Search

Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

In addition to severe, life-limiting complications such as malignant bowel obstruction, fistulae, and malignant ascites, peritoneal carcinomatosis frequently causes life-impacting symptoms such as pain, nausea, anorexia, cachexia, and fatigue. A variety of medical, interventional, and surgical therapies are now available for management of both complications and symptoms. Although surgery in this population is often associated with a relatively high risk of morbidity and mortality, operative intervention can offer effective palliative treatment in appropriately selected patients. Early involvement of palliative care specialists as part of a multidisciplinary team is essential to providing optimal, holistic care of patients with peritoneal carcinomatosis.

Management of intra-articular calcaneal fractures remains a debated topic in orthopaedics, with operative fixation often held in reserve due to concerns regarding perioperative morbidity and potential complications. The purpose of this study was to identify the characteristics of patients who developed surgical complications to inform the future stratification of patients best suited to operative treatment for intra-articular calcaneal fractures. All patients who underwent open reduction and internal fixation of calcaneal fractures utilizing the Sinus Tarsi approach between March 2014 and July 2018 were identified using theatre records. Patient imaging was used to assess pre- and post-operative fracture geometry with Computed Tomography (CT) used for pre-operative planning. Each patient's clinical presentation was established through retrospective analysis of medical records. Patients provided verbal consent to participation and patient reported outcome measures were recorded using the Maryland Foot Score. Fifty-eight intra-articular calcaneal fractures (fifty-three patients; five bilateral, mean age = 46.91 years) with a mean follow up of 35.4 months (6 – 57) were included. Five patients (9.4%) had wound complications; two superficial (3.7%), three deep (5.6%); four of whom were smokers. Smokers were statistically more likely to have wound infections than non-smokers (p=0.04). Intra-articular fractures of the calcaneus should be considered for surgical intervention in order to improve long-term functional outcomes. The Sinus Tarsi approach provides the potential to decrease the operative complication rate whilst maintaining adequate fixation, however, the decision to surgically manage these fractures should be carefully balanced against the risk of post-operative complications. This increased risk of complication associated with smoking may tip the balance against benefit from surgical management.

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients.Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD.The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P 0.001).Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

Gas forming infection (GFI) of the spine is a rapidly progressive and potentially life-threatening infection. It can be a consequence of aetiologies such as Emphysematous Osteomyelitis (EOM), Necrotizing Fasciitis (NF), and Gas-containing Spinal Epidural Abscess (Gas-containing SEA). This review aims to summarize the characteristics of these subtypes of GFI, describing their aetiology, diagnosis, management, and prognosis. PubMed, Embase, Web of Science and the Cochrane Database were systematically searched for studies reporting on gas forming infections of the spine or a known subtype. Cases of post-operative and iatrogenic spinal infection were excluded. The literature review revealed 35 studies reporting on 28 cases of EOM, three cases of NF involving the spine and seven cases of Gas-containing SEA. Thirty studies reporting on 32 cases of GFI were available for data analysis. The mean age of the patients was 60.9 years and a concomitant diagnosis of diabetes mellitus was reported in 57.5% of patients infected. Fever and back pain were the most common presenting symptoms. The lumbar spine was the most commonly affected spinal segment. Mortality from EOM, NF and Gas-containing SEA were 34.8, 100 and 28.5%, respectively. Gas forming infection of the spine is a rare condition with an extremely poor prognosis, requiring early and aggressive surgical treatment. A multi-disciplinary approach is necessary for management. Nonetheless, even in cases of early recognition and optimal management, multisystem failure may still occur, and mortality rates remain high due to the aggressive nature of this infection. Systematic review of level IV studies.

CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). The US HIPEC collaborative database (2000–2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. A total of 174 patients were identified. Median PCI was 16 (3–39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59–4.74; MOR-2+ : HR 0.77, 95% CI 0.22–2.69). MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan–Meier and Cox estimates were used to assess survival. In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of desmoplastic small round cell tumor, breast, and gastrointestinal stromal tumor specifically related to peritoneal surface malignancy. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction.Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations.A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P .001; colorectal: r = 0.729; P .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071).In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

