Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei.

BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Mortality risk prediction for primary appendiceal cancer.

BACKGROUND: Accurately predicting survival in patients with cancer is crucial for both clinical decision-making and patient counseling. The primary aim of this study was to generate the first machine-learning algorithm to predict the risk of mortality following the diagnosis of an appendiceal neoplasm. METHODS: Patients with primary appendiceal cancer in the Surveillance, Epidemiology, and End Results database from 2000 to 2019 were included. Patient demographics, tumor characteristics, and survival data were extracted from the Surveillance, Epidemiology, and End Results database. Extreme gradient boost, random forest, neural network, and logistic regression machine learning models were employed to predict 1-, 5-, and 10-year mortality. After algorithm validation, the best-performance model was used to develop a patient-specific web-based risk prediction model. RESULTS: A total of 16,579 patients were included in the study, with 13,262 in the training group (80%) and 3,317 in the validation group (20%). Extreme gradient boost exhibited the highest prediction accuracy for 1-, 5-, and 10-year mortality, with the 10-year model exhibiting the maximum area under the curve (0.909 [±0.006]) after 10-fold cross-validation. Variables that significantly influenced the predictive ability of the model were disease grade, malignant carcinoid histology, incidence of positive regional lymph nodes, number of nodes harvested, and presence of distant disease. CONCLUSION: Here, we report the development and validation of a novel prognostic prediction model for patients with appendiceal neoplasms of numerous histologic subtypes that incorporate a vast array of patient, surgical, and pathologic variables. By using machine learning, we achieved an excellent predictive accuracy that was superior to that of previous nomograms.

Celecoxib and Myrtol: A Novel Therapy for Recurrent Appendiceal Mucinous Neoplasms With Extensive Peritoneal Dissemination.

BACKGROUND: Unresectable appendiceal mucinous neoplasms (AMNs) with extensive peritoneal dissemination cause significant morbidity and have limited treatment options. We evaluated a novel combination of Celecoxib and Myrtol in treating such AMNs. METHODS: Patients with recurrent AMNs with extensive peritoneal disease treated with a daily regimen of 200 mg Celecoxib and 1200 mg Myrtol Standardized were included. Progression-free survival (PFS) and overall survival (OS) were calculated, and carcinoembryonic antigen (CEA) trends were compared pretreatment and post-treatment in terms of percentage change. RESULTS: Thirteen patients with extensive, recurrent disease (median peritoneal carcinomatosis index of 36) were included between 2017 and 2020. The median age was 63 years (interquartile range: 55 to 67) and 7 (54%) were male. A total of 85% had undergone prior cytoreductive surgery while 15% underwent cytoreductive surgery >2 times. 54% had received multiple cycles of systemic chemotherapy before starting Celecoxib-Myrtol. After a median follow-up of 8 months, median PFS and OS were 16 months (interquartile range: 5 to 17) and 27 months, respectively. Nine (69.2%) showed improvement in CEA values 3 months after treatment compared with 3-month pretreatment CEA trends. None had adverse events attributable to Celecoxib-Myrtol. CONCLUSIONS: Our feasibility study suggests that a regimen of Celecoxib-Myrtol is well tolerated and may prolong PFS and OS in patients with recurrent AMNs with peritoneal spread.

Peritoneal Spread of Low-grade Appendiceal Tumours - 2 Days of Early Postoperative Intra-peritoneal Chemotherapy Are Enough.

BACKGROUND/AIM: While controversial, cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) and early postoperative intra-peritoneal chemotherapy (EPIC) remains the mainstay of treatment for low grade appendiceal neoplasm with pseudomyxoma peritonei (PMP). Our study aimed to investigate the difference in survival when administering HIPEC alone vs. HIPEC + EPIC. Additionally, we examined whether the duration of EPIC affects survival. PATIENTS AND METHODS: We compared the difference in survival in 238 patients who underwent CRS + HIPEC alone vs. CRS + HIPEC/EPIC combination for low grade appendiceal cancer. We also compared short course (1-2 days) vs. long course (3-5 days) of EPIC. RESULTS: HIPEC/EPIC combination group (n=179) showed a significantly better 5-year survival of 95% compared to 71% in HIPEC alone (n=59). There was no statistically significant difference in 5-year survival between short course (n=22) and long course of EPIC (n=157). CONCLUSION: Combined use of HIPEC and EPIC improves 5-year survival in low-grade appendiceal neoplasm. Two days of EPIC are sufficient.

