Repeat Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Appendiceal Adenocarcinoma: A Viable Treatment Strategy with Demonstrable Benefit.

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.

Cancer-specific survival in non-mucinous appendiceal adenocarcinomas after local resection versus right hemicolectomy: A Surveillance, Epidemiology, and End Results database study.

BACKGROUND: Adenocarcinomas of the appendix are rare cancers for which no National Comprehensive Cancer Network guidelines exist, and for patients who undergo resection with curative intent, there is a paucity of data on prognostic factors affecting long-term cancer-specific survival. We aimed to compare the cancer-specific survival outcomes in adult patients with appendiceal non-mucinous adenocarcinoma undergoing either local resection versus right hemicolectomy. METHODS: This was a retrospective study from the National Cancer Institute Surveillance, Epidemiology, and End Results of patients who underwent curative resection over a 15-year period (2004-2019) for primary appendiceal adenocarcinoma. Out of 16,699 patients, 14,945 were excluded (exclusion criteria were non-adenocarcinoma histological types and patients with regional or distant metastasis as per National Cancer Institute Surveillance, Epidemiology, and End Results stage). Effects of factors (age, race, tumor biology [mucinous versus non-mucinous tumors], the extent of resection of the primary lesion, and lymph nodes) on cancer-specific long-term survival were studied. Survival analysis was performed using the Kaplan-Meier method. Survival outcomes were reported as mean survival (months). RESULTS: Of 1,754 patients, 827 (47.1%) were women, and 927 (52.1%) were men. The mean age in years (± standard deviation) was 62.43 ± 14.3. The racial distribution was as follows: Black 237 (13.5%), White 1,398 (79.7%), and Other 119 (6.8%). A total of 771 (44.6%) underwent local resection (appendectomy or segmental resection of colon without lymph node resection), and 983 (55.4%) underwent hemicolectomy with lymph node resection. Favorable survival prognosticators were age <50 years, White race, and well-differentiated histology. Patients with mucinous tumors experienced better survival. Patients who underwent right hemicolectomy with lymph node resection experienced better survival compared with those who had an appendectomy or segmental colonic resection for non-mucinous tumors rather than mucinous tumors. CONCLUSION: We report novel demographic, tumor-related, and operative prognostic factors impacting long-term cancer-specific survival in patients who undergo resection for appendiceal adenocarcinoma. The extent of resection of the primary lesion with draining lymph nodes determines long-term cancer-specific survival in non-mucinous appendiceal adenocarcinomas.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial.

Importance: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. Objective: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. Design, Setting, and Participants: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Interventions: Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. Main Outcomes and Measures: The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). Results: A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. Conclusions and Relevance: In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01946854.

Robotic Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy.

Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS-HIPEC) is traditionally an open operation given the dissection required during cytoreduction. There are reports of minimally invasive HIPECs, but CRS to an accepted completeness of cytoreduction (CCR) has been described less frequently. We report a patient with metastatic low-grade mucinous appendiceal neoplasm (LAMN) to the peritoneum treated with robotic CRS-HIPEC. A 49-year-old male presented to our center following a laparoscopic appendectomy at an outside facility with final pathology showing LAMN. He had a peritoneal cancer index (PCI) score of 5 determined by diagnostic laparoscopy. Given the small amount of peritoneal disease, he was deemed a candidate for robotic CRS-HIPEC. Cytoreduction was completed robotically with a CCR score of 0. He then received HIPEC with mitomycin C. This case shows the feasibility of robotic-assisted CRS-HIPEC for select LAMNs. When appropriately selected, we advocate for the continued use of this minimally invasive approach.

Pathogenesis of histologic variations of appendiceal mucinous neoplasms.

