Low-grade Appendiceal Neoplasm Research Articles

ASO Visual Abstract: Treatment Variation and Long-Term Outcomes of Low-Grade Appendiceal Neoplasms.

ASO Visual Abstract: Treatment Variation and Long-Term Outcomes of Low-Grade Appendiceal Neoplasms.

Treatment Variation and Long-Term Outcomes of Low-Grade Appendiceal Neoplasms.

Heterogenous nomenclature describing appendiceal neoplasms has added to uncertainty around their appropriate treatment. Although a recent consensus has established the term low-grade appendiceal neoplasm (LAMN), we hypothesize that significant variation remains in the treatment of LAMNs. We retrospectively reviewed our prospectively maintained appendiceal registry, identifying patients with LAMNs from 2009 to 2019. We assessed variability in treatment, including whether patients underwent colectomy, spread of disease at presentation, and long-term outcomes. Of 136 patients with LAMNs, 88 (35%) presented with localized disease and 48 (35%) with disseminated peritoneal disease. Median follow-up was 2.9 years (IQR 1.9-4.4), and 120 (88%) patients underwent pre-referral surgery. Among 26 pre-referral colectomy patients, 23 (88%) were performed for perceived oncologic need/nodal evaluation; no nodal metastases were identified. In patients with resected LAMNs without radiographic evidence of disseminated disease, 41 (47%) underwent second look diagnostic laparoscopy (DL) to evaluate for occult metastases. No peritoneal metastases were identified. Patients with disseminated disease were treated with cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC). For patients undergoing CRS/HIPEC, 5-year recurrence-free survival was 94% (95% CI 81-98%). For patients with localized disease, 5-year RFS was 98% (95% CI 85-99%). Significant variation exists in treatment patterns for LAMNs, particularly prior to referral to a high-volume center. Patients frequently underwent colectomy without apparent oncologic benefit. In the current era of high-quality cross sectional imaging, routine use of DL has low yield and is not recommended. Recurrence in this population is rare, and low-intensity surveillance can be offered. Overall prognosis is excellent, even with peritoneal disease.

Intraoperative predictors of appendiceal abnormalities in patients with mucinous ovarian neoplasms.

To evaluate intraoperative factors predicting appendiceal pathology during gynecologic oncology surgery for suspected mucinous ovarian neoplasms. We conducted a retrospective study on 225 patients with mucinous ovarian neoplasms who underwent surgery for an adnexal mass with concurrent appendectomy between 2000 and 2018. Regression analyses were used to evaluate intraoperative factors, such as frozen section of the ovarian mass and surgeon's impression of the appendix in predicting appendiceal pathology. Most patients (77.8%) had a normal appendix on final pathology. Abnormal appendix cases (n = 26) included: metastasis from high-grade adenocarcinoma of the ovary (n = 1), neuroendocrine tumor of the appendix (n = 4), and low-grade appendiceal mucinous neoplasms (n = 26; 23 associated with a mucinous ovarian adenocarcinoma, 2 with a benign mucinous ovarian cystadenoma, and 1 with a borderline mucinous ovarian tumor). Combining normal intraoperative appearance of the appendix with benign or borderline frozen section yielded a negative predictive value of 85.1%, with 14.9% of patients being misclassified, and 6.0% having a neuroendocrine tumor or low-grade appendiceal neoplasm. Benign or borderline frozen section of an ovarian mucinous neoplasm and normal appearing appendix have limited predictive value for appendiceal pathology. Appendectomy with removal of the mesoappendix should be considered in all cases of mucinous ovarian neoplasm, regardless of intraoperative findings.

Use of distinct molecular signatures of appendiceal cancer subtypes to assess biomarker development.

