Outcomes of Simultaneous Versus Staged Resection for Stage IV Colorectal Cancer with Synchronous Liver Metastases.

INTRODUCTION: Management of stage IV colorectal cancer with synchronous liver metastases remains debated, as colorectal and liver resections can be performed simultaneously or staged apart. OBJECTIVE: This study aims to determine any demographic or outcome differences between simultaneous and staged resection. PARTICIPANTS: Retrospective review was performed on patients diagnosed with synchronous colorectal primary and liver metastases within Southern California Kaiser Permanente (KP) hospitals between 2010 and 2020. Patients with other metastases on diagnosis or those who did not receive both primary and liver resections were excluded. Demographic and outcome data were collected and analyzed. RESULTS: Of the 113 patients who met criteria, 72 (63.7%) received simultaneous and 41 (36.3%) received staged resection. Demographic data were comparable between simultaneous and staged resection, respectively, including median age of diagnosis, sex, and race. Both groups had similar median length of stay, percentage of major colorectal resection, and percentage of major liver resection. Both groups also had similar rates of radiation therapy, chemotherapy, and immunotherapy. There were no statistically significant difference in complications rates, median follow-up time, median overall survival, and median disease-free survival. CONCLUSIONS: Practice patterns within Southern California KP hospitals favor minor colorectal and liver resections. However, there were no significant differences in demographics, treatment rates, or outcomes between simultaneous and staged resection. While not statistically significant, our findings of a 11.9% higher major liver resection rate and 7.5-month longer median disease-free survival in the staged resection group may benefit from further study with higher power datasets.

Predictors of Progression of Appendiceal Mucinous Neoplasm to Pseudomyxoma Peritonei.

Appendiceal mucinous neoplasm (AMN) can present with a spectrum of disease. Predicting factors in development of pseudomyxoma peritonei (PMP) from AMN could aid in management and treatment. The aim of this study was to determine factors predictive of PMP from AMN. This was a retrospective multicenter study of all patients diagnosed with AMN from 2006-2017. Diagnosis of PMP was compared by (1) patient demographics, (2) tumor characteristics, and (3) surgery. Secondary end points were disease-specific survival (DSS) and overall survival (OS).One-hundred thirty-eight patients with AMN were identified. Thirty-six patients (26.1%) had a ruptured appendix at presentation, and 12 patients (8.7%) were diagnosed with PMP during the study period. Eight patients presented with PMP at the time of surgery. No demographic factors were predictive of PMP. Operative approach and extent of initial resection did not correlate with PMP. Tumor rupture at presentation was the only factor associated with PMP, though only 14% of patients who presented with simple rupture eventually progressed to PMP.OS was not different between those who were diagnosed with PMP and those who were not. DSS was significantly lower for the group diagnosed with PMP (P = .007). Tumor rupture at presentation did not influence OS or DSS. The only factor found to be significantly associated with PMP was tumor rupture at presentation. Diagnosis of PMP did not affect OS but did lead to decreased DSS.In conclusion, though a majority of patients who presented with rupture did not go on to develop PMP, tumor rupture at presentation was the only factor significantly associated with PMP. Diagnosis of PMP did not affect OS at 5 years. In patients with AMN who present with a ruptured appendix on final pathology, we recommended continued surveillance, though overall risk of PMP is relatively low.

Surgical management of appendiceal mucinous neoplasm: Is appendectomy sufficient?

BACKGROUND AND OBJECTIVES: Due to the rarity of appendiceal mucinous neoplasms (AMNs), there are few established treatment guidelines. The clinical course varies from incidental detection to progressive spread with pseudomyxoma peritonei (PMP). This study investigated the extent of resection on the prognosis and outcomes of AMNs. METHODS: This multicenter retrospective study evaluated patients with AMN who underwent surgery between 4/2006 to 9/2017. Primary endpoints included overall survival (OS) and disease-specific survival (DSS). Secondary endpoints included PMP incidence and treatment with cytoreductive surgery (CRS). RESULTS: Of the 138 patients with AMN, 70 patients (54%) underwent appendectomy, 26 (19%) cecectomy, and 37 (27%) right hemicolectomy. The median age was 59.7 years and 57 patients (41%) were male. Males were less likely to undergo cecectomy (P = .03). Rupture rates, tumor characteristics, and incidence of PMP were similar across surgery groups. Median follow-up was 61.3 months. Five-year OS and DSS for the total cohort were 94.9% and 98.6%, respectively, and remained similar across all surgery groups. CRS patients were more likely to undergo right hemicolectomy with no difference in survival by surgery type (P = .03). CONCLUSIONS: Patients with AMN have a good overall prognosis and there may be minimal benefit to performing extended surgical resection in these patients.