We investigated the feasibility of utilizing an exon skipping approach as a genotype-dependent therapeutic for neurofibromatosis type 1 (NF1) by determining which NF1 exons might be skipped while maintaining neurofibromin function. Human neurofibromin is well-known as a GTPase activating protein (GAP), but outside of its GAP-related domain (GRD), it is unclear how critical other regions are for function. Initial in silico analysis predicted exons that can be skipped with minimal loss of neurofibromin function. Utilizing a novel Nf1 cDNA system, we performed a functional screen to determine the effects of exon skipping on in vitro neurofibromin expression and GRD function. Loss of single exons 12, 17, 25, 41, 47, or 52 maintained significant GRD function in at least two Ras activity assays. Exons 18/19, 20 and 28 are critical for GRD function; deletion of exons 20, 41, or 47 led to significantly lower levels of neurofibromin. As suggested by in silico analysis, skipping of exons 17 or 52 resulted in both the highest neurofibromin levels and the greatest suppression of Ras activity. Assessment of NF1 patient databases indicates that pathogenic variants resulting in deletion or skipping of exons 17, 25, and 52 have not been reported; and truncating pathogenic variants in each exon account for ~0.91, 0.94, and 0.25% of unrelated NF1 cases, respectively. Hence, we designed antisense phosphodiamitate morpholino oligos (PMOs) to skip exon 17 and evaluated them in human cell lines that we generated via CRISPR/Cas9 with a patient-specific truncating pathogenic variant, c.1885G>A. We down-selected oligos that efficiently caused skipping of exon 17 and restored NF1 expression and function. Further, homozygous deletion of exon 17 in a novel mouse model is compatible with viable and grossly healthy animals with normal lifespan and no tumor development, providing proof-of-concept that exon 17 is not essential for murine neurofibromin function. Mild phenotypes observed include abnormal nesting behavior and lymphoid hyperplasia with increased numbers of both B- and T-cells. Hence, exon skipping should be further investigated as a therapeutic approach for NF1 patients with treatment of individuals with pathogenic variants in exon 17.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (&lt, 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

The eighth edition of American Joint Committee on Cancer (AJCC) advocates a 3-tier grading system for appendiceal mucinous tumors. The mutational profile for each tumor grade and the impact of TP53 mutation on survival are unknown. We classified appendiceal mucinous tumors into 3 grades based on the eighth edition of American Joint Committee on Cancer: 21 G1 low-grade mucinous neoplasms, 21 G2 appendiceal adenocarcinomas, and 26 G3 signet ring cell carcinomas. Mutation profiles were obtained using next-generation sequencing. The impact of TP53 on prognosis was investigated by multivariable analysis. Most G1 tumors harbor KRAS/GNAS mutations with TP53 and SMAD4 in a small subset of cases. G2 and G3 tumors show a more complex mutation pattern carrying PIK3CA, BRAF, or TP53 mutations in addition to KRAS/GNAS. PTEN mutations were detected exclusively in G2 tumors. The prevalence of KRAS and GNAS mutations is significantly lower in G3 tumors relative to G1/G2, whereas TP53, PIK3CA, or BRAF mutations are common. Mutations in NRAS, IDH2, CDH1, RB1, CTNNB1, CDKN2A, PTPN11, and KIT genes were observed in single cases. Patients with TP53-mutated disseminated G2 and G3 tumors had worse progression-free survival than did those with wild-type TP53 tumors (P = .0315). A trend toward worse overall survival was observed in TP53-mutated G3 tumors (P = .102). p53 expression correlated with mutation status. We demonstrate a distinct but overlapping pattern of gene mutations in each grade of appendiceal mucinous tumors and the independent impact of TP53 mutation on progression-free survival but not overall survival.

Osteoarthritis is believed to be the final common pathway in a variety of disturbances to joint metabolism. Cartilage damage may signify one of the first steps in this pathway. Biomarkers in cartilage damage and early osteoarthritis could potentially classify patients into clinical phenotypes for the prediction of the clinical course and facilitate personalised precision treatment.

Background Moral distress is common among healthcare providers, leading to staff burnout and attrition. This study aimed to identify root causes of and potential solutions to moral distress experienced by surgical intensive care unit (SICU) providers. Materials and methods This is a mixed methods study of physicians and nurses from a single, academic SICU. We obtained quantitative data from the Measures of Moral Distress for Healthcare Professionals (MMD-HP) survey and qualitative data from semi-structured interviews. The MMD-HP is a 27 question, validated survey on triggers of moral distress. Survey and interview data were analyzed to identify drivers of moral distress using a convergent design. Results 21 nurses and 25 physicians were surveyed and 17 providers interviewed. MMD-HP data demonstrated high levels of moral distress for nurses (mean total MMD-HP 132 ± 63.5) and physicians (121.7 ± 64.7), P = 0.68. The most frequent root cause of moral distress for all providers was participating in the delivery of aggressive care perceived to be futile. Nurses also reported caring for patients with unclear goals of care as a key driver of moral distress. Interview data supported these findings. Providers recommended improving access to palliative care to increase early communication on patient goals of care and end-of-life as a solution. Culture in the SICU often promotes supporting aggressive care however, acting as a potential barrier to increasing palliative resources. Conclusions Providing aggressive care that is perceived as futile was the primary driver of moral distress in the SICU. Interventions to improve early communication and access to end-of-life care should be prioritized to decrease moral distress in staff.

BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on thesurvivalof patients withappendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.MethodsThe US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsOf the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major operation frequently necessitating red blood cell transfusion. Using multi-institutional data from the U.S. HIPEC Collaborative, this study sought to determine the association of perioperative allogenic blood transfusion (PABT) with perioperative outcomes after CRS/HIPEC. This retrospective cohort study analyzed patients who underwent CRS/HIPEC for peritoneal surface malignancy between 2000 and 2017. Propensity score-matching was performed to mitigate bias. Univariate analysis was used to compare demographic, preoperative, intraoperative, and postoperative variables. Factors independently associated with PABT were identified using multivariate analysis. The inclusion criteria were met by 1717 patients, 510 (29.7%) of whom required PABT. The mean Peritoneal Cancer Index (PCI) of our cohort was 14.8 ± 9.3. Propensity score-matching showed an independent association between PABT and postoperative risk of pleural effusion, hemorrhage, pulmonary embolism, enteric fistula formation, Clavien-Dindo grades 3 and 4 morbidity, longer hospital stay, and reoperation (all P

Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. CA19-9 [HR 2.44, CI 1.2–3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06–23.46] was independently predictive of OS (p

BackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p

Despite significant recent advances in the management of peritoneal carcinomatosis, this diagnosis still is accompanied frequently by a grim survival prognosis, often measured in weeks to months. The poor prognosis also is accompanied often by complications and symptoms that have a dramatic impact on quality of life and are challenging to the managing health care provider and devastating to loved ones caring for the person who is suffering. Consequently, management of carcinomatosis often revolves around palliation of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia as well as emotional and existential concerns. This article reviews several palliative treatment options for some of the more common symptoms and complications associated with advanced, incurable peritoneal carcinomatosis. Although readers should recognize that carcinomatosis is no longer an imminent death sentence, providers caring for patients with peritoneal carcinomatosis also must be well-versed in the palliative management of this condition and recognize the utility of early palliative care referral in this setting.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of peritoneal mesothelioma. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness of the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

BACKGROUND. No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS. The U.S. HIPEC Collaborative database (2000–2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6–12mos or high-frequency surveillance (HFS) at q2–4mos. Primary outcome was overall survival (OS). RESULTS. Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for noninvasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two postoperative years would potentially save $13–19 M/year to the U.S. healthcare system. CONCLUSIONS. Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Hyperthermia enhances the cytotoxicity of chemotherapeutic agents used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). However, this may result in an elevated core body temperature (CBT), with unintended effects on surgical morbidity. This study evaluates the relationship of maximum CBT during CRS/HIPEC on postoperative outcomes. A retrospective review of patients undergoing CRS/HIPEC from January 2011 to July 2017 was performed. Outcomes were stratified according to maximum CBT reached during HIPEC. Primary study endpoints were 30-day morbidity and 30-day complication severity. Overall, 135 consecutive CRS/HIPEC cases were reviewed; 36 (27%) had a maximum CBT ≥ 39.5 °C during the 90-min HIPEC. CBT ≥ 39.5 °C was associated with an increase in 30-day postoperative complications (58% vs. 34%, p = 0.01) and severe Clavien–Dindo grade III or higher complications (22% vs. 11%, p = 0.04). On multivariate analysis, the adjusted odds ratio of having any complication was 3.77 (95% confidence interval [CI] 1.56–9.14) and a Clavien–Dindo grade III or higher complication was 3.46 (95% CI 1.10–10.95) when maximum CBT reached 39.5 °C. Flow rates ≥ 2.35 L/min were associated with lower average CBT (p = 0.05) and improved peritoneal heating (p = 0.02). Maximum CBT ≥ 39.5 °C is associated with an increased risk of postoperative morbidity. Higher flow rates are associated with improved intraperitoneal heating, lower CBT, and may contribute to optimizing the therapeutic benefit of HIPEC.

Background For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. Methods All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). Results Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. Conclusion The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

Background and Objectives Lymphatic mapping (LM) and blue dye injections are essential to identification of sentinel lymph nodes (SLN) for melanoma. LM is performed the day before (DB) or the same day (SD) of surgery, but the optimal timing is unknown. Similarly, methylene blue (MB), used during SLN biopsy (SLNB), is administered diluted (dMB) or undiluted (uMB), but the relative efficacies are unknown. Methods Patients who underwent SLNB for melanoma from 2009 to 2013 at our institution were evaluated. Outcomes included operative correlation with LM, SLN identification, and postoperative complications. Results One hundred seventy-one patients underwent SLNB. Sixty-seven (39%) had DB LM. Sixty-seven (39%) received uMB. Operative findings correlated with both LM groups, though the DB patients had lower background count (P = 0.018) and lower highest SLN radioactive signal count (P = 0.046). More uMB patients had blue SLNs (90% vs. 68%, P = 0.001). There was no difference in the total number of SLNs or complication rates in the LM and MB groups. Conclusions This is the first study to compare the use of DB LM with SD LM and the efficacy of uMB versus dMB. DB LM and uMB offer advantageous alternatives for patients and their surgeons without loss of accuracy or increased morbidity. J. Surg. Oncol. 2016;114:947–950. © 2016 Wiley Periodicals, Inc.