189 Background: Appendiceal Neoplasms are diverse entities which have a variety of clinical presentations, histologic subtypes, biologic behavior, and patient outcomes. Advanced disease at initial diagnosis is not uncommon and therapeutic options are limited. This study aims to identify potential targets to develop epigenetics-based therapeutics/biomarkers. Methods: Archival (FFPE) specimens were collected from 25 patients with histologically confirmed and subtyped appendiceal neoplasia and 16 age-matched non-neoplastic controls. Four appendiceal neoplastic processes identified: Low grade appendiceal neoplasm (LAMN), pseudomyxoma peritonei (intra-peritoneal spread of LAMN), conventional-type adenocarcinoma and goblet cell adenocarcinoma. Gene expression profiling was performed using the HTG EdgeSeq Oncology Biomarker panel. Differentially expressed genes (DEGs) were selected with cut-off threshold FDR<0.05 and analyzed using Qlucore Explorer and functional analyses via Ingenuity Pathway Analysis (IPA). Results: Four appendiceal neoplastic processes identified: pseudomyxoma peritonei (20%), low-grade appendiceal mucinous neoplasm (24%), adenocarcinoma (24%), and goblet cell adenocarcinoma (32%). Unsupervised hierarchical clustering identified 498 DEGs (424 up, 74 down) between all appendiceal cancer versus age-matched controls that showed enrichment in B-cell inflammatory signaling, senescence, cell cycle regulation, PI3K/AKT signaling, cell cycle checkpoint control pathways, and sets relating to NANOG in stem cell pluripotency (all p0.001). G1/S checkpoint, apoptosis, ATM, and PTEN signaling are downregulated (p0.001). TP53, E2F1, IL6, IFNG, TNF, and HGF (p0.001) regulated overlapping genes. Four-subgroups comparison found 67 DEGs involved in T-helper cell differentiation, immune-mediated apoptosis, T-cell fatigue, and PD1/PDL1 signaling to be dysregulated (p0.001). IFNG, FGF2, POU5F1, TNF, and MYC (p0.001) were upstream regulators. Conclusions: In this study, downregulated gene expressions in appendiceal cancers are related to cell proliferation and death control mechanisms, with a trend towards overexpression of inflammatory and cell cycle pathways. It is postulated that genes involved in these pathways are hypermethylated. More research is being undertaken on epigenetics-based biomarkers for diagnosis and prognosis. Given PI’s decades of experience in biomarker research, we aim to develop a "single blood test" to expand bedside monitoring alternatives that align with the National Cancer Moonshot Initiative to discover cancer early, when the likelihood of a cure is highest.

Selection Factors for Treatment and Stratification of Rare Abdominal or Pelvic Tumors with Peritoneal Metastases.

To maximize the results of treatments for peritoneal metastases for rare abdominal or pelvic tumors, selection of patients with a possibility for long-term success is necessary. Because these malignancies are rare, data from which these selection factors can be extracted do not exist. In order to facilitate knowledgeable patient selection for treatment, the well established clinical and histopathologic features of the common malignancies treated for peritoneal metastases were reviewed. The potential application of selection factors for common diagnoses was explored in an attempt to provide selection factors for rare tumors. The histopathologic grade, the lymph node status, the Ki-67 proliferation index, prior surgical score (PSS), preoperative radiologic imaging, preoperative laparoscopic assessment, response to neoadjuvant chemotherapy, peritoneal cancer index (PCI), and completeness of cytoreduction score were all included in this search for relevant selection factors for a rare disease. To facilitate the use of selection factors from common peritoneal metastases diagnoses, these diseases were divided into four groups. Placement of the rare cause of peritoneal metastases into one of these four groups will allow knowledgeable selection for treatment. Rare diseases with a natural history resembling low-grade appendiceal neoplasms are in group 1, diseases resembling lymph node negative colorectal cancer are in group 2, diseases resembling lymph node positive colorectal peritoneal metastases in group 3, and diseases resembling gastric cancer in group 4.