Attributable cost of obesity in breast surgery: a matched cohort analysis.

BACKGROUND: The purpose of this study was to determine the economic impact of obesity on patients undergoing mastectomy and breast conservation (BC) for breast cancer. METHODS: An analysis of female patients greater than or equal to 18 years undergoing mastectomy and BC for breast cancer between 2004 and 2010 using the Nationwide Inpatient Sample was conducted. RESULTS: Of 55,903 patients in our study (49,985 mastectomy, 5,918 BC), 3,308 patients (5.92%) were obese. After propensity score matching, the cost for obese patients was higher at $1,826 (P < .0001) for mastectomy and $1,702 for BC (P < .0001). These costs were not significantly associated with overall complications and length of stay for mastectomy in the matched comparison group and not associated with overall complications and minimally associated with longer length of stay in the BC group. CONCLUSION: By controlling for other patient factors, this study shows that obesity is attributable to a significantly higher cost for both BC (29%) and mastectomy (23%).

Race influences stage-specific survival in gastric cancer.

Gastric adenocarcinoma studies show improved survival for Asians but have not reported stage-specific overall survival (OS) or disease-specific survival (DSS) by race. The Surveillance, Epidemiology and End Results database was queried for cases of gastric adenocarcinoma between 1998 and 2008. We evaluated OS and DSS by race and stage. Number of assessed lymph nodes was compared among surgical patients. Of 49,058 patients with complete staging data, 35,300 were white, 7709 were Asian, and 6049 were black. Asians had significantly better OS for all stages (P < 0.001) and significantly better DSS for Stages I (P < 0.0001) and II (P = 0.0006). As compared with blacks, whites had significantly better DSS for Stages I (P < 0.0001), II (P = 0.0055), III (P = 0.0165), and IV (P < 0.0001). Among the 28,133 (57%) surgical patients, average number of evaluated lymph nodes was highest for Asians (P < 0.0001). Among surgical patients with 15 or more nodes evaluated, DSS was worse in blacks with Stage I disease (P < 0.05). Blacks with gastric adenocarcinoma have a worse DSS, which disappears when surgical treatment includes adequate lymphadenectomy. Race-associated survival differences for gastric adenocarcinoma might simply reflect variations in surgical staging techniques and socioeconomic factors.

Deviation from the Standard of Care for Early Breast Cancer in the Elderly: What are the Consequences?

BACKGROUND: For elderly patients with early-stage breast cancer, the standards of care often are not strictly followed due to either clinician biases or patient preferences. The authors hypothesized that forgoing radiation and lymph node (LN) staging for elderly patients with early-stage breast cancer would have a negative impact on survival. METHODS: From the Surveillance, Epidemiology, and End Results Program database, 53,619 women older than 55 years with stage 1 breast cancer who underwent breast conservation surgery were identified. Analyses were performed to compare the characteristics and outcomes of patients who received the standards of care with LN sampling and radiation and those of patients who did not, with control used for confounders. To account for selection bias from covariate imbalance, propensity score matching was performed. Survival was analyzed using the Kaplan-Meier method. RESULTS: Older patients were less likely to receive radiation and LN sampling. These standards of care were associated with improved overall survival rates of 15.8 and 27.1 % after 10 years, respectively (p ≤ 0.0001). This survival advantage persisted after propensity score matching, with a 7.4 % higher survival rate for patients who received radiation and a 16.8 % higher survival rate for those who underwent LN staging (p < 0.0001). Lymph node sampling and radiation therapy also conferred a statistically significant improvement in breast cancer-specific survival, with 1.3 and 2.6 % lower mortality rates respectively in the radiated and LN biopsy groups (p < 0.0001). CONCLUSIONS: As patients age, they are less likely to receive the standard of care for stage 1 breast cancer. Even after controlling for other factors, the study showed that failure to adhere to the standards of LN sampling and radiation therapy may have a negative impact in survival.

Role of heat shock proteins in oxygen radical-induced gastric apoptosis.