PURPOSE: The ColoCare Study is an international cohort of men and women (>18 years age) newly diagnosed with stage I-IV colorectal cancer from seven centers in the United States and Germany. Study enrollment is currently ongoing. Here, we describe the clinical and demographic characteristics of this large cohort of prospectively followed colorectal cancer patients and describe differences in demographic, lifestyle, and clinical characteristics by age of onset and tumor site. METHODS: Data on demographics (sex, age, race, ethnicity) and lifestyle factors (smoking, body mass index) collected at baseline are included in this analysis, in addition to information on tumor characteristics (tumor stage and site), treatment (neoadjuvant and adjuvant therapy), and clinical outcomes (vital status, recurrence). Patients were categorized into early- ( RESULTS: Data on 1,933 stage I-IV colorectal cancer cases were included in this study, 19% of which were deceased at the time of this analysis. On average, patients were 60 years old, had a BMI of 29 kg/m2, and were predominantly diagnosed with stage II (25%) and stage III (33%) colorectal cancer. Fifty three percent of cases were diagnosed with colon cancer, while 47% were rectal cancer cases. Twenty percent (n=364) of patients were diagnosed before age 50 (i.e. early-onset cases). The early-onset group presented with a higher percentage of rectal cancer (52%) and more advanced disease (64% stage III-IV cancer) compared to late-onset cases (46% and 48%, respectively). Percentages of ever smokers were higher among late-onset compared to early-onset patients (51% vs. 38%), independent of tumor site. Early-onset cancers were more likely to originate in the rectum compared to colon, particularly among women (61% vs. 51%). Early-onset rectal cancer cases were more likely to be female as compared to late-onset rectal cancer cases (61% vs. 36%). Corresponding with national trends, early-onset cases received more aggressive adjuvant therapy after surgical resection compared to late-onset patients (54% vs. 40%). DISCUSSION: Within this large international multi-center cohort, patients with early-onset colorectal cancer were more likely to be diagnosed with rectal cancer and advanced stage disease. The majority of early-onset cases in the ColoCare Study were non-smokers. As expected, more aggressive treatment modalities were used in patients with early-onset disease. Citation Format: Caroline Himbert, Jane Figueiredo, Lyen Huang, Biljana Gigic, Courtney L. Scaife, Bartley Pickron, Laura Lambert, Jessica Cohan, Mary Bronner, Jolanta Jedrzkiewicz, Esther Herpel, Matthias Kloor, Johanna Nattenmueller, Hans-Ulrich Kauczor, Alexis Ulrich, Seth Felder, Julian Sanchez, Sophie Dessureault, Nathan Hinkle, Justin Monroe, Matthew Mutch, Cory Bernadt, Deyali Chatterjee, Mika Sinanan, Stacey Cohen, Ulrik Wallin, Deepti Reddi, Mukta Krane, Afshin E. Gabayan, David M. Hoffman, Yosef Y. Nasseri, Robert W. Decker, Karen Zaghiyan, Zuri A. Murrell, Andrew E. Hendifar, Jun Gong, Eiman Firoozmand, Alexandra Gangi, Beth A. Moore, Kyle G. Cologne, Maryliza El-Masry, William Grady, Martin Schneider, Stephanie L. Schmit, Erin Siegel, David Shibata, Adetunji Toriola, Christopher Li, Cornelia Ulrich, Sheetal Hardikar. Clinical characteristics and outcomes of colorectal cancer in the ColoCare Study: Differences by age of onset [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2364.

Until recently, a diagnosis of peritoneal carcinomatosis was uniformly accompanied by a grim prognosis that was typically measured in weeks to months. Consequently, the management of carcinomatosis revolves largely around palliation of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia. A prior lack of effective treatment options created the nihilistic view that currently exists and persists despite improvements in the efficacy of systemic therapy and the evolution of multimodality approaches including surgery and intraperitoneal chemotherapy. This article reviews the evolution and current state of treatment options for patients with peritoneal carcinomatosis. In addition, it highlights recent advances in understanding the molecular biology of carcinomatosis and the focus of current and future clinical trials. Finally, this article provides practical management options for the palliation of common complications of carcinomatosis. It is hoped that the reader will recognize that carcinomatosis is no longer an imminent death sentence and that through continued research and therapeutic innovation, clinicians can make an even greater impact on this form of metastatic cancer.