BACKGROUND: In order for peritoneal metastases from a primary appendiceal mucinous neoplasm to occur, the wall of the appendix must perforate to allow mucus with tumor cells access to the peritoneal spaces. With progression the peritoneal metastases show a broad spectrum of tumor biology varying from indolent to aggressive activity. METHODS: The histopathology of peritoneal tumor masses was determined from the clinical material resected at the time of cytoreductive surgery (CRS). All groups of patients were treated by a uniform strategy that involved complete CRS and perioperative intraperitoneal chemotherapy. Overall survival was determined. RESULTS: From a database of 685 patients, four histologic subtypes were identified and long-term survival determined. Four hundred and fifty patients (66.0%) had low-grade appendiceal mucinous neoplasm (LAMN), 37 patients (5.4%) had mucinous appendiceal adenocarcinoma of intermediate subtype (MACA-Int), 159 patients (23.2%) had mucinous appendiceal adenocarcinoma (MACA), and 39 patients (5.4%) had a mucinous appendiceal adenocarcinoma with positive lymph nodes (MACA-LN). The mean survival of the four groups was 24.5, 14.8, 11.2 and 7.4 years, respectively (p < 0.0001). These four subtypes of mucinous appendiceal neoplasms were shown to have distinct survival estimates. CONCLUSIONS: The estimated survival of these four histologic subtypes in patients having a complete CRS plus HIPEC is of value to the oncologist managing these patients. A mutations and perforations hypothesis was offered in an attempt to explain the broad spectrum of mucinous appendiceal neoplasms that exist. Inclusion of MACA-Int and MACA-LN as standalone subtypes was thought to be necessary.

Palliation of mucinous appendiceal neoplasms with peritoneal metastases with total abdominal colectomy.

BACKGROUND: Incomplete cytoreduction for mucinous appendiceal neoplasms is often required to temporarily alleviate symptoms. The surgical technology for this intervention may be complex and result in extensive morbidity and even mortality. Knowledgeable patient selection for this surgery is mandatory. METHODS: A database was used to identify patients who had palliative surgery that included total abdominal colectomy (TAC). Clinical- and treatment-related variables were assessed for their impact on overall survival. RESULTS: Seventy-eight patients had an incomplete cytoreductive surgery (CRS) that included a TAC. The median survival was 2.5 years and the median follow-up was 2 years. Patients with symptoms of abdominal distention and ascites showed a reduced prognosis (p = 0.0254). The low-grade appendiceal mucinous neoplasms (LAMN) and mucinous appendiceal adenocarcinoma intermediate type (MACA-Int) grouped together showed a prolonged survival (p = 0.0003). MACA with positive lymph nodes showed a reduced survival (p = 0.0009) when compared to MACA patients without positive lymph nodes. A peritoneal cancer index of 1-30 versus >30 and completeness of cytoreduction score of 2 versus 3 were not significant. CONCLUSION: TAC with end ileostomy was used as a treatment option to provide palliation of patients having an incomplete CRS for appendiceal mucinous neoplasms. With LAMN or MACA-Int, median survival was 5.0 years. The surgery can be performed with a morbidity of 9.0% and mortality of 2.6%. Although not considered a palliative option in the past, these data suggest TAC may be used with acceptable results in this group of patients.

Total abdominal colectomy to facilitate complete cytoreduction in 56 patients with mucinous appendiceal neoplasms with peritoneal metastases.

BACKGROUND: Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy are currently the standard of care for management of appendiceal mucinous neoplasms with peritoneal metastases. The goal of the CRS is complete removal of all visible disease through the use of peritonectomy procedures and visceral resections. One of the major resections that may be required is total abdominal colectomy (TAC). METHODS: From a database and secured files of patients having a complete CRS, all patients who had TAC were identified. The clinical and histologic variables associated with these patients were identified and assessed for their impact on overall survival. RESULTS: The 450 complete CRS with low-grade appendiceal mucinous neoplasms had 26 TAC (5.8%) with a 16.0-year median survival. The mucinous adenocarcinoma (MACA)-Intermediate (MACA-Int) group consisted of 37 patients with 8 patients (21.6%) having TAC that resulted in a median survival of 11.5 years. The 159 complete CRS with MACA had 22 TAC (13.8%) with a median survival of 7.5 years. There was a single mortality with a class 4 adverse event in 5 patients (10.7%). With a class 4 adverse event, survival decreased significantly (p = 0.0006, hazard ratio: 6.2). CONCLUSION: Complete CRS required TAC in 56 of 646 patients (8.7%) with appendiceal mucinous neoplasms. With TAC, median survival was 12.0 years. A class 4 adverse event markedly reduced survival.