BACKGROUND: The generation of reactive oxygen species (ROS) and their resultant oxidative damage is a common pathway for gastric mucosal injury. Developing strategies to protect the gastric epithelium against oxygen free radical damage is of profound pathophysiological interest. We have previously shown caspase-mediated apoptosis as a major cause of ROS-induced cell death in gastric mucosa. Because heat shock proteins (Hsps) confer protection against many cytotoxic agents, this study was undertaken to determine whether modulation of Hsps was protective against oxidative damage. MATERIALS AND METHODS: AGS cells (human gastric mucosal cell line) received either no pretreatment, heat shock pretreatment (1 h at 42 ± 1°C), or pretreatment with an Hsp modulating drug (geldanamycin or quercetin). Cells were then exposed to hydrogen peroxide (H2O2), a representative ROS (1 mM, a physiologically relevant concentration), for 24 h. Caspase-3 activation and Poly ADP Ribose Polymerase (PARP) inactivation, as well as DNA-histone complex formation were used as measures of apoptosis. Inducible Hsps (Hsp70 and Hsp90) were detected using Western blot analysis. RESULTS: Results showed heat shock pretreatment induced increased expression of Hsp70 without change in Hsp90. In response to H2O2 exposure alone, there was significant increase in DNA-histone complex formation as well as caspase-3 activation and PARP cleavage in gastric epithelium. Heat shock pretreatment resulted in statistically significant prevention in these measures of apoptosis. Geldanamycin increased Hsp70, but elicited cleavage of Hsp90 and subsequently resulted in an increase in H2O2-induced apoptosis. Quercetin decreased Hsp70 and resulted again in increased H2O2-induced apoptosis. CONCLUSIONS: These findings indicate that heat shock pretreatment protects gastric mucosal cells against H2O2-induced apoptosis and that Hsp70 and Hsp90 may play key roles in this process. These results further suggest that perturbations in Hsp metabolism may induce mucosal injury in response to oxygen free radicals.

Clinical Benefit from Ipilimumab Therapy in Melanoma Patients may be Associated with Serum CTLA4 Levels.

Stage IV metastatic melanoma patients historically have a poor prognosis with 5-10% 5-year survival. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA4), is one of the first treatments to provide beneficial durable responses in advanced melanoma. However, less than 25% of those treated benefit, treatment is expensive, and side effects can be fatal. Since soluble (s) CTLA4 may mediate inhibitory effects previously ascribed to the membrane-bound isoform (mCTLA4), we hypothesized patients benefiting from ipilimumab have higher serum levels of sCTLA4. We found that higher sCTLA4 levels correlated both with response and improved survival in patients treated with ipilimumab in a small patient cohort [patients with (n = 9) and without (n = 5) clinical benefit]. sCTLA4 levels were statistically higher in ipilimumab-treated patients with response to ipilimumab. In contrast, sCTLA4 levels did not correlate with survival in patients who did not receive ipilimumab (n = 11). These preliminary observations provide a previously unrecognized link between serum sCTLA4 levels and response to ipilimumab as well as to improved survival in ipilimumab-treated melanoma patients and a potential mechanism by which ipilimumab functions.

Small bowel carcinoid: Location isn't everything!

AIM: To investigate the prognostic significance of the primary site of disease for small bowel carcinoid (SBC) using a population-based analysis. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for histologically confirmed SBC between the years 1988 and 2009. Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analyses were used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, tumor-node-metastasis stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. RESULTS: Of the 3763 patients, 51.2% were male with a mean age of 62.13 years. Median follow-up was 50 mo. The 10-year OS and DSS for duodenal primaries were significantly better when compared to jejunal and ileal primaries (P = 0.02 and < 0.0001, respectively). On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (P = 0.752 for OS and P = 0.966 DSS) while age, number of primaries, number of LNs examined, T-stage and M-stage were independent predictors of survival. CONCLUSION: This 21-year, population-based study of SBC challenges the concept that location of the primary lesion alone is a significant predictor of survival.

Staging of regional lymph nodes in melanoma: a case for including nonsentinel lymph node positivity in the American Joint Committee on Cancer staging system.

