Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC): Cancer Survivors' Perspective Through In-Depth Interviews.

BACKGROUND: CRS/HIPEC patients face unique quality of life (QoL) challenges due to advanced disease (peritoneal carcinomatosis), the extent of procedure, and risk for long-term complications. Standard QoL questionnaires are generic, focusing on tumor type and standard treatments, and likely do not capture this select population's full experience, suggesting the need for tailored instruments. We aimed to characterize the QoL challenges faced by CRS/HIPEC cancer survivors and determine whether these were captured by a standard QoL questionnaire. PATIENTS AND METHODS: An anonymous, semi-structured individual interview was conducted with CRS/HIPEC patients addressing their experience at diagnosis, challenges related to CRS/HIPEC, and access to CRS/HIPEC information. Verbatim transcripts were interpreted using thematic analysis. Code and theme identification was inductive. Questions addressing common themes that were not encompassed by a standard QoL questionnaire were developed. RESULTS: We interviewed eight patients. Median age was 55 (range 30-71) years and 75% (n = 6) were women. Primary tumor sites included appendix (n = 4), ovarian (n = 3), and peritoneal mesothelioma (n = 1). Median time from CRS/HIPEC was 40.1 (range 3.1-216.3) months. Overall, 133 codes were identified and categorized into 9 themes. The most recurring were physical symptoms after CRS/HIPEC (specifically gastrointestinal symptoms), adjusting to survivorship, mental health, expectations from CRS/HIPEC, and access to care. A total of 22 questions that did not overlap with a standardized QoL questionnaire were developed. CONCLUSIONS: There is an unmet need to understand the unique QoL challenges CRS/HIPEC patients encounter. Patient-centered QoL questionnaires based on CRS/HIPEC patient experiences can capture these unique challenges and help guide future studies and care.

Safety of Nephrectomy Performed During CRS/HIPEC: A Propensity Score-Matched Study.

BACKGROUND: Surgeons may hesitate to perform nephrectomy (NE) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) due to a potential increase in morbidity. However, no data are available regarding the impact of NE on outcomes, so the authors decided to assess its safety during CRS/HIPEC. METHODS: A single-center propensity score-matched study was conducted using a prospective database (1994-2021). The study included patients who underwent NE during CRS/HIPEC with completeness of cytoreduction (CC) of 0, 1, or 2. Control subjects (no-NE) were selected in a 1:3 ratio using propensity score-matching weighted by age, histology, peritoneal cancer index (PCI), CC-0 or CC-1 rate, and length of surgery. RESULTS: Among 828 patients, 13 NE and 39 no-NE control subjects were identified. The indications for NE included tumor involvement of the ureter, hilum, and/or kidney with preserved (n = 8), decreased (n = 2), or absent (n = 3) function. NE patients received more intraoperative intravenous (IV) fluids (16,000 vs 11,500 mL; p = 0.045) and had a greater urine output (3200 vs 1913 mL; p = 0.008). NE patients received mitomycin C (40 mg for 90 min) or melphalan (50 mg/m2 for 90 min) without reduction of dose or time. Major morbidity (p = 0.435) and mortality (p = 1.000) were comparable between the two groups. No postoperative acute kidney injury was seen in either group. Adjuvant chemotherapy was administered to 46.2% of the NE and 35.9% of the no-NE patients (p = 0.553), with similar starting times (p = 0.903) between the groups. CONCLUSIONS: Nephrectomy performed during CRS/HIPEC does not seem to increase postoperative morbidity or to delay adjuvant chemotherapy, and NE can be performed if required for complete cytoreduction. The NE patients in our cohort did not have a reduction of mitomycin C or melphalan dose or perfusion time.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. METHODS: A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). RESULTS: We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). CONCLUSIONS: After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Outcomes Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy with and without Diaphragmatic Resection in Patients with Peritoneal Metastases.