Secondary cytoreductive surgery for 86 patients with mucinous appendiceal adenocarcinoma.

BACKGROUND: After patients have a surgical procedure for a gastrointestinal cancer, follow-up is indicated. If cancer progression is documented in patients with mucinous appendiceal adenocarcinoma (MACA), a secondary cytoreductive surgery (SCRS) may be considered. METHODS: In patients who had a prior complete cytoreductive surgery (CRS), variables associated with the index CRS and SCRS were extracted. These variables were statistically assessed for their impact on survival. RESULTS: Of 198 MACA patients, 86 (43.4%) had SCRS. The median follow-up was 5.0 years and the median survival was 7 years. Significant prognostic variables associated with the index CRS by univariant analysis was histopathologic grade of MACA-Intermediate (MACA-Int) as compared to other MACA histologic subtypes (p = 0.0164). Significant prognostic variables associated with the SCRS were bowel obstruction (p = 0.0149), interval of CRS to SCRS (p = 0.0059), and completeness of cytoreduction (p = 0.0014). CONCLUSIONS: In the analysis of variables from SCRS, the interval from CRS to SCRS ≤24 months indicates an aggressive biology of the disease. The CC score of complete versus incomplete decreased median survival from 11 to 4 years. A composite of these two variables allowed prediction of survival of 50% when patients showed these two favorable variables and only 9.1% when these variables were unfavorable.

Comparing Survival Outcomes and Impact of EPIC in Patients Undergoing CRS/HIPEC for Mucinous Appendiceal Neoplasm.

BACKGROUND/AIM: This study sought to investigate the difference in survival outcomes in patients with complete cytoreduction (CC)-0 or CC-1 mucinous appendiceal cancer undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). It also investigated what effect early postoperative intraperitoneal chemotherapy (EPIC) may have on survival based on CC score and histology. PATIENTS AND METHODS: This was a retrospective single centre study of patients that underwent CRS/HIPEC +/- EPIC for mucinous appendiceal neoplasms from June 2003 to February 2022. RESULTS: A total of 545 patients were identified. Although there was a survival difference between CC-0 and CC-1 on univariate analyses, this was not statistically significant on multivariate analysis. Histology, peritoneal cancer index, and EPIC status were demonstrated to be independent factors that affected overall survival (OS) on multivariate analysis. Patients with CC-1 that received EPIC had significantly improved OS (mean OS 14 years) when compared to patients that did not receive EPIC (mean OS 6 years). In CC-1, OS was significantly improved in patients that received EPIC in both low-grade (p<0.001) and high-grade (p=0.012) disease. OS for patients that received EPIC at 1, 5, and 10 years was 95%, 80%, and 59%, respectively. OS for patients that did not receive EPIC at 1, 5, and 10 years was 84%, 49%, and 30%, respectively. CONCLUSION: There was no difference in OS between CC-0 and CC-1. The implementation of EPIC in patients with CC-1 significantly improved OS in both low-grade and high-grade disease and thus we recommend its addition in CC-1 disease to achieve optimal survival outcome.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

BACKGROUND: Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. METHODS: Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. RESULTS: The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). CONCLUSION: The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. MATERIALS AND METHODS: A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. RESULTS: We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. CONCLUSIONS: In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

Incomplete cytoreduction with peritoneal metastases from appendiceal mucinous neoplasms.