The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC.A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests.Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin.This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Cancer recurrence after complete resection of the primary tumor is dreaded by patients and physicians alike. Intensive follow-up after curative resection is considered a marker of good practice and frequently perceived as an antidote against recurrence by patients and families. In the United States, there is abiding faith in frequent imaging and blood tests as the best tools for the job. Thoughtful practice, clinical guidelines, retrospective reviews of prospectively gathered data, and clinical trials of follow-up have focused on the number, frequency, and sequence of modalities. A different perspective on which to predicate follow-up of patients with curatively treated cancer is to consider whether meaningful treatment options exist for recurrence. In cancers for which there are meaningful treatment options, it is reasonable to expect that moreintensive follow-up may improve survival. This commentary discusses this perspective in the context of the established literature in patients with colorectal and breast cancers, two cancers considered to have effective treatments for metastatic and recurrent disease as compared with non–small-cell lung cancer (NSCLC) and pancreatic cancer, which do not.

BACKGROUND: Appendiceal neoplasms include tumors ranging from benign-appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery. METHODS: A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit. RESULTS: Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received ≥2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4-11) and 56 months (95% CI, 36-not applicable), respectively. CONCLUSIONS: Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists. Cancer 2010. © 2010 American Cancer Society.

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS. Methods All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC)

Background Although completion lymph node dissection (CLND) is the standard of care for breast cancer patients with sentinel lymph node (SLN) metastases, the SLN is the only node with tumor in 40% to 60% of cases. To assist with decision-making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center devised and validated a nomogram for predicting the likelihood of non-SLN metastases. To assess the generalizable use of this nomogram, validation analysis was performed by using an external database.

Background Peritoneal dissemination of cancer is a terminal condition with limited therapeutic options. Because the peritoneal cavity is a single enclosed space, regional treatment approaches for isolated peritoneal cancrinomatosis are appealing. There is a potential role for gene therapy in the management of peritoneal cancrinomatosis. Materials and methods An adenoviral construct of the human p14ARF gene (a tumor suppressor) and a 22 amino acid sequence of the ARF gene product, which has cell membrane penetrating properties, were assayed for proapoptotic properties in a human colorectal cancer cell line (Clone A) cells in vitro . Peritoneal carcinomatosis derived from Clone A cells was also established in nude mice and then treated with intraperitoneal administration of an adenoviral construct of the human p14ARF gene. Results Treatment of ARF-negative Clone A cells with Ad-hARF in vitro reestablished ARF function. However, the cell penetrating ARF-related peptide did not restore ARF function in Clone A cells. Treatment of Clone A peritoneal xenografts with a single intraperitoneal dose of Ad-hARF (9 × 10 6 viral particles) suppressed the progression of peritoneal disease. Weekly (six times) administration of the Ad-hARF at a lower dose (3 × 10 6 viral particles) also suppressed tumor progression. Conclusions Treatment of peritoneal carcinomatosis by intraperitoneal administration of adenoviral constructs of inactivated tumor suppressor genes may be a feasible clinical approach, and ARF may represent a suitable molecular target for tumors where the ARF gene is inactivated.

For most patients with biliary cancer effective treatment options are limited, side effects are common, and the long-term prognosis is grim. A majority of biliary cancer patients are diagnosed with advanced-stage cancer. Many have comorbidities that preclude major hepatic surgery, and it is estimated that up to 25 % of patients who are considered surgical candidates after a thorough preoperative work-up are unable to undergo a complete surgical resection. Of those who do undergo curative resection, 5-year survival is less than 50%. Patients with metastatic disease have limited chemotherapy options and on average survive only 3–6 months. Given the poor prognoses of biliary tract and gallbladder cancers, it is important that caregivers are educated on symptom management and palliation for this patient population.

Poorly differentiated and signet ring cell adenocarcinomas of the appendix represent a subset with aggressive tumor biology and poor outcomes with few studies evaluating the impact of systemic chemotherapy and cytoreductive surgery (CRS).A retrospective chart review of patients with either poorly differentiated and signet ring cell appendiceal adenocarcinomas was completed from 1992 to 2010.One hundred forty-two patients were identified. Seventy-eight patients with metastatic disease received chemotherapy. Radiographic response was 44%, median progression-free survival (PFS) was 6.9 months, and median overall survival (OS) was 1.7 years. In multivariate analysis, response to chemotherapy [hazard ratio (HR) 0.5; P = 0.02] predicted improved PFS, and complete CRS (HR 0.3; P = 0.004) predicted improved OS. Patients who underwent complete CRS (n = 26) had a median relapse-free survival (RFS) of 1.2 years and a median OS of 4.2 years. In multivariate analysis for this subset, complete cytoreduction score of 0 was significantly correlated with improved RFS (HR 0.07; P = 0.01) and OS (HR 0.02; P = 0.01).Systemic chemotherapy appears to be a viable treatment option for patients with metastatic poorly differentiated and signet ring cell appendiceal adenocarcinomas. Complete CRS is associated with improved RFS and OS, though part of this benefit likely reflects the selection of good tumor biology.