BACKGROUND: Diaphragmatic resection (DR) is often required during cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to achieve complete cytoreduction (CC). While CC provides the best survival, requiring a DR may indicate unfavorable tumor biology. We assessed how DR during CRS/HIPEC affects outcomes. METHODS: A retrospective cohort study was conducted using a prospective single-center database from October 1994-May 2020. Peritoneal surface malignancy patients who underwent CRS/HIPEC with CC-0/1/2 were assigned to DR and NoDR groups. Survival was measured using the Kaplan-Meier method. Subgroup analysis was performed for patients with peritoneal cancer index (PCI) ≥ 20 to eliminate confounding of more extensive disease in DR. RESULTS: Of 824 CRS/HIPECs, 774 were included: 134 DR and 640 NoDR. PCI was significantly higher in DR: 29 versus 21, p < 0.001. CC-0/1 rate was 89% in DR and 95% in NoDR (p = 0.003). Neither 100-day morbidity nor mortality differed between the groups (p = 0.355 and p = 1.000). Median follow-up was 64 months. Median overall survival (OS) was significantly lower in DR (32 vs. 96 months, p < 0.001). Subgroup analysis by tumor type in patients with PCI ≥ 20 showed significantly shorter OS in DR than NoDR in appendiceal (40 vs. 196 months, p < 0.001) and colorectal (14 vs. 23 months, p = 0.003), but not in ovarian tumors (32 vs. 42 months, p = 0.893), whereas median PCI did not differ among subgroups. CONCLUSIONS: DR during CRS/HIPEC does not increase morbidity and mortality. It is associated with worse survival in appendiceal and colorectal tumors, even after adjusting for tumor burden but does not appear to impact ovarian cancer survival.

Iterative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Recurrence after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal tumors (AT) with mucinous carcinomatosis peritonei (MCP) is common. The evidence favoring iterative procedures (iCRS/HIPEC) is limited, and its benefit is not clear for all patients. METHODS: Retrospective (1998-2020) cohorts of AT patients with MCP recurrence after the first CRS/HIPEC were analyzed. Outcomes were compared within tumor grades between iCRS/HIPEC patients and matched control patients without iCRS/HIPEC using propensity score matching (1:1). Post-recurrence survival (PRS) was measured from the date of recurrence after the first CRS/HIPEC to death or last contact. RESULTS: Overall, 55 iCRS/HIPEC patients were identified: 36 low-grade (LGMCP) patients, 13 high-grade (HGMCP) patients, and 6 HGMCP patients with signet-ring features (HGMCP-S). Nine patients had a third CRS/HIPEC. The median peritoneal cancer index (PCI) scores were 33, 19 and 10, with CC-0/1 achieved for 94.4%, 78.2% and 88.9% of the patients after the first, second, and third CRS/HIPEC, respectively. No 90-day postoperative mortality occurred. The median progression-free survival from the first CRS/HIPEC was 19.7 months for the iCRS/HIPEC patients versus 14.2 months for the matched control patients (p = 0.43). The median PRS was 80.2 months for iCRS/HIPEC versus 36.2 for the control patients (p < 0.001). For the iCRS/HIPEC versus the matched control patients, the median PRS by tumor grade was 174.1 versus 51.9 (p < 0.001) for the LGMCP, 42.0 versus 12.4 (p = 0.02) for the HGMCP, and 15.4 versus 8.1 months (p = 0.61) for the HGMCP-S patients, respectively. CONCLUSIONS: Selected low- and high-grade appendiceal cancer patients with MCP recurrence able to undergo iterative CRS/HIPEC procedures showed favorable outcomes and such patients should be considered for surgery when feasible. This survival benefit with iCRS/HIPEC is not evidenced in recurrent MCP with signet ring cell morphology.

Systemic Chemotherapy for High-Grade Mucinous Appendiceal Cancer with Peritoneal Spread After Unsuccessful CRS/HIPEC.

