustment for confounders in logistic regression, as patients with pCR had decreased odds of post-operative morbidity (OR 0.66, CI [0.43, 0.96], p = 0.04). CONCLUSION: pCR is associated with fewer post-operative complications compared to non-pCR, suggesting that pCR is not a marker of severe pelvic fibrosis. This difference may be due to underlying tumor biology, and associated increased technical challenges resecting larger, non-responsive tumors.

Overall survival and tumor recurrence after surgical resection for primary malignant chest wall tumors: a single-center, single-surgeon experience.

BACKGROUND AND OBJECTIVES: Malignant primary chest wall tumors (PCWTs) comprise a rare group of thoracic tumors with unique anatomical considerations, and experience with wide surgical resection is limited to specialty referral centers and specific diagnoses. We investigated the tumor recurrence and overall survival (OS) for patients with a variety of PCWTs diagnoses at our institution. METHODS: From 1991 to 2010, patients with malignant PCWT undergoing wide surgical resection for curative intent under a single surgeon were reviewed. Diagnosis and grade (if applicable) of surgical pathology, along with patient demographics, neoadjuvant chemotherapy or radiation therapy, and outcomes (complications, recurrence, and OS) at follow-up were analyzed. RESULTS: One hundred fifteen patients were included in the study. The most common tumor diagnoses included pleomorphic sarcoma and liposarcoma. Negative margins were achieved in 70 (74%) of cases. Postoperative complications were reported in 21 (20%) cases. The 5-year survival rate was 54%, while the 10-year survival rate was 29%. The local and distant recurrence rates were 50% and 38%, respectively. OS was significantly less in patients with any recurrence ( p < 0.001) but not significantly different between pathology grades ( p = 0.28). CONCLUSIONS: Wide resection for malignant PCWT is feasible when undertaken for a heterogenous group of diagnoses.

A significant proportion of venous thromboembolism events in general surgical patients occurs after discharge: analysis of the ACS-NSQIP Essentials database.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in general surgical patients. METHODS: The ACS-NSQIP database was queried and VTE data were collected and analyzed to assess the incidence of VTE at a 500-bed, non-profit, teaching, inner city, community hospital and similar peer institutions from January 1, 2006 to December 31, 2011. RESULTS: Post-discharge VTE events accounted for 40% of all VTE events within 30 days of discharge. Data show a significant proportion of post-discharge VTE events that may be preventable with extending VTE prophylaxis in the post-discharge period. CONCLUSION: This is the first paper to report on this high post-discharge incidence of VTE in general surgical patients and to recommend continuation of VTE prophylaxis in the post-discharge period.

EUS-guided colo-enterostomy as a salvage drainage procedure in a high surgical risk patient with small bowel obstruction due to severe ileocolonic anastomotic stricture: a new application of lumen-apposing metal stent (LAMS).

We submit the first case report of a successful EUS-guided transmural LAMS placement to drain the small bowel directly into the transverse colon in a high surgical risk patient with obstruction due to severe anastomotic stricture. We describe our technique for endoscopic colo-enterostomy and are hopeful that this will become a viable option to manage non-operable high-grade distal small bowel obstruction.

Mammary-type myofibroblastoma of the psoas.

Mammary myofibroblastoma is a rare, benign, mesenchymal neoplasm that was first described in the breast in 1987. However, extra-mammary-type myofibroblastoma (MTMF) was not described until 2001 as a distinct entity. We report a case of extra-MTMF arising from the retroperitoneum, which was encountered in our clinic. We also completed a review of the literature using PubMed in patients with extra-MTMF.

Oncologic Risk Stratification Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendiceal Carcinomatosis.

INTRODUCTION: Patients with peritoneal carcinomatosis (PC) of appendiceal origin demonstrate variable oncologic outcomes, despite aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We sought to devise a prognostic risk stratification system for oncologic outcomes following CRS-HIPEC. METHODS: A total of 197 patients undergoing CRS-HIPEC for the treatment of appendiceal PC were reviewed from a prospective database. Kaplan-Meier survival curves and multivariate Cox regression models were used to identify prognostic factors affecting oncologic outcomes. Clinicopathologic variables affecting overall survival (OS) were utilized to develop a prognostic staging system and nomograms. RESULTS: Univariate and multivariate Cox regression analysis indicated that high-grade tumor histology, lymph node metastasis, and incomplete cytoreduction were high-risk features, adversely affecting OS. Patients were stratified on the presence of high-risk features as follows: low-risk patients had no risk factors (n = 102); intermediate-risk patients had one risk factor (n = 49); and high-risk patients had more than one risk factor (n = 46). Median OS for low-risk patients was not reached, and was 43 and 22 months for intermediate-risk and high-risk patients, respectively. Five-year OS was 72, 43, and 13 % for low-, intermediate- and high-risk patients, respectively (p < 0.0003 for low vs. intermediate risk, and p = 0.06 for intermediate vs. high risk). CONCLUSIONS: We propose a three-tier staging system for appendiceal PC following CRS-HIPEC, based on histologic grade, lymph node involvement, and completeness of cytoreduction. The presence of any one or more of these high-risk features significantly decreased survival in our single-institution database and provided the basis for a prognostic staging system and corresponding nomograms.