Multicystic peritoneal mesothelioma (MCPM) is a rare cystic proliferation most often seen in women of reproductive age with a history of prior abdominal surgery. This is a case report of an 83-year-old woman diagnosed with MCPM during an exploratory laparotomy for presumed peritoneal carcinomatosis from colon cancer. After complete removal of all visible MCPM, the patient remains free of both colon cancer and MCPM. This article reviews the literature with regards to the pathology, natural history, risk of malignant transformation, and current options for management of MCPM, including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Deregulation of the G1 cyclin, cyclin E, has been shown to be both the most powerful predictor of prognosis in early stage breast cancer as well as a significant determinant of tumor aggressiveness.1,2 It may also contribute to treatment failure due to chemoresistance. Because some form of cell cycle deregulation is present in all malignant cells,3 increasing understanding of these processes is starting to provide new opportunities to overcome the cells’ resistance mechanisms.

Pseudomyxoma peritonei (PMP) is a poorly understood disease characterized by mucinous ascites and disseminated peritoneal mucinous tumors, with a clinically protracted course. Although PMP has been ascribed to a variety of sources (Yasar et al. 1997; Lee and Scully 2000; Imaoka et al. 2006), clinical and molecular evidence is mounting that neoplastic mucin-producing goblet cells of the appendix are the primary cause of PMP. (Ronnett et al. 1995; Ronnett et al. 1997; Szych et al. 1999). Although PMP is not an intrinsically malignant process, it is not a benign process either. Not only does PMP replace the entire free space of the abdomen with mucin, it also causes fibrosis that often leads to complete bowel obstruction and ultimately death. Currently the only effective treatment for PMP is cytoreductive surgery (CRS) that removes all of the mucin and mucin-producing cells combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (Sugarbaker 2006).

Hypothesis Three-gland parathyroidectomy with transcervical thymectomy and cryopreservation is the preferred initial surgical approach for hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1. Design Retrospective cohort study. Setting Tertiary referral center. Patients Thirty-seven patients with multiple endocrine neoplasia type 1 who underwent 1 or more surgical procedures for HPT from January 1, 1973, to April 30, 2004. Results At initial parathyroid surgery, 16 (43%) of 37 patients had fewer than 3 parathyroid glands resected (group 1); 16 (43%), had at least 3 but fewer than 4 glands (group 2); and 5 (14%), 4 or more glands (group 3). Follow-up of at least 6 months after initial surgery was complete for 31 (84%) of 37 patients. Recurrent HPT developed in 20 (65%) of 31 at a median of 4 years. Reoperation for recurrent HPT was performed in 16 (52%) of 31, including 12 patients (75%) in group 1 and 4 (25%) in group 2. No patient in group 3 required reoperative cervical surgery. Permanent hypoparathyroidism occurred in 1 patient (3%), despite autograft of parathyroid tissue to the forearm. Conclusions Recurrent HPT in patients with multiple endocrine neoplasia type 1 is frequent if fewer than 3 glands are removed at initial parathyroidectomy. Optimal surgical intervention must balance the risk of recurrent hypercalcemia with the morbidity of permanent hypoparathyroidism. Three-gland parathyroidectomy, transcervical thymectomy, and parathyroid cryopreservation constitute our preferred initial surgical procedure.

Hypothesis Interval reevaluation for resectability of hepatic colorectal metastases aids patient selection. Design A retrospective review. Setting A tertiary care medical center. Patients and Methods From January 1, 1985, to July 1, 1998, 318 patients with colorectal hepatic metastases were identified. Resectable lesions (N=73) were divided into synchronous (n=36) or metachronous (n=37) and retrospectively reviewed for immediate resection or interval reevaluation. Kaplan-Meier survival curves of treatment groups were compared by the log-rank test. Results Survival curves of patients with synchronous and metachronous lesions undergoing interval reevaluation vs immediate resection were not significantly different ( P =.74 and P =.65, respectively). No lesions from patients who underwent interval reevaluation became unresectable due to growth of the initial metastases. After interval reevaluation, 8 (29%) of 28 patients with synchronous metastases were spared the morbidity of laparotomy because of distant or an increased number of metastases and 10 (36%) of 28 patients were spared the morbidity of hepatic resection at the time of interval laparotomy. Actuarial median and 5-year survival of patients after delayed hepatic resection (51 months and 45%, respectively) were significantly improved compared with those of all other patients with resectable metastases (23 months and 7%, respectively) ( P =.02). For patients with metachronous lesions who underwent interval reevaluation, 4 (29%) of 14 patients were spared the morbidity of laparotomy because of an increased number of hepatic or distant metastases. Conclusions Delaying hepatic resection for metastatic colorectal cancer does not impair survival. Potentially, two thirds of patients can avoid major hepatic surgery. For synchronous metastases, delaying hepatic resection appears to select patients who will benefit from hepatic resection.