BACKGROUND: The best management of patients who have unresectable mucinous appendiceal cancer (MAC) with peritoneal spread after a failed attempt at cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. This study aimed to assess outcomes after systemic chemotherapy (SCT) for patients with unresectable peritoneal metastases from high-grade MAC. METHODS: A single-center retrospective cohort study was conducted using a prospective CRS/HIPEC database. The study included high-grade MAC patients with peritoneal carcinomatosis who were deemed surgical candidates, but had an aborted CRS/HIPEC or only palliative HIPEC due to unresectable disease. Overall survival (OS) was compared. RESULTS: Of 72 identified patients, 20 received SCT and 52 did not (NoCT). The groups were balanced by age (p = 0.299), sex (p = 0.930), histopathologic subtype (p = 0.096), preoperative chemotherapy (p = 0.981), and postoperative major complication rates (p = 0.338). Both groups had extensive disease (median peritoneal cancer index at exploration, 39 vs 39). The median number of cycles was 12 (interquartile range [IQR], 6-15), and the median time between the procedure and SCT was 7 weeks (IQR, 5-10 weeks). The median follow-up period was 65 months. The median OS was significantly higher for the SCT group (26 months; 95 % confidence interval [CI], 10.8-41.5 months) than for the NoCT group (12 months; 95 % CI, 9.6-14.4 months) (p < 0.001), with hazard ratio (HR) of 0.22 (95 % CI, 0.08-0.66; p = 0.007) after adjustment for other factors. CONCLUSION: Systemic chemotherapy is associated with improved OS for high-grade MAC patients with unresectable peritoneal metastases who are deemed surgical candidates but underwent an unsuccessful CRS/HIPEC attempt. Further prospective studies with a larger sample are required to identify patient subgroups who benefit the most from SCT.

Outcomes for Elderly Ovarian Cancer Patients Treated with Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

BACKGROUND: Women 65 years of age or older with epithelial ovarian cancer (EOC) are thought to have a worse prognosis than younger patients. However, no consensus exists concerning the best treatment for ovarian cancer in this age group. This report presents outcomes for patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A prospective database of EOC patients treated with CRS/HIPEC (1998-2019) was analyzed. Perioperative variables were compared by treatment including upfront CRS/HIPEC, neoadjuvant chemotherapy plus CRS/HIPEC (NACT + CRS/HIPEC), and salvage CRS/HIPEC, and by age at surgery (< 65 and ≥ 65 years). Survival analysis was performed, and outcomes were compared. RESULTS: Of the 148 patients identified, 42 received upfront CRS/HIPEC, 48 received NACT + CRS/HIPEC, and 58 received salvage CRS/HIPEC. Each group was subdivided by age groups (< 65 and ≥ 65 years). The median overall survival (OS) after the upfront CRS/HIPEC was 69.2 months for the patients < 65 years of age versus 69.3 months for those ≥ 65 years of age. The OS after NACT + CRS/HIPEC was 26.9 months for the patients < 65 years of age versus 32.9 months for those ≥ 65 years of age, and the OS after salvage CRS/HIPEC was 45.6 months for the patients < 65 years of age versus 23.9 months for those ≥ 65 years of age. The median progression-free survival (PFS) after upfront CRS/HIPEC was 41.3 months for the patients < 65 years of age versus 45.4 months for those ≥ 65 years of age. The PFS after NACT + CRS/HIPEC was 16.2 months for the patients < 65 years of age versus 11.2 months for those ≥ 65 years of age, and the PFS after salvage CRS/HIPEC was 18.7 months for the patients < 65 years of age versus 10 months for those ≥ 65 years of age. The median follow-up period for the entire cohort was 44.6 months [95% confidence interval (CI) 34.7-60.6 months]. CONCLUSION: Age and feasibility of complete cytoreduction should be considered when treatment methods are selected for elderly patients. A carefully selected elderly population can benefit significantly from aggressive treatment methods.