IMPORTANCE: Survival varies widely in patients with stage III melanoma. The existence of clinical significance for positive nonsentinel lymph node (NSLN) status would warrant consideration for incorporation into the American Joint Committee on Cancer staging system and better prediction of survival. OBJECTIVE: To evaluate whether disease limited to sentinel lymph nodes (SLNs) represents different clinical significance than disease spread into NSLNs. DESIGN, SETTING, AND PARTICIPANTS: The database of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, was queried for all patients with SLNs positive for cutaneous melanoma who subsequently underwent completion lymph node dissection. MAIN OUTCOMES AND MEASURES: Disease-free survival, melanoma-specific survival (MSS), and overall survival. RESULTS: A total of 4223 patients underwent SLN biopsy from 1986 to 2012. Of these patients, 329 had a tumor-positive SLN. Of the 329, 250 patients (76.0%) had no additional positive nodes and 79 (24.0%) had a tumor-positive NSLN. Factors predictive of NSLN positivity included older age (P = .04), greater Breslow thickness (P < .001), and ulceration (P < .02). Median overall survival was 178 months for the SLN-only positive group and 42.2 months for the NSLN positive group (5-year overall survival, 72.3% and 46.4%, respectively). Median MSS was not reached for the SLN-only positive group and was 60 months for the NSLN positive group (5-year MSS, 77.8% and 49.5%, respectively). On multivariate analysis, NSLN positivity had a strong association with recurrence (hazard ratio [HR], 1.75; 95% CI, 1.23-2.50; P = .002), shorter overall survival (HR, 2.24; 95% CI, 1.48-3.40; P < .001), and shorter MSS (HR, 2.23; 95% CI, 1.46-3.07; P < .001). To further control for the effects of total positive lymph nodes, comparison was done for patients with only N2 disease (2-3 total positive lymph nodes); the results of this comparison confirmed the independent effect of NSLN status (MSS; P = .04). CONCLUSIONS AND RELEVANCE: Nonsentinel lymph node positivity is one of the most significant prognostic factors in patients with stage III melanoma. Subclassification of melanoma by NSLN tumor status should be considered for the American Joint Committee on Cancer staging system.

AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment?

BACKGROUND: The 7th edition of the AJCC Cancer Staging Manual (AJCC-7) includes substantial changes for colon cancer (CC), which are particularly complex in patients with stage II and III disease. We used a national cancer database to determine if these changes improved prediction of survival. STUDY DESIGN: The database of the Surveillance, Epidemiology and End Results Program was queried to identify patients with pathologically confirmed stage I to III CC diagnosed between 1988 and 2008. Colon cancer was staged by the 6(th) edition of the AJCC Cancer Staging Manual (AJCC-6) and then restaged by AJCC-7. Five-year disease-specific survival and overall survival were compared. RESULTS: After all exclusion criteria were applied, AJCC-6 and AJCC-7 staging was possible in 157,588 patients (68.9%). Bowker's test of symmetry showed that the number of patients per substage was different for AJCC-6 and AJCC-7 (p < 0.001). The Akaike information criteria comparison showed superior fit with the AJCC-7 model (p < 0.001). However, although AJCC-7 staging yielded a progressive decrease in disease-specific survival and overall survival of patients with stage IIA (86.3% and 72.4%, respectively), IIB (79.4% and 63.2%, respectively), and IIC (64.9% and 54.6%, respectively) CC, disease-specific survival and overall survival of patients with stage IIIA disease increased (89% and 79%, respectively). Subset analysis of patients with >12 lymph nodes examined did not affect this observation. CONCLUSIONS: The AJCC-7 staging of CC does not address all survival discrepancies, regardless of the number of lymph nodes examined. Consideration of other prognostic factors is critical for decisions about therapy, particularly for patients with stage II CC.

A 21-year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

OBJECTIVES: Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Cox's regression analyses. RESULTS: Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013). CONCLUSIONS: In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.

Are community hospitals meeting the same standards as academic hospitals for the multimodal management of rectal cancer?

Although multimodal treatment (surgery, chemotherapy±radiation) has improved survival in patients with rectal cancer, there are inconsistent treatment patterns in hospitals in the United States. The objective of the study was to evaluate whether treatment paradigms have changed for patients with Stage II and III rectal cancer in community hospitals compared with academic research hospitals, i.e., teaching or comprehensive hospitals engaged in research. The National Cancer Database was queried to identify all patients diagnosed with Stage II or III rectal adenocarcinoma between 2000 and 2008. The first course of treatment and patient clinicodemographic factors were evaluated. Of 70,409 patients in the study cohort, 7,235 (62.9%) at community hospitals, 24,465 (66.9%) at comprehensive hospitals, and 14,868 (66.6%) at teaching hospitals received multimodal therapy. Community hospitals were more likely to treat individuals who were older, white, and with lower income compared with the other facility types. Teaching hospitals treated a higher proportion of uninsured patients. Despite differences in patient demographics, community hospitals have increased the use of multimodal treatment for rectal cancer but continue to remain below academic research hospital standards.