Aggressive locoregional surgical therapy for gastric peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis from gastric cancer (GPC) responds poorly to systemic chemotherapy. Limited published data demonstrate improved outcomes after aggressive locoregional therapies. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in GPC. METHODS: We prospectively analyzed 23 patients with GPC undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS: CRS/HIPEC was performed for synchronous GPC in 20 patients and metachronous GPC in 3 patients. Adequate CRS was achieved in 22 patients (CC-0 = 17; CC-1 = 5) and median peritoneal cancer index was 10.5. Most patients received preoperative chemotherapy (83 %) and total gastrectomy (78 %). Pathology revealed diffuse histology (65 %), signet cells (65 %) and LN involvement (64 %). Major postoperative morbidity occurred in 12 patients, with 1 in-hospital mortality at postoperative day 66. With median follow-up of 52 months, median overall survival (OS) was 9.5 months (95 % confidence interval 4.7-17.3), with 1- and 3- year OS rates of 50 and 18 %. Median progression-free survival (PFS) was 6.8 months (95 % confidence interval 3.9-14.6). In a multivariate Cox regression model, male gender [hazard ratio (HR) 6.3], LN involvement (HR 1.2), residual tumor nodules (HR 2.4), and >2 anastomoses (HR 2.8) were joint significant predictors of poor OS (χ (2) = 18.2, p = 0.001), while signet cells (HR 8.9), anastomoses >2 (HR 5.5), and male gender (HR 2.4) were joint significant predictors of poor progression (χ (2) = 16.3, p = 0.001). CONCLUSIONS: Aggressive CRS/HIPEC for GPC may confer a survival benefit in select patients with limited lymph node involvement and completely resectable disease requiring less extensive visceral resections.

Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome analysis.

BACKGROUND: Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. METHODS: We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). CONCLUSIONS: Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.

Extensive cytoreductive surgery for appendiceal carcinomatosis: morbidity, mortality, and survival.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis. METHODS: We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan-Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes. RESULTS: Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS. CONCLUSIONS: Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.

Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms.

BACKGROUND: Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons. METHODS: We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan­Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes. RESULTS: Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0­21), 483.5 min (range, 46­1,402), and 800 ml (range, 0­14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox-regression model, tumor grade, age, preoperative SPCI and chemo-naïve status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression. CONCLUSIONS: Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity.

Chronic anti-inflammatory drug therapy inhibits gel-forming mucin production in a murine xenograft model of human pseudomyxoma peritonei.

BACKGROUND: Intraperitoneal accumulation of mucinous ascites in pseudomyxoma peritonei (PMP) promotes an inflammatory/fibrotic reaction that progresses to bowel obstruction and eventual patient demise. Cytokines and inflammation-associated transcription factor binding sites, such as glucocorticoid response elements and COX-2, regulate secretory mucin, specifically MUC2, production. We hypothesized that anti-inflammatory drugs targeting inflammation-associated pathways may reduce mucin production and subsequent disease morbidity in PMP. METHODS: The effects of dexamethasone and Celebrex were assessed in mucin-secreting human colon cancer LS174T cells in vitro and murine xenograft models of LS174T and human appendiceal PMP in vivo by serial parametric measurements, MUC2 transcripts via real-time RT-PCR, and MUC2 protein expression via immunofluorescence assays. RESULTS: Dexamethasone significantly inhibited basal MUC2 mRNA levels in LS174T cells, inhibited mucinous tumor accumulation in an intraperitoneal PMP xenograft model, and prolonged survival in a subcutaneous LS174T xenograft model. Celebrex significantly inhibited sodium butyrate-stimulated MUC2 mRNA levels in LS174T cells and demonstrated a statistically nonsignificant trend toward reduced mucinous tumor growth and prolonged survival in the xenograft models. MUC2 protein analysis by immunofluorescence demonstrated a dual effect of dexamethasone on mucin production and tumor cell count. CONCLUSIONS: Inflammatory mediators are known to regulate mucin production and may promote overexpression of MUC2 by neoplastic cells with goblet cell phenotype in PMP. Anti-inflammatory drugs, dexamethasone and Celebrex, could inhibit extracellular mucin production in PMP by targeting inflammatory cascades and, therefore, may decrease compressive symptoms, increase the disease-free interval, and reduce the extent or frequency of morbid cytoreductive surgeries.