Surgical and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a nonacademic center: 25-year experience.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is predominantly performed and studied in academic centers. While developing CRS/HIPEC programs in nonacademic hospitals can increase accessibility, its safety and oncological efficacy remains unclear. We evaluated CRS/HIPEC outcomes in a nonacademic setting. METHODS: A single-center descriptive study was conducted using a prospective database. Data of all CRS/HIPEC attempts in peritoneal surface malignancies (PSM) patients from October 1994 to November 2019 were extracted. Surgical and survival outcomes were measured. Center experience was assessed by quartiles of cases. RESULTS: Overall, 856 patients underwent 948 CRS/HIPEC attempts: 788 (83%) completed CRS/HIPECs, 144 (15%) aborted HIPECs, and 16 (2%) complete cytoreductions (CC-0/1) without chemoperfusion. For completed CRS/HIPECs, median peritoneal cancer index was 24 (interquartile range: 10-33) and CC-0/1 rate was 88%. Major complications occurred in 23.5% with 30- and 100-day mortality of 1.0% and 2.3%, respectively. Median overall survival was 68 months (95% confidence interval [CI]: 50-86). Median progression-free survival was 37 months (95%CI: 28-46). Incomplete cytoreduction and major complication rates decreased over time, while mortality remained low and constant. CONCLUSIONS: CRS/HIPEC at a nonacademic center with advanced surgical and auxiliary services is a safe option to treat PSM with favorable surgical and oncological outcomes.

Outcomes in Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is often misclassified and mistreated due to mixed histologic features. In general, cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard of care for peritoneal carcinomatosis (PC) from mucinous appendiceal tumors; however, in PC from GCA, data are limited and the role of CRS/HIPEC is controversial. We report outcomes in PC from appendiceal GCA treated with CRS/HIPEC. PATIENTS AND METHODS: A prospective institutional database of 391 CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2018 was reviewed. Twenty-seven patients with GCA were identified. Perioperative variables were described. Survival was estimated using the Kaplan-Meier method. RESULTS: GCA occurred in 7% (27/391) of appendiceal CRS/HIPEC patients. Seven (26%) cases were aborted. Two patients underwent a second CRS/HIPEC for peritoneal recurrence. Median age at diagnosis was 53 years (range 39-72 years), and 12 (60%) were female. All underwent previous surgery. Seven (35%) had prior chemotherapy and received a median of 5 cycles (range 3-8). Median PCI was 6 (range 1-39). Complete cytoreduction was achieved in 95% (19/20). Grade III complications occurred in three (15%) patients, and no perioperative deaths occurred. Median follow-up was 97 months. Overall survival at 1, 3 and 5 years was 100%, 74% and 67%, respectively. Progression-free survival at 1, 3, and 5 years was 94%, 67% and 59%, respectively. CONCLUSION: CRS/HIPEC should be considered as the main treatment option for patients with PC from appendiceal GCA. When performed at a CRS/HIPEC specialty center, 5-year OS of 67% can be achieved.

Impact of Mucin Cellularity and Distribution on Survival in Newly Diagnosed Patients with Low-Grade Appendiceal Mucinous Neoplasm Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are tumors that frequently present with peritoneal spread of either acellular mucin (AM) or cellular mucin (CM). We aim to determine how mucin types and distribution affect survival. PATIENTS AND METHODS: A retrospective cohort study was conducted using a prospective database. Newly diagnosed LAMN patients with AM versus CM treated with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were compared. Postoperative pathology reports were reviewed to assess each involved abdominal zone. Survival was analyzed using the Kaplan-Meier method. RESULTS: Of 121 identified patients, 50 (41%) had peritoneal lesions with AM and 71 (59%) with CM. Peritoneal cancer index was lower in AM versus CM (mean: 19 ± 13 vs 28 ± 10, p = 0.004), but complete cytoreduction (CC) rates were similar (98% vs 96%, p = 0.642). The 5-year progression-free survival (PFS) was higher in AM versus CM (96% vs 69.8%, p = 0.002). CM patients had zones with both types of lesions: with and without cells. The CM subgroup analysis showed significant differences in 5-year progression-free survival (PFS) among patients with 1-3, 4-7, and 8-10 zones with cells (95.2%, 68.4%, and 35.7%, respectively, p < 0.001), but PFS was not affected by the number of zones with any lesion type. There was no difference in overall survival (OS) between groups. CONCLUSIONS: Despite comparable CC rates after CRS/HIPEC, CM patients have shorter PFS than AM patients. In CM patients, more zones with cells, but not the total number of involved zones, negatively impact PFS. Mucin type does not impact OS. It is important to assess and report mucin cellularity in LAMN specimens.