Nomogram to predict overall survival of patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease, with the rate of overall survival (OS) influenced by many factors. The present study aimed to define independent predictors and establish a nomogram for individual risk prediction in PMP patients. METHODS: One hundred forty-seven PMP patients were consecutively included between June 1, 2013, and November 22, 2019. The log-rank test was used to compare the OS rate between groups; subsequently, variables with p < .10 were subjected to multivariate Cox modeling for defining independent prediction indicators. Finally, a nomogram was established based on independent prognosticators and assessed for internal validation. RESULTS: Multivariate Cox analysis showed that D-dimer level, carbohydrate antigen (CA) 125 level, CA 19-9 level, degree of radical surgery, and histological grade were all independently associated with OS in PMP patients. A nomogram was plotted and underwent internal validation. The discrimination ability of the nomogram revealed a good predictive ability as indicated by the C-index value (0.825), and calibration plots confirmed good consistency between the predicted and observed survival probabilities. CONCLUSIONS: Five independent prognostic factors for predicting the survival of PMP patients were identified, and the nomogram based on these independent indicators showed a reasonable discrimination ability for individual risk prediction.

Twenty-years' experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP).

PURPOSE: Pseudomyxoma peritonei is treated with cytoreductive surgery (CRS) combined and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). The purpose of this study was to report the20-year experience of one surgical team inCRS and HIPEC for PMP of appendiceal origin. METHODS: Retrospective study of the files of patients with PMP of appendiceal origin that underwent CRS+HIPEC. Morbidity and hospital mortality were recorded. Clinical and histopathologic variables were correlated to survival and recurrence. RESULTS: The files of 41 patients with PMP of appendiceal origin that underwent CRS+HIPEC from 1999-2018 were retrieved. The mortality and the morbidity rates were 2.4% and 29.3%, respectively. The 5- and 8-year survival rate was 68.3%. The completeness of cytoreduction, and the extent of previous surgery were identified as the prognostic indicators of survival. The recurrence rate was 32.5% with the completeness of cytoreduction, the histologic type of the tumor being the prognostic indicator. CONCLUSIONS: CRS in combination with perioperative intraperitoneal chemotherapy is a safe and effective treatment in the management of PMP of appendiceal origin.

Comparison of model fit and discriminatory ability of M category as defined by the 7th and 8th editions of the tumor-node-metastasis classification of colorectal cancer and the 9th edition of the Japanese classification.

BACKGROUND: In transitioning from the 7th edition of the tumor-node-metastasis classification (TNM-7) to the 8th edition (TNM-8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC-9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. METHODS: The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. RESULTS: According to TNM-8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC-9) tumors. Among the three classification systems, JPC-9 had the lowest AIC value (JPC-9: 10546.3; TNM-7: 10555.9; TNM-8: 10585.5), highest C-index (JPC-9: 0.608; TNM-7: 0.598; TNM-8: 0.599), and superior time-dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. CONCLUSIONS: While the revised M category definition did not improve model fit and discriminatory ability from TNM-7 to TNM-8, further subdivision of M1c in JPC-9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system.

Women survive longer than men undergoing cytoreductive surgery and HIPEC for appendiceal cancer.

BACKGROUND: We hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men. METHODS: The National Cancer Database (NCDB) public user file (2004-2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed. RESULTS: 1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141-1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006-1.027, p = 0.0017) were both found to be independent risk factors for worse OS. CONCLUSION: Women undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival.

Indications and outcomes for repeat cytoreductive surgery and heated intra-peritoneal chemotherapy in peritoneal surface malignancy.

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS: Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION: Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).