Surgery for distant melanoma metastasis.

Traditionally, distant metastatic melanoma has a poor prognosis owing to lack of efficacious, U.S. Food and Drug Administration-approved systemic therapy and the limited use of surgical resection as a therapeutic option. More recently, new biological therapies such as vemurafenib (Zelboraf) and ipilimumab (Yervoy) have shown strong promise and dramatically improved the landscape of stage IV melanoma therapy. Although there are numerous single-institution studies advocating the role for therapeutic surgical intervention, many remain skeptical of nonpalliative surgery for metastatic melanoma. Surgical resection of advanced melanoma has been proven to be effective as long as all disease is removed (R0). Patient selection is paramount. The combination of newer systemic therapies and surgical resection is currently under investigation. Understanding the tumor biology of melanoma and its mechanism of metastatic spread is essential to developing the most efficacious treatment strategy.

Effects of surgical excision on survival of patients with stage IV breast cancer.

BACKGROUND: Non-palliative resection of the primary tumor in stage IV breast cancer is controversial. Our aim was to determine whether surgery improves survival in stage IV patients. METHODS: We reviewed records of all stage IV breast cancer patients (1990-2000) at our institution. Data collection included demographics, metastasis sites, treatment, and survival. Survival was compared between metastasis type, hormonal therapy versus no hormonal therapy, chemotherapy versus no chemotherapy, radiation versus no radiation, and surgery versus no surgery. To ascertain local therapy effects while accounting for chemotherapy, we analyzed survival among chemotherapy alone versus chemotherapy with radiation versus chemotherapy with surgery. We also performed multivariate analysis by multiple linear regression. RESULTS: Of 157 patients, 58 (37%) had bone-only metastases, 99 (63%) had visceral metastases. Both groups had a 17-mo median survival. Eighty (51%) received hormonal therapy while 77 (49%) did not. Both groups had a 15-mo median survival. Eighty-four (54%) received chemotherapy with a 25-mo median survival versus 8 mo for 73 (46%) not receiving chemotherapy, Wilcoxon (P < 0.0001), and log-rank (P = 0.02). Fifty-eight (37%) received radiation and 99 (63%) did not, with both groups having a 17-mo median survival. Fifty-two (33%) with surgery to the breast primary had a 25-mo median survival, while 105 (67%) without surgery had a 13-mo median survival, Wilcoxon (P = 0.004) and log-rank (P = 0.06). Among patients receiving chemotherapy, 37 with chemotherapy alone had a 21-mo median survival versus 40 mo for the 14 with chemotherapy and radiation and 22 mo for the 33 with chemotherapy and surgery. These differences were not significant by Wilcoxon (P = 0.41) or log-rank (P = 0.36). Multivariate analysis determined chemotherapy as the only factor associated with improved survival (P = 0.02). CONCLUSION: Our data, when standardized for chemotherapy, suggests loco-regional therapy does not improve survival.

Predictors of length of stay following colorectal resection for neoplasms in 183 Veterans Affairs patients.

BACKGROUND: There is increasing pressure to reduce the length of stay in hospital (LOS) after colorectal surgery. The aim of this study was to identify factors that prolong LOS after colorectal surgery in a population of veterans. METHODS: Retrospective analysis was performed of all patients undergoing colorectal resection for a neoplasm at a single Veterans Affairs (VA) hospital (2002-2007). Data collected included demographics, co-morbidities, operative management, postoperative morbidity and mortality, nutritional status, and LOS. Statistical analysis included descriptive statistics, univariate analysis, and multivariate analysis. RESULTS: A total of 186 patients were identified. Three patients had an LOS of more than 100 days and were omitted from the analysis. The median LOS was 8 days. Multivariate analysis showed only two variables: coronary artery disease (CAD) and postoperative complications were predictive of prolonged LOS. Chronic obstructive pulmonary disease (COPD) was the only preoperative morbidity predictive of complications. CONCLUSIONS: The aim of this study was to identify factors that prolong LOS after colorectal surgery in a VA population. We found that CAD and postoperative complications were the only variables predictive of prolonged LOS after colorectal resection, and COPD was the only factor predictive of postoperative complications.