BACKGROUND: Complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy is the standard of care for mucinous appendiceal neoplasms with peritoneal metastases. Despite many publications regarding selection factors favoring a complete CRS, incomplete CRS does occur. Patients with an incomplete CRS are the focus of this manuscript. METHODS: A retrospective analysis of prospective, histologic, and perioperative data was performed. Overall survival was the endpoint for the numerous assessments. Judgments regarding when to and when not to proceed with an incomplete CRS were sought. RESULTS: From a database of 949 patients who underwent an index CRS for appendiceal mucinous neoplasm, 264 patients (27.8%) had an incomplete CRS. The median overall survival was 1.8 years. Low-grade histopathology and absence of tense ascites or bowel obstruction were significantly associated with increased overall survival. More extensive surgery suggested a more favorable outcome. CONCLUSIONS: When a surgeon is confronted by a procedure that will inevitably end with an incomplete CRS, a current trend is to close quickly and always avoid complications. Patients with low-grade neoplasms who present in the absence of tense ascites or bowel obstruction may gain years of survival by surgical reduction of tumor burden.

Secondary cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: In patients with low-grade appendiceal mucinous neoplasms (LAMN), a secondary cytoreductive surgery (SCRS) is often performed if recurrent disease is detected. METHODS: In patients with a complete cytoreductive surgery (CRS), the clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on overall survival after SCRS. RESULTS: Eighty-eight patients of 450 patients (19.6%) had SCRS. The mean survival was 15.3 years for patients requiring SCRS as compared to 24.5 years for the group as a whole. Variables associated with improved survival as a result of the index CRS by multivariant modeling were absence of total gastrectomy (p = 0.0038), moderate peritoneal cancer index of 15-30 (p = 0.0020) and time interval of greater than 36 months from CRS to SCRS (p = 0.0013). Multivariant modeling associated with SCRS were complete CRS (p = 0.0104) and disease progression limited to the abdominal wall (p = 0.0106). Early postoperative intraperitoneal chemotherapy (EPIC) 5-fluorouracil used with CRS improved the outcome with SCRS (p = 0.0095). CONCLUSIONS: A requirement for SCRS in 88 patients decreased median survival to 15.3 years as compared to 24.5 years in all 450 LAMN patients (p < 0.0001). Prognostic indicators from both the index CRS and the SCRS had an impact on the outcome of SCRS.

Lymph node positive pseudomyxoma peritonei.

BACKGROUND: Appendiceal mucinous neoplasms are routinely accompanied by peritoneal metastases at the time of diagnosis of the primary appendiceal tumor. In contrast, liver metastases and lymph node metastases are unusual. METHODS: From an extensive database, patients with lymph node metastases identified at the time of primary appendiceal cancer resection were selected for special study. The clinical, treatment-related and histologic variables of this group of patients were statistically analyzed for their impact on overall survival. RESULTS: From a prospectively maintained database of 685 patients with a complete cytoreduction of a mucinous appendiceal neoplasm with peritoneal dissemination, 39 patients (5.6%) had lymph node metastases at the time of primary diagnosis. The median follow-up was 5.0 years and overall median survival was 6.0 years. Histologically, 6 of these patients (15.4%) had an appendiceal mucinous neoplasm - Intermediate type (MACA-Int). In 5 patients, the involved lymph nodes were not within the ileocolic lymph node group. The 7 patients (17.9%) who had a complete or near complete response to neoadjuvant chemotherapy prior to definite cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) showed prolonged survival (HR 4.8 (1.1, 20.5) p = 0.0323). A prior right colon resection required repeat resection in 87% of patients. CONCLUSION: Long-term survival is unusual but occasionally seen in this group of patients. Response to neoadjuvant chemotherapy is an important determinant of a favorable outcome.

Mucinous adenocarcinoma of the prostatic urethra after brachytherapy for prostatic adenocarcinoma: a case series.