Defining "Complete Cytoreduction" After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for the Histopathologic Spectrum of Appendiceal Carcinomatosis.

BACKGROUND: The completeness of cytoreduction (CC) score, which quantifies residual tumor, is a major prognostic factor when treating appendiceal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Both CC-0 and CC-1 are considered complete cytoreductions (CC-0/1) and associated with the best outcomes. We analyzed if the CC-0/1 definition is reliable across appendiceal histopathologic subtypes. METHODS: A prospective database of CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2019 was reviewed to identify patients with CC-0/1. Kaplan-Meier overall survival (OS) and progression-free survival (PFS) by CC-score for each histopathology were calculated. RESULTS: Overall, 297 patients had CC-0/1. Mean age was 54 ± 12 years with 67% females. Histopathologic subtypes were 45% low-grade mucinous carcinoma peritonei (LGMCP), 27% high-grade MCP (HGMCP), 20% HGMCP with signet ring cells (HGMCP-S), and 8% goblet cell adenocarcinoma (GCAC). CC-0 and CC-1 occurred in 57% and 43% of LGMCP, 65% and 35% of HGMCP, 68% and 32% of HGMCP-S, and 79% and 21% of GCAC, respectively. OS and PFS were statistically longer for CC-0 versus CC-1 in HGMCP-S (p = 0.001 and p = 0.005, respectively) and GCAC (p < 0.001 and p < 0.001), but not in LGMCP (p = 0.098 and p = 0.398) or HGMCP (p = 0.167 and p = 0.356). CONCLUSIONS: Survival outcomes for CC-0 and CC-1 after CRS/HIPEC are different for HGMCP-S and GCAC but not for LGMCP and HGMCP. In HGCMP-S and GCAC, only CC-0 should be considered a complete cytoreduction and analyzed separately from CC-1. This distinction is key to understand disease behavior, accurately address patient prognosis, and explore new treatment strategies.

Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998-2017 was reviewed. Perioperative variables and survival were analyzed. RESULTS: Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021). CONCLUSIONS: The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.

Selection and Characteristics of Patients with Peritoneal Dissemination from Appendiceal Cancer with Exceptional/Poor Survival After CRS/HIPEC.

BACKGROUND: Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. METHODS: Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. RESULTS: LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). CONCLUSIONS: Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.

External Validation of the Simplified Preoperative Assessment for Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: MD Anderson Cancer Center developed a computed tomography (CT)-based preoperative assessment tool simplified preoperative assessment for appendix tumor (SPAAT) for predicting incomplete cytoreduction (IC) in low-grade mucinous adenocarcinoma (LGMA) of the appendix, based on preoperative CT scans. This study independently evaluates the tool's performance. METHODS: Seventy-six preoperative CT scans of LGMA patients were evaluated by two surgeons unfamiliar with the patients' medical history. Scores were assigned based on SPAAT criteria, with a SPAAT ≥3 predictive of IC. Binary regression analyses and area under the receiver operating characteristic (AUROC) curve analyses were performed. Patients with splenic resection were excluded due to the structure of the SPAAT assessment tool. RESULTS: Seventy-six LGMA patients underwent attempted cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Of 68 patients, 58 had complete cytoreduction and 10 had IC; 8 patients were ineligible due to prior splenectomy. The mean SPAAT score was 0.8, with six patients having SPAAT scores ≥3. SPAAT scores ≥3 were predictive of IC, with a hazard ratio (HR) of 19 (95% confidence interval 2.8-124.1) (p = 0.002). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 40, 97, 50, and 90%, respectively. A SPAAT score ≥3 was not associated with worse survival prognosis. Median follow-up was 2.4 years and AUROC curve was 71%. SPAAT components with respective HR and p-values were foreshortening of the bowel mesentery (29.5; p = 0.004), and scalloping of the pancreas (9; p = 0.008), spleen (4.3; p = 0.04), portal vein (3.1; p = 0.4), and liver (2.1; p = 0.3). CONCLUSION: A SPAAT score ≥3 predicted IC based on a binary regression model. The clinical value of this score is controversial due to low sensitivity and PPV.