Ki67 does not predict recurrence for low-grade appendiceal mucinous neoplasms with peritoneal dissemination after cytoreductive surgery and HIPEC.

Low-grade appendiceal mucinous neoplasms (LAMN) can disseminate to become low-grade mucinous carcinoma peritonei (LGMCP), which is optimally treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Approximately half of the patients with LGMCP recur despite complete cytoreduction, and risk factors for recurrence are poorly understood. We sought to evaluate if Ki67 predicts progression of LGMCP after CRS/HIPEC. A retrospective review of a prospectively maintained database was performed to identify patients treated with complete CRS/HIPEC for LGMCP from 2008 to 2019 with Ki67 assessed. Patient characteristics, histologic data, average and focally high "hotspot") Ki67 index, progression-free survival (PFS), and overall survival (OS) were analyzed. Ki-67 immunostain was performed on the histologic section with the highest cellularity and architectural complexity. Forty-four patients with LGMCP (55% male, median age 61) were identified. The median Ki67 score and hotspot Ki67 score was 15% (1-70) and 50% (1-90), respectively. On univariate analysis, average Ki67 and hotspot Ki67 were not predictive of PFS when analyzed as continuous normalized values (HR 1.0, p = 0.79 and HR 1.1, p = 0.38, respectively) or as categorical values when stratified by the median (HR 0.9, p = 0.67 and HR 1.0, p = 0.93). This remained true on multivariate analysis when stratified for peritoneal cancer index, CEA, and completeness of cytoreduction score for both normalized Ki67 and hotspot Ki67 (HR 0.9 [95% CI 0.8-1.3], p = 0.94 and HR 1.04 [95% CI 0.8-1.3], p = 0.73, respectively). Ki67 failed to predict disease recurrence for patients with LGMCP in this cohort.

Lymph node positivity and association with long-term survival for different histologies of appendiceal cancer.

BACKGROUND: Appendiceal cancers represent a diverse group of malignancies with varying biological behavior. The significance of lymph node metastases in relation to long-term survival and chemotherapy response is poorly defined. METHODS: The National Cancer Database was queried to find patients diagnosed with appendiceal cancer from 1998 to 2012. Kaplan-Meier curves and multivariable Cox regression analyses were used to study the association between lymph node status and overall survival. Stage IV patients were excluded. RESULTS: The rate of nodal positivity of the 9841 patients with known node status was: signet ring 47.4%, carcinoid 42.3%, nonmucinous adenocarcinoma 28.8%, goblet cell 21.9%, and mucinous adenocarcinoma 20.4%. Node-positive patients had worse long-term survival for all subtypes with the exception of carcinoid tumors (p < 0.001). The strongest association was for signet cell and goblet cell. Adjuvant chemotherapy in node-positive patients improved survival for mucinous, nonmucinous, and signet ring cell histology (p < 0.01), but not for goblet cell. CONCLUSIONS: Nodal involvement in patients with appendiceal cancer varies in incidence, association with adverse survival, and response to systemic therapy. Individualized treatment algorithms for the management of the subtypes of appendiceal cancer are needed.

Can Elderly Patients with Peritoneal Metastasis Induced by Appendiceal or Colorectal Tumours Benefit from Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