Impact of Macroscopic Tumour Consistency and EPIC in Low-grade Appendiceal Neoplasms With Pseudomyxoma Peritonei

Background/Aim: Low-grade appendiceal mucinous neoplasm (LAMN) with pseudomyxoma peritonei (PMP), otherwise known as disseminated peritoneal adenomucinosis (DPAM), is treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early postoperative intraperitoneal chemotherapy (EPIC). These tumours can vary significantly intraoperatively in terms of macroscopic appearance and consistency, and this may have an effect on survival outcomes. This study examines the differences between soft and hard tumours in terms of shortterm outcomes and long-term survival and whether this can change with the use of EPIC. Patients and Methods: Patients were classified into having macroscopically soft or hard tumours. A comparison of short-term outcomes (major morbidity, mortality, length of ICU stay and length of hospital stay) and long-term outcomes (overall survival) was performed. Survival sub analysis was performed in the patients who received EPIC. Results: Soft tumours behaved differently, with lower morbidity, mortality, shorter ICU stay and hospitalisation. They also demonstrated greater overall survival (86.7% at 5 years, p<0.001). EPIC improved the overall survival for both soft and hard tumours. Conclusion: Tumour consistency has an impact on the outcomes of patients with DPAM and this can be used for prognostication.

Utility of hyperthermic intraperitoneal chemotherapy in cases of incomplete cytoreductive surgery.

Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions. Retrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score. A total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS-HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS-HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low-grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS-HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC. HIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low-grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).

Incidence, Risk Factors, and Outcomes from Conversion of Low-Grade to High-Grade Appendiceal Neoplasms for Patients Undergoing Multiple Cytoreductive Surgeries with Hyperthermic Intraperitoneal Chemotherapy

Conversion from low-grade to high-grade disease is known to occur following repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC); however, the incidence rate, risk factors, and outcomes have not been studied. We conducted a retrospective review of multiple CRS/HIPEC cases for patients originally diagnosed with low-grade appendiceal neoplasms, and compared converted cases with non-converters. Primary outcomes were the incidence rate and risk factors for conversion, while secondary outcomes were effect on cytoreduction, overall survival (OS), and disease-free survival (DFS). Overall, 65 patients undergoing 134 cases of repeat CRS/HIPEC were identified; 11 patients converted to high-grade disease, an incidence rate of 16.92%. Converted cases averaged 4.4 years between CRS/HIPEC, versus 3.7 years for non-converters. Elevated baseline carcinoembryonic antigen (CEA) level, splenectomy at index CRS/HIPEC, and adjuvant chemotherapy utilization were statistically significant with conversion. Conversion had no impact on specific cytoreductive scores at repeat CRS/HIPEC (p=0.435). Evaluating the effect on OS from the index CRS/HIPEC conversion had no impact. Mean OS was 9.5 and 8.8 years for cases that remained low-grade compared with those that converted, respectively (p=0.668); however, when comparing OS from the time of conversion at repeat CRS/HIPEC, patients who progressed to high-grade disease had decreased survival at 4.4 versus 5.8 years (p=0.0317). There was no difference in DFS between non-converters and converters at 4.1 and 3.6 years, respectively (p=0.671). Conversion had no impact on OS from the index CRS/HIPEC but resulted in inferior survival from repeat surgery. Conversion was insignificant in regard to DFS, and should not be considered a contraindication to repeat CRS/HIPEC. Adjuvant chemotherapy should be avoided.