Importance The role of interval appendectomy after conservative management of perforated appendicitis remains controversial. Determining the etiology of perforated appendicitis is one reason to perform interval appendectomies. Objective To determine whether adult patients undergoing interval appendectomy experience an increased rate of neoplasms. Design Retrospective study. Setting A single tertiary care institution. Participants All patients 18 years or older who underwent appendectomy for presumed appendicitis from January 1, 2006, through December 31, 2010. Exposures Appendectomy for presumed appendicitis. Main Outcomes and Measures Underlying neoplasm as the cause of presentation for presumed appendicitis. Demographic data, clinicopathologic characteristics, interval resection rate, and complication data were collected and analyzed. Results During the study period, 376 patients underwent appendectomies. Interval appendectomy was performed in 17 patients (4.5%). Neoplasms were identified in 14 patients (3.7%); 5 of those tumors occurred in patients who had undergone interval appendectomy (29.4%). Nine neoplasms were mucinous tumors (64.3%), including all neoplasms associated with interval appendectomies. The mean age of all patients with appendiceal tumors was 49 years (range, 35-74 years). Conclusions and Relevance Mucinous neoplasms of the appendix were found in 5 of 17 patients (29.4%) undergoing interval appendectomy. Interval appendectomies should be considered in all adult patients, especially those 40 years or older, to determine the underlying cause of appendicitis. A multi-institutional study to determine the generalizability of these findings is warranted.

406 Background: Well-differentiated appendiceal adenocarcinomas (WDAA) are rare tumors characterized by peritoneal spread. Lymph node metastasis can occur, yet the association between nodal spread and recurrence is poorly understood. Methods: A single institution retrospective review of patients seen between August 1993 and January 2010 with a pathologic diagnosis of WDAA who underwent colectomy was conducted. Patients with zero lymph nodes found during pathologic review were excluded. Parameters evaluated included demographics, presence of lymph node metastasis, completeness of cytoreduction and time to recurrence. Results: Of 688 patients with appendiceal neoplasms, 160 (23.3%) had WDAA. The mean age at diagnosis was 50.7 years and 81 (50.6%) were male. Median follow-up after diagnosis was 58.5 months. One hundred patients (62.5%) had regional or distant metastasis present at the time of colectomy. Seventy-eight (48.8%) colectomies were performed at outside institutions. The median number of nodes examined was 12. Twelve patients (7.5%) were found to have nodal metastasis. The rate of peritoneal metastasis did not correlate with the presence of nodal metastasis (node positive 9/12, 75% versus node negative 91/148, 61.5%; p=0.35). No difference in the ability to perform complete cytoreduction existed for those with and without nodal metastasis (66% versus 51% p=0.19). Examining patients with complete cytoreduction and ≥ 12 months of follow-up, there was an increased risk of recurrence among patients with lymphatic metastasis compared to those without (5/8, 62.5% versus 15/61, 24.6%; p=0.03). In this subset, median disease-free-survival in lymph node positive patients was 53 months compared to 109.1 months in patients without nodal metastasis (p=0.08). Conclusions: Patients with WDAA tumors have an overall favorable prognosis; however, patients with lymph node metastasis appear to have an increased risk of recurrence and apparent shortened disease free survival. Right colectomy may be warranted in this patient population.

430 Background: The role of interval appendectomy after conservative management of perforated appendicitis remains controversial. Determining the etiology of perforated appendicitis is one reason to perform interval appendectomies. This study hypothesizes that there is an increased rate of neoplasm in patients undergoing interval appendectomy. Methods: This is a retrospective review of all patients over 18 years of age who underwent appendectomy for presumed appendicitis from January, 2006 to December, 2010 at a single, tertiary care institution. Demographic data, pathologic diagnosis, clinico-pathologic characteristics, interval resection rate, and complication data were collected and analyzed. Results: During the study period, 376 patients underwent appendectomy. The mean age was 41 years (range 18 to 94). Interval appendectomy was performed in 18 patients (5.0%) (age 28 to 74). Neoplasms were identified in 14 patients (3.7 %); 6 were found in patients who had undergone interval appendectomy (33%). Nine were mucinous tumors (69.2%), 5 of which were associated with interval appendectomies. Neoplasms were identified in 8.3% of patients between 35 and 55 years old. Conclusions: Mucinous neoplasms of the appendix were found in 33% of patients undergoing interval appendectomy. Interval appendectomies should be considered in all patients 35 years and older due to increased risk of appendiceal neoplasm. [Table: see text]