The 7th Edition of the AJCC Staging Classification Correlates with Biologic Behavior of Mucinous Appendiceal Tumor with Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

PURPOSE: We evaluated the 7th edition of the American Joint Committee on Cancer (AJCC) staging classification in terms of overall survival (OS) in patients with PMP treated with cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A total of 208 PMP patients treated with CRS/HIPEC were identified from a prospective database. Patients with peritoneal mucinous carcinomatosis (PMCA) were retrospectively staged at time of diagnosis according to AJCC staging classification. Patients with disseminated peritoneal adenomucinosis (DPAM) were evaluated in a separate group. RESULTS: Median follow-up was 5.2 years. Of 208 patients, 124 had PMCA and 84 patients had DPAM. According to the AJCC staging classification 47 lymph node (LN) negative patients with well-differentiated PMCA, were classified as a stage IVA. 77 patients with either moderately or poorly differentiated PMCA irrespective of LN status, or well-differentiated PMCA with positive LN were classified as stage IVB. 84 patients with DPAM, constituted a separate group. OS of stage IVA and IVB patients was 100, 90, 67, and 91, 50, and 27 for 1, 3, and 5 years, respectively (p < 0.001). OS of DPAM patients was 96, 90, and 88 % for 1, 3, and 5 years, respectively (p = 0.025 comparing to IVA). PFS was estimated for IVA and IVB PMCA patients who were considered disease free after CRS/HIPEC and was 78, 52, and 43 % in the IVA patients and 65 %, 15 %, and 0 in the IVB group at 1, 3, and 5 years, respectively (p = 0.004). The adjusted HR for AJCC stages (IVA/IVB) was 3.7 (95 % confidence interval 2.0-6.7) (p < 0.001). CONCLUSIONS: The 7th edition of the AJCC staging classification is a simple, reproducible, and valid classification for staging patients with PMCA undergoing CRS/HIPEC.

Morbidity of the abdominal wall resection and reconstruction after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

BACKGROUND: CRS/HIPEC has evolved as a therapeutic option for selected patients with peritoneal surface malignancies. To achieve complete cytoreduction (CC), some patients require extensive abdominal-wall resection (AWR) and subsequent complex reconstructions, which may be associated with wound complications (WC) and delay of postoperative cancer therapy. METHODS: Review of a prospective database of 350 patients revealed 213 patients with peritoneal carcinomatosis who underwent AWR due to suspected or proven wound/port site metastases during CRS/HIPEC. Tumor origin included: appendix, colon, ovarian, peritoneal mesothelioma, primary peritoneal, and others. WC were related to peritoneal carcinomatosis index (PCI), CC score, length of surgery, type of AWR and closure, blood transfusion, and albumin levels using binary logistic regression (odds ratios (OR) and 95 % CIs) analysis. RESULTS: PCI ≥ 20 was found in 151 (71 %), CC was achieved in 178 (84 %). Mean length of surgery was 613 min. Postoperative WC were detected in 49 of 213 (23 %) patients, 13 (6 %) had Grade III (according to Clavien-Dindo's classification) WC, and led to delay of postoperative chemotherapy. WC occurred in 21 of 64 (32.8 %) patients with excision of port sites (odds ratio [OR] = 2.11, confidence interval [CI] = 1.09-4.10, p = 0.026). Primary fascial closure was performed in 191 of 213 (89.7 %) patients, 40 (21 %) of whom had WC. Mesh-assisted abdominal wall reconstruction was required in 22 of 213 (10.3 %) patients, of whom 9 (40.9 %) had WC (OR = 2.61, CI = 1.04-6.55, p = 0.035). CONCLUSIONS: Port-site excision and mesh-assisted abdominal wall reconstruction were associated with higher incidence of postoperative WC following CRS/HIPEC. The implications of these preliminary findings may need to be considered during surgical planning for these patients.