PURPOSE: Cytoreductive surgery (CRS) added with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the survival rate of certain patients with peritoneal metastasis (PM). However, the perioperative safety and long-term survival of this intricate and possibly life-threatening procedure in elderly patients (≥65 years) remain controversial. METHODS: Patients with PM due to appendiceal or colorectal tumours who underwent CRS/HIPEC were evaluated systematically at the National Cancer Center of China and the Huanxing Cancer Hospital between June 2017 and June 2019. The recruited subjects were retrospectively categorized into elderly (age ≥65) and non-elderly (age<65) groups according to their age. Clinical and pathological features, postoperative outcomes, and prognoses were gathered and analysed. RESULTS: Both groups had similar overall morbidity (56.0% vs 38.7%, P=0.130) and grade 3/4 morbidity (28.0% vs 20.0%, P=0.403) after CRS/HIPEC. However, more patients in the elderly group suffered from ileus postoperatively (16.0% vs 2.6%, P=0.033). After a follow-up period of a median of 20 months, it was concluded that elderly patients had significantly worse 3-year overall survival (OS) than non-elderly patients (16.3% vs 51.4%, P=0.001). Independent prognostic factors were identified to be a high peritoneal carcinomatosis index (PCI) score (HR, 1.10, 95% CI, 1.04-1.16; P=0.001) and age ≥65 (HR, 2.42, 95% CI, 1.32-4.45; P=0.004) were independent prognostic factors through cox regression analysis. CONCLUSION: CRS and HIPEC are related with an elevated prevalence of postoperative ileus but not with the overall morbidity or the grade 3/4 morbidity in elderly patients. However, since worse survival outcomes were observed more commonly in elderly patients compared to younger patients from CRS+HIPEC, this complex and potentially life-threatening procedure should be considered carefully in patients aged ≥65 years.

Clinicopathological Characteristics of Low-Grade Appendiceal Mucinous Neoplasm.

INTRODUCTION: Recently, "low-grade appendiceal mucinous neoplasms" (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. METHODS: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. RESULTS: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). CONCLUSIONS: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.

Impact of high-risk features for stage II adenocarcinoma of the appendix.

BACKGROUND: Clinico-pathological high-risk features are frequently utilized in adjuvant chemotherapy (AC) decisions in stage II colorectal cancer and their utility in stage II appendiceal adenocarcinoma (AA) is not established. The aim of this study is to determine the impact of high-risk features in clinical outcomes and whether high risk features are predictive of AC benefit in stage II AA. METHODS: Patients with pathological stage II AA between 2010 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8140, 8480 and C18.1. High risk stage II AA was defined as having at least one of the following clinicopathological features: T4 tumor, <12 lymph nodes examined, poorly differentiated histology, positive margins, or lymphovascular invasion. Patients with none of these features were defined as low-risk. RESULTS: A total of 1040 patients with pathological stage II AA were identified. 51.0% males, 84.5% Caucasian; median age 61 (range, 19-90). 46.4% were determined to have high-risk stage II AA. High-risk status was associated with worse OS compared to low-risk in univariate (HR 1.55; 95% CI 1.18-2.02; p = 0.001) and multivariable analyses (HR 1.36; 95% CI 1.03-1.79; p = 0.028). High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients (67.1% vs. 74.5%, p = 0.0013). AC was administered in 34.4% (n = 166) of high-risk patients and in 36.5% (n = 203) of low-risk patients. Among high-risk patients, AC was not associated with better OS in univariate (HR 0.86; 95% CI 0.59-1.26; p = 0.448) and multivariable analyses (HR 1.35; 95% CI 0.90-2.04; p = 0.151) compared to no AC. Similarly, among low-risk patients, AC was not associated with better OS in univariate (HR 0.92; 95% CI 0.60-1.39; p = 0.679) and multivariable analyses (HR 1.27; 95% CI 0.81-2.02; p = 0.299) compared to no AC. For high-risk patients, 5-year OS was 68.3% in patients that received AC vs. 66.5% in patients that did not (p = 0.722). For low-risk patients, 5-year OS was 74.0% in patients that received AC vs. 76.3% in patients that did not (p = 0.813). CONCLUSION: High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients. AC did not improve survival regardless of high-risk features in stage II AA in this retrospective study. A prospective randomized clinical trial would be required to determine the impact of high-risk features on AC in stage II AA.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery.

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. Design, Setting, and Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Main Outcomes and Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules. Conclusions and Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

Appendiceal neoplasm incidence and mortality rates are on the rise in Australia.

