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.

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.

Predicting Aborted Hyperthermic Intraperitoneal Chemotherapy (AHIPEC) with Preoperative Tumor and Inflammatory Markers in Potentially Resectable Appendiceal Cancer Patients with Peritoneal Carcinomatosis.

BACKGROUND: Despite meticulous preoperative diagnostics, aborted hyperthermic intraperitoneal chemotherapy (AHIPEC) is a common, unsuccessful outcome of curative cytoreductive surgery (CRS)/HIPEC. OBJECTIVE: The aim of this study was to evaluate the association between AHIPEC and preoperative risk factors of patients with mucinous appendiceal cancer (AC). METHODS: A single-institute, case-control study was conducted using a prospective database. Potentially resectable patients with peritoneal carcinomatosis of mucinous AC origin with AHIPEC between October 1994 and February 2019 were identified. Preoperative risk factors were reviewed. Analysis was conducted by tumor grade: low-grade, high-grade, and signet ring cell carcinoma (high-S). All available tumor-type-matched successful CRS/HIPEC controls were obtained from the same database. Univariable and multivariable analyses were performed. RESULTS: Overall, 21, 44, and 15 AHIPEC cases and 153, 133, and 53 tumor-matched controls were identified for low-grade, high-grade, and high-S populations, respectively. Multivariable analysis revealed preoperative cancer antigen (CA) 19-9 > 1 upper limit of normal (ULN) [odds ratio (OR) 6.32; p = 0.014], CA125 > 2 ULN (OR 7.02; p = 0.039), C-reactive protein (CRP) > 2.5 mg/L (OR 13.7; p = 0.001), and previous HIPEC (OR 7.5; p = 0.031) were significantly associated with AHIPEC in the low-grade population. Preoperative CRP > 2.5 mg/L (OR 7.77; p < 0.0001) and previous HIPEC (OR 4.69; p = 0.004) were associated with AHIPEC in a multivariable model for high-grade AC. No single factor showed a significant association with AHIPEC in high-S patients. CONCLUSION: Risk factors vary for AHIPEC among low-grade, high-grade, and high-S AC histology. Elevated preoperative CA19-9, CA125, CRP, and previous HIPEC should be considered in the selection process for CRS/HIPEC in low-grade AC, as well as elevated CRP and previous HIPEC in high-grade AC, to avoid unnecessary surgery.

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.

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.

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.

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.

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.

Efficacy of Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Treatment of Recurrent Uterine Sarcoma.

OBJECTIVE: Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. METHODS/MATERIALS: A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. RESULTS: A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III-IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. CONCLUSIONS: Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.

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.

Port-site metastases is an independent prognostic factor in patients with peritoneal carcinomatosis.

INTRODUCTION: Port-site metastases (PSMs) have been reported after laparoscopy in patients with peritoneal carcinomatosis (PC). We hypothesize that PSM is an independent negative predicting factor of survival in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A retrospective review of a prospective database was conducted to search patients who underwent laparoscopy prior to CRS/HIPEC. Most of the tumors were of appendiceal origin. All previous laparoscopy port sites were excised regardless of macroscopic tumor involvement. Patients were divided into two groups: patients with PSM [PSM (+)] and patients without PSM [PSM (-)]. Overall survival (OS) was estimated by Kaplan-Meier curves and the log-rank test. Cox regression [hazard ratios (HRs) and 95 % confidence intervals (CIs)] was used to test for independent effects of the PSM (+) and the associated clinicopathological variables. RESULTS: Sixty-five patients had laparoscopy before CRS/HIPEC. One hundred and forty-four port-sites were resected; 41 (29 %) ports were positive for malignancy in a total of 22 (34 %) patients. Mean OS at 1, 3, and 5 years was 88, 66, and 63 %, respectively. Survival in patients with PSM was 73, 35, and 23 %, respectively, compared with 95, 82, and 82 %, respectively, in patients without PSM (p ≤ 0.001). Positive lymph nodes (LNs) were detected in 13/22 patients with PSM and 11/43 patients without PSM. Independent effects on survival shows an HR of 3.136, 95 % CI 1.150-8.549 (p = 0.026) for LN metastases, and an HR of 3.462, 95 % CI 1.198-10.006 (p = 0.022) in patients with positive PSM. CONCLUSION: PSMs are common in patients with PC undergoing CRS/HIPEC and are independently associated with a worse prognosis. Resection of previous laparoscopy port sites is advocated in patients with PC to ensure complete cytoreduction.