Histopathologic study of Mucinous lesions of the appendix

Mucinous lesions of appendix are rare with an incidence of about 0.2 to 0.7% of all the appendicetomy specimens. The mucinous lesions of appendix range from simple retention cyst to malignant mucinous adenocarcinoma. Majority of mucinous appendiceal neoplasia are epithelial type (70%) with circumferential involvement of mucosa. Peritoneal seeding and pseudomyxoma peritonei can occur with both frankly malignant as well as low-grade appendiceal neoplasms. Nearly 50% of appendiceal malignancies present clinically as acute appendicitis and can be detected by imaging modalities. Aim of this study is to analyse the incidence, age and sex prediliction, clinical presentation and histopathology of mucinous lesions of appendix. It is a reterospective study of all the mucinous lesions of appendix diagnosed at Dept. of Pathology, Kamineni Academy of Medical Sciences and Reserch Centre (KAMSRC) from 2013-2017. Clinical details and relevant radiological investigations are noted from case sheets. Microscopic examination is done on slides stained with routine H &amp; E and AB-PAS. Diagnosis and classification is based on WHO 2010 and recommendations in the AJCC 8th edition. Mucinous lesions accounted for 0.8% (10/1200). of all appendicetomy specimens. The study included 10 cases of mucinous lesions of appendix(10 cases): Simple mucocele (2 cases), Benign mucinous adenomas(3 cases), Low grade Appendiceal Mucinous Neoplasm (LAMN) with pseudomyxoma peritoni (PMP) (1 case), Mucinous cystadeno carcinomas (4 cases). Benign lesions are seen in females and at a younger age as compared to malignancies which are common in males and at a older age. Most common presentation is abdominal pain followed by appendicitis. Mucosal hyperplasia and high grade appendiceal mucinous neoplasms(HAMN) are not seen in our study. Mucinous lesions of appendix are rare. They are more common in females and associated with non-specific clinical features. Histopathology is critical for establishing diagnosis, further management and prognostication of all the mucinous lesions of appendix.

Co-Occurrence of Submucosal Schwannoma and Low-Grade Mucinous Neoplasm in the Appendix, a Clinical Conundrum : A Case Report

Two and more types of tumors rarely occur in the appendix, a constrained space of the human body. We experienced a rare co-occurrence of schwannoma and low-grade mucinous neoplasm (LAMN) in the appendix and obtained a lesson to scrutinize the radiological images in the follow-up period. A computer tomography (CT) performed for surveillance of bile duct stone of a 68-year-old man incidentally detected the appendiceal tumor, which characteristics were not clear at that time, 1-year before admission because of epigastric pain due to acute cholecystitis. CT showed enlargement of tumor in the appendix, and laparoscopic ileocecal resection and cholecystectomy were performed under the diagnosis of acute cholecystectomy and appendiceal tumor. Histopathological examination revealed two types of appendiceal tumors, schwannoma and low-grade appendiceal neoplasm. To the best of our knowledge, co-occurrence of schwannoma and LAMN has never been reported and this complicated our interpretation of clinical images during the course. We report a clinical lesson in handling this rare combination of tumors in the appendix with the relevant literature.

Laparoscopic hyperthermic intraperitoneal chemotherapy for appendiceal tumors.

The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low-grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence. Three patients with LAMN previously treated outside our department were selected for second-look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10-mm trocars were inserted-one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m2 and cisplatin 90 mg/m2 for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow-up of 36 months, all patients were asymptomatic with no evidence of recurrence. Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

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. 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). 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 ≥ 40U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2ng/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. 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.

Goblet Cell Carcinoma Coexisting with Low-Grade Appendiceal Neoplasm of the Appendix

Goblet Cell Carcinoma Coexisting with Low-Grade Appendiceal Neoplasm of the Appendix

Mucinous appendiceal neoplasms: pathologic classification, clinical implications, imaging spectrum and mimics

Mucinous appendiceal neoplasms are uncommon, but important to recognize with imaging due to malignant potential. Peritoneal seeding and pseudomyxoma peritonei can occur with both frankly malignant as well as low-grade appendiceal neoplasms. Prospective imaging identification of potential appendiceal neoplasm is paramount to clinical/surgical management. When a mucinous appendiceal neoplasm is suspected, a right hemicolectomy with lymph node dissection is the preferred surgical management. Unfortunately, accurate preoperative diagnosis can be challenging due to a wide range of clinical presentations and overlapping imaging appearances of appendiceal neoplasms with benign entities. Using the 2010 World Health Organization (WHO) pathologic classification as a framework, we provide a comprehensive multi-modality pictorial essay detailing the broad array of imaging findings of mucinous appendiceal neoplasms and common imaging mimics.