OBJECTIVES: The study aimed to examine the incidence and mortality rates of appendiceal neoplasms (ANs) in Australia. METHODS: A retrospective analysis was performed on national data obtained from the Australian Institute of Health and Welfare (AIHW) from 1982 to 2013. Changes to the incidence, and the cancer-specific mortality following the diagnosis of ANs were analyzed over this time period, with stratification performed for histological subtype, gender, and age groups (<50y and ≥50y). RESULTS: Incidence and mortality rates of ANs increased significantly across both genders and age groups. Incidence rates increased by 415%, from 0.40/100 000 population in 1982 to 2.06/100 000 in 2013. Overall mortality rates increased by 130%, from 0.057/100 000 during 1982-1985 to 0.131/100 000 during 2010-2013. Controlling for age group and gender, the incidence rates increased by 20% every four years (Incidence rate ratio (IRR) = 1.20, 95% confidence interval (CI): 1.17, 1.23, global P value<0.0001), and controlling for age, the mortality rates increased by 8% every four years (IRR = 1.08, 95% CI: 1.00, 1.17, global P-value = 0.0401). CONCLUSION: The increasing use of CT scanning, improvements in pathological assessment of the appendix, and the growing aging population may have contributed in part to the apparent rise in the incidence of ANs.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases - The Hong Kong experience and literature review.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief. METHODS: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival. RESULTS: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31). CONCLUSION: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.

Impact of signet ring cells on overall survival in peritoneal disseminated appendix cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: To determine the effect of signet ring cell (SRC) histopathology in appendix cancer with peritoneal dissemination on overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for appendix cancer from April 1999 to December 2019. RESULTS: 255 patients were identified. 174 had high-grade disease with no SRC component, 35 with a low count of SRC and 46 with a high count of SRC. Median OS without SRC was 93.8 months vs 58.2 months for low count SRC and 23.7 months for high count SRC (P < 0.001). 5-year OS was 60% for patients with no SRC, 35.5% and 10% in those with low count and high count SRC respectively. On multivariate analysis, presence of SRC and complete cytoreduction score were identified as independent factors that affect OS. CONCLUSION: The presence of SRC in appendix cancer with peritoneal dissemination is associated with worse OS when compared to an absence of SRC in patients undergoing CRS/HIPEC.

Analysis of Clinicopathological Characteristics of Appendiceal Tumors in Japan: A Multicenter Collaborative Retrospective Clinical Study- A Japanese Nationwide Survey.

BACKGROUND: Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE: This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN: This was a nationwide multi-institution retrospective observational study. SETTING: This study was conducted at the participating tertiary referral hospitals. PATIENTS: Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the total survivability. RESULTS: A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS: This study was limited by its retrospective study design. CONCLUSIONS: We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANÁLISIS DE LAS CARACTERÍSTICAS CLINICOPATOLÓGICAS DE LOS TUMORES APENDICULARES EN JAPÓN: UN ESTUDIO CLÍNICO RETROSPECTIVO COLABORATIVO MULTICÉNTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cáncer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es difícil debido a su rareza.Este estudio tuvo como objetivo investigar las características clinicopatológicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de múltiples instituciones a nivel nacional.Este estudio se realizó en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cáncer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el análisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenían adenocarcinomas mucinosos y 245 (32,2%) tenían adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucínica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 años del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p <0,01). Con respecto al adenocarcinoma mucinoso, el análisis multivariado reveló que el alto grado de diferenciación (Comité Estadounidense Conjunto sobre el Cáncer grado 2/3), las metástasis a distancia y la operación R2 se asociaron significativamente con una mayor tasa de mortalidad a 5 años. La tasa de supervivencia a 5 años fue significativamente mejor para las neoplasias mucinosas apendiculares de bajo grado (93.3%) que para otros adenocarcinomas mucinosos (72,1%) (p <0,01).Este estudio fue limitado por su diseño de estudio retrospectivo.Investigamos acumulativamente los tumores apendiculares en un estudio retrospectivo multicéntrico y este es el primer informe de este tipo de Asia. Agrupar los grados según el Comité Estadounidense Conjunto sobre el Cáncer fue útil como indicador pronóstico de los adenocarcinomas mucinosos apendiculares, incluida la neoplasia mucínica apendicular de bajo grado. Consulte Video Resumen en http://links.lww.com/DCR/B282. (Traducción-Dr. Yesenia Rojas-Khalil).