Melphalan: a promising agent in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for peritoneal carcinomatosis (PC). Frequently, these patients have failed systemic chemotherapies and surgeries, including CRS/HIPEC with traditional regimens (mitomycin-C or platinum based). An alternative agent for failed or repeated CRS/HIPEC is unknown. We hypothesize that melphalan is an alternative agent in patients with PC from aggressive primaries, including recurrences following failed regional therapies. METHODS: A retrospective review of a prospective database of 247 patients revealed 25 patients (9 male and 16 female) who received intraperitoneal melphalan (50 mg/m(2)) in 31 CRS/HIPEC procedures, of which 19 were repeated. Primary malignancies included 17 appendiceal, one colorectal, two ovarian, two uterine sarcomas, two primary peritoneal and one mesentery sarcoma. RESULTS: PC index (PCI) was ≥20 in 76 % of patients (19/25). 88 % of patients (22/25) had complete cytoreduction. Seventeen patients were alive, with mean survival of 63.6 months, and eight patients are deceased. Overall survival (OS) for the entire group since diagnosis was 95.8, 84.5, 50.9, and 38.2 % at 1, 3, 5, and 10 years, respectively; OS since melphalan HIPEC was 89.4, 45, and 30 % at 1, 3, and 5 years, respectively; and OS in patients with appendiceal malignancies was 91.7, 48.1 and 32.1 % at 1, 3 and 5 years, respectively. There was no postoperative mortality. Grade III-IV morbidity was 23 % (7/31). Nine patents had neutropenia, controlled with filgrastim. CONCLUSIONS: Melphalan is an efficacious alternative agent in patients undergoing CRS/HIPEC for aggressive and recurrent peritoneal surface malignancies. Its postoperative significant myelosuppression effect should be addressed.

Predictive and prognostic survival factors in peritoneal carcinomatosis from appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefit in the treatment of selected patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We evaluated factors affecting the survival of patients with PC from AC after CRS/HIPEC. METHODS: A retrospective analysis of 387 CRS/HIPEC procedures performed between February 1998 and February 2013 identified 202 patients with PC from AC. Tumor histopathology, complete cytoreduction (CC 0-1), Peritoneal Cancer Index (PCI), and lymph node (LN) status were related to overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. RESULTS: Overall, 129 women (64 %) and 73 men (36 %), mean age 54 years (range 25-81), with a mean follow-up of 36 months were included in the study. Seventy-seven low-grade tumors (disseminated peritoneal adenomucinosis [DPAM]; 38 %) and 125 high-grade tumors (peritoneal mucinous carcinomatosis [PMCA]; 62 %) were identified. Five- and 10-year OS was 56 % and 47 %, respectively, with PFS of 44 % at 5 and 10 years. Five-year OS in DPAM patients was 83 %, with a 5-year OS significant difference related to CC 0-1 versus CC 2-3 (incomplete cytoreduction) [p = 0.021]. Five-year OS in PMCA patients was 41 %, with a 5-year OS significant difference related to CC 0-1 versus CC 2-3 (p < 0.001), PCI <20 versus PCI ≥20 (p = 0.002), and (-)LN versus (+)LN (p < 0.001). Grade III/IV complications were 16 %. No perioperative mortality was reported. CONCLUSION: Positive LN, PMCA histopathology, and PCI ≥20 are negative prognostic factors, while CC 0-1 is a positive survival predictor in PC from AC treated with CRS/HIPEC. However, in patients with PMCA and PCI ≥20 in whom CC 0-1 was a potential outcome should not be denied CRS/HIPEC.