Pseudomyxoma peritonei due to low-grade appendiceal mucinous neoplasm with symptoms of inguinal hernia and uterine prolapse: a case report and review of the literature

Pseudomyxoma peritonei (PMP) is an unusual condition in which massive amounts of mucinous ascites in conjunction with mucinous peritoneal and omental implants occur. We herein report a case of PMP due to low-grade appendiceal neoplasm (LAMN) and a literature review to clarify the clinical features of PMP. A 68-year-old female suffered from anorexia and abdominal distension and was referred to the emergency department of our hospital. Right-side inguinal hernia and uterine prolapse were revealed by a physical examination. Abdominal computed tomography at admission indicated massive ascites and a ruptured cystic mass in the lower-right abdomen. We diagnosed the patient with a ruptured appendiceal mucinous adenoma and PMP and scheduled a laparotomy. We performed an appendectomy containing the cystic mass, bilateral oophorectomy, and a biopsy for the peritoneum. We irrigated the abdominal cavity using 3000 ml of dextran solution. The macroscopic findings showed a ruptured cystic mass measuring 5 × 4 cm arising from the middle of the appendix. The bilateral ovaries and peritoneum were also covered with yellow mucin. The pathologic findings revealed the presence of low-grade atypical cells inside the capsule. However, no tumor cells were found on the surface of the ovary or peritoneum. A literature review revealed that the prognosis of PMP due to LAMN is relatively good, with a 5-year survival rate of 80%, and hernia is occasionally caused by PMP. According to this literature review, we knew this case might be a typical case. However, PMP is very rare; we need further follow-up data to select an optimal treatment for preventing the relapse of PMP.

Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms

Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for preventing peritoneal carcinomatosis in high-risk patients. We report our initial experience with prophylactic HIPEC in a series of patients with appendiceal neoplasms. Methods We retrospectively reviewed our prospectively maintained database to identify patients who underwent HIPEC in the absence of peritoneal disease. Patients with previously documented peritoneal surface disease were excluded. Data regarding clinical, operative and pathological features were analysed. Results Out of 322 HIPEC procedures performed between March 2007and August 2015, we identified 16 patients who underwent surgery with prophylactic intent. Primary diagnoses included high-grade and low-grade appendiceal neoplasms. Most patients presented originally with appendiceal perforation; all patients underwent initial surgery during which the appendix or right colon were resected. Following a median time interval of 2.2 months, a second surgery performed at our institution consisted of completion of omentectomy, partial colectomy and oophorectomy, with administration of prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was attempted and achieved in 11 patients in whom the median duration of surgery, estimated intraoperative blood loss and length of hospitalisation were 251 min, 100 cm3 and 4 days, respectively. There were no cases of major perioperative morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms is feasible, safe and may be performed laparoscopically. Larger studies with long-term follow-up are needed to determine whether a survival benefit is associated with this treatment.

The Role of Heated Intraperitoneal Chemotherapy (HIPEC) in Low-Grade Appendiceal Neoplasm: Friend or Foe?

Low-grade mucinous appendiceal neoplasms are rare tumors. There is limited data on the treatment for pseudomyxoma peritonei with low-grade appendiceal histology. Classifications of appendiceal neoplasms include low-grade appendiceal mucinous neoplasm (LAMN), diffuse peritoneal adenomucinosis (DPAM), and peritoneal mucinous carcinomatosis (PMCA). Studies have demonstrated patients with low-grade appendiceal neoplasms have improved overall survival compared to patients with high-grade appendiceal neoplasms. Since low-grade tumors have better prognosis some retrospective trials have suggested observation in patients with these types of tumors. Another option includes cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). We have done an extensive literature search exploring the various methods in which to treat patients with this disease.

Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Outcomes from a single tertiary center

BackgroundMultivisceral resection as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) may be required in order to achieve optimal debulking. This study aimed to assess perioperative and long-term outcomes of the most extensive CRS/HIPEC procedures. MethodsAll patients who underwent CRS/HIPEC at our institution between March 2007 and July 2014 were retrospectively reviewed. Patients undergoing extreme cytoreduction (n = 50), defined as a resection of ≥5 organs or ≥3 bowel anastomoses, were compared with patients who underwent less extensive procedures (n = 219). ResultsComplete cytoreduction (CC score ≤1) was achieved in 76% of the extreme CRS/HIPEC group, which included patients with colorectal cancer (CRC, n = 17), appendiceal adenocarcinoma (n = 20), gastric cancer (n = 6), and low-grade appendiceal neoplasm (n = 3). When compared with other patients undergoing CRS/HIPEC, the extreme CRS/HIPEC group had higher median PCI score, increased intraoperative blood loss, longer duration of surgery and longer hospital stay (all p values < 0.001). Major 30-day morbidity was significantly higher among the extreme CRS/HIPEC group (34% vs. 17.4%, p = 0.008) and there was also a trend towards higher 90-day mortality (12% vs. 5.1%, p = 0.07). Median disease free survival and overall survival in CRC patients undergoing extreme CRS/HIPEC was poorer (4.1 vs. 14.3 months, p = 0.01 and 10.1 vs. 43.8 months, p < 0.001, respectively). Extreme CRS/HIPEC was found to independently predict decreased overall survival in CRC patients. ConclusionsExtreme multivisceral resection as part of CRS/HIPEC is associated with higher major morbidity and inferior oncologic outcomes; therefore CRS/HIPEC provides the best outcomes in patients with fewer organs involved.

Is there a role for neoadjuvant chemotherapy in the management of non-carcinoid epithelial neoplasms of the appendix?

15115 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) are considered the standard of care for patients with pseudomyxoma peritonei (PMP) and carcinomatosis of appendiceal origin. The role of neoadjuvant chemotherapy (CTX) in the management of these patients is unknown. Methods: Retrospective analysis of all patients evaluated for the treatment of appendiceal epithelial neoplasms at a tertiary center between 1992 and August 2006. All diagnoses were confirmed pathologically and classified by a single group of pathologists. Patients with carcinoid tumors or metastases to the appendix were excluded. Tumor histology, stage, peritoneal-based disease, and the potential for complete cytoreduction dictated treatment. Results: 250 consecutive patients were evaluated, 140 of whom had low grade disease. 114 underwent CRS and HIPEC. Median follow-up was 24 mos from referral. Average time to referral was 13 mos after diagnosis (range 0–243); 85% had undergone prior surgical therapy (median 1.3 operations, range 1–4); 22% had previous CTX consisting of many different regimens. 5- and 10-year survival for patients with low grade tumors treated with CRS and HIPEC alone (n=80) were 84% and 68%, respectively. 21 patients with low grade tumors had CTX prior to CRS and HIPEC. There was no effect on overall survival (p = 0.61). 5-and 10-year survival of 39 patients with low grade histology who did not receive CRS and HIPEC was 55% and 30%, respectively (p = 0.009). 83 patients with intermediate and high-grade disease who received CTX but not CRS and HIPEC had a 5- year survival of 27%. 5-year survival for patients with intermediate or high grade disease who underwent CRS and HIPEC (n=13) was 67%. Conclusions: Patients with peritoneal-based disease from non-carcinoid epithelial neoplasms of the appendix who undergo CRS and HIPEC have a more favorable survival. Currently there is no survival advantage to the use of CTX before CRS and HIPEC for low grade appendiceal neoplasms. The role of neoadjuvant CTX and biologic agents for patients with high grade neoplasms needs to be determined. Early referral to a peritoneal malignancy center will help standardized treatment for these patients. No significant financial relationships to disclose.