Background Delivery of large doses of local anesthetics for spinal anesthesia by repeated injections or continuous infusion could expose the cauda equina to concentrations of drug that may be neurotoxic per se. We studied this possible neurotoxic effect by assessing recovery from conduction blockade of desheathed peripheral nerves after exposure to some of the local anesthetic solutions commonly used for spinal anesthesia. Methods The reversibility of conduction blockade was studied in desheathed bullfrog sciatic nerves, using the sucrose-gap method for recording compound action potentials, before and during exposure to local anesthetics and during drug washout. The nerves were exposed for 15 min to 5% or 1.5% lidocaine, with or without 7.5% dextrose; 0.5% tetracaine; or 0.75% bupivacaine (the latter two without dextrose). Some nerves were also bathed in 7.5% dextrose (without local anesthetic) or in 0.06% tetracaine, which in this preparation is equipotent to 5% lidocaine. After 15 min in the drug, the nerves were washed for 2-3 h and soaked in Ringer's solution overnight. Nerves exposed only to Ringer's solution served as controls. We also studied neuronal uptake and washout of radiolabeled lidocaine. Results Exposure of nerves to 5% lidocaine, with or without 7.5% dextrose, or to 0.5% tetracaine resulted in irreversible total conduction blockade, whereas 1.5% lidocaine or 0.75% bupivacaine caused 25-50% residual block after the 2-3 h wash. Nerves exposed to Ringer's solution, 7.5% dextrose or 0.06% tetracaine had 0-10% residual block after 2-3 h wash. The action potential of all nerves declined after overnight soak to between 30-60% of the control value, except for those nerves exposed to 5% lidocaine or 0.5% tetracaine, which showed no activity. Exposure to 5% lidocaine for periods of only 4-5 min produced total, irreversible loss of conduction. The uptake by and washout of radiolabeled lidocaine from the nerves indicate that the maximum amount of residual drug after 2-4 min of exposure to 5% lidocaine and a 3-h wash should cause at most only 50% conduction block. Conclusions Solutions of 5% lidocaine and 0.5% tetracaine that have been associated with clinical cases of cauda equina syndrome after continuous spinal anesthesia caused irreversible conduction block in desheathed amphibian nerve. Whether these in vitro actions also occur in mammalian nerves in vivo is an important, clinically relevant question now under investigation in our laboratory.

OBJECTIVE To evaluate the effect of surgical resection and radiotherapy (RT) in retroperitoneal or abdominal sarcoma. DESIGN Retrospective cohort. SETTING Surveillance, Epidemiology, and End Results, 1988-2005. PATIENTS Patients 18 years or older with initial diagnosis of primary retroperitoneal and nonvisceral abdominal sarcoma. MAIN OUTCOME MEASURES Survival for 2 years after diagnosis. Kaplan-Meier survival was stratified based on surgery and RT status. Cox proportional hazards model was used to assess adjusted effects of surgery and RT on survival in patients with locoregional disease. RESULTS Of 1901 patients with locoregional disease, 1547 (81.8%) underwent resection; 447 (23.5%) received RT. Overall, patients who received both surgery and RT demonstrated improved survival compared with patients who underwent either therapy alone; patients undergoing monotherapy in turn had more favorable survival compared with patients who received neither therapy (P < .001, log rank). Cox analysis demonstrated that surgical resection (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.21-0.29; P < .001) and RT (0.78; 0.63-0.95; P = .01) independently predicted improved survival in locoregional disease only. In adjusted analyses stratified for American Joint Commission on Cancer (AJCC) stage, for stage I disease (n = 694), RT provided an additional benefit (HR, 0.49; 95% CI, 0.25-0.96; P = .04) independent of that from resection (0.35; 0.21-0.58; P < .001). For stage II/III (n = 552), resection remained protective (HR, 0.24; 95% CI, 0.18-0.32; P < .001); however, RT was no longer associated with a significant benefit (0.78; 0.58-1.06; P = .11). CONCLUSIONS In a national cohort of retroperitoneal and abdominal sarcomas, surgical resection was associated with significant survival benefits for AJCC disease stages I to III. Radiotherapy provided additional benefit for patients with stage I disease. Resection should be offered to reasonable surgical candidates with nonmetastatic retroperitoneal/abdominal sarcomas; radiotherapy may most benefit patients with early-stage disease.