Mucinous adenocarcinoma of the urethra is extremely rare, even more so in a setting of postradiation therapy, with only 3 cases reported up to date including the first case published by our group in 2011. In the present study, we included the long-term follow-up on our previously reported case and report 3 additional cases. This is the first case series to date of this rare disease entity. The aim of this study is to review the clinicopathologic features of mucinous adenocarcinoma of the prostatic urethra in patients after receiving brachytherapy for prostatic adenocarcinoma. We identified 4 patients with a mean age of 72 years, and a mean interval of 14.8 years from brachytherapy for prostate carcinoma (grade group 1). Patients presented with hematuria or urinary retention. A colonoscopy was performed in three-fourth of patients and was within normal limits. Three patients underwent cystoprostatectomy and 1 had a transurethral resection of the prostate. On gross examination, only tumor formed a 3.5 cm tan-gray, ulcerated, friable, and necrotic mass and 2 displayed either irregular red granular or thickened areas within the prostatic urethra. Abundant extracellular mucin pools dissecting the prostatic stroma were present in all tumors, with clusters of tumor cells floating in the mucin. The mucin pools were lined by pleomorphic pseudostratified columnar mucinous epithelium. Tumors were diffusely positive for CK20, CDX2 (4/4), and AMACR (2/2); they focally expressed CK7 (2/4), and lacked nuclear ß-catenin expression (3/3). PSA, PSAP, NKX3.1, p63, and GATA3 were negative in the tumors tested. Among the 3 patients who underwent radical surgery, 2 had stage 2 tumors (confined to the prostatic urethra and prostate), and 1 had a stage 3 tumor, with seminal vesicle involvement. All 4 patients were alive without disease with a mean follow-up of 4.9 years. In conclusion, brachytherapy-associated mucinous adenocarcinoma of the prostatic urethra displays intestinal-type features as its non-radiation-related counterpart. It appears to lack a villous adenoma component, displays a different immunohistochemical profile with diffuse CK20 and CDX2 positivity, and is associated with lower stage and less aggressive behavior.

Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC.

BACKGROUND: Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS: Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS: The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS: An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

A proposal for changing nomenclature from pseudomyxoma peritonei (PMP) to abdomino-peritoneal mucinous carcinoma (APM) based on its long journey and experience from tertiary oncology center in India.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a generalized term, usually known as "jelly belly" since 1884. Incidence is very low, 1-3 per million people per year. Because of its indolent nature, it is usually diagnosed at an advanced stage, thereby impacting the quality of life. The 5-year survival rate varies from 23 to 86% in world literature. Even 10 years and 20 years of survival have been described. With our experience, we like to propose rename of PMP as abdomino-peritoneal mucinous carcinoma (APM) as we strongly feel the time has come to specify the term and standardize the management strategy. METHODOLOGY: In the premier institute of India and as a tertiary referral center, we experienced the maximum number of advanced cases of APM. From 2012 to 2021, we analyzed all the APM patients based on a prospectively maintained computerized database in the department of surgical oncology and found the reasons for renaming from this traditional one. RESULTS: We included a total of 87 patients who underwent surgical intervention. Thirty-five patients underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and 52 patients underwent debulking. In CRS-HIPEC patients, CC-0 was achieved in 28 patients (80%), CC-1 in 4 patients (11.4%), and CC-2 in 3 patients (8.6%). Palliative intent HIPEC was done in 3 patients (8.6%). Clavien-Dindo grade III and IV morbidity was observed in 18.8% of patients with 90 days mortality of 5.7%. CONCLUSION: With our long-term experience and advancement of scientific evidence, we like to propose a new name for PMP as APM. We strongly believe this paper will give a clear picture of this rare disease and standard management outlines.

Prognostic prediction of preoperative nutritional status in low-grade appendiceal mucinous neoplasms.

To describe the preoperative nutritional status of Low-grade Appendiceal Mucinous Neoplasms (LAMNs) and identify prognostic factors for survival. Medical records from 165 patients with LAMNs who attended the Aerospace Center Hospital, Beijing, China between January 2017, and December 2018 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model. Among 165 patients, 59 (36%) were male and 106 (64%) were female. Patient's median age was 58 years (range 20 to 78 years). Univariate analysis indicated that gender, weight loss, prior surgical score (PSS), red blood cell, albumin, peritoneal cancer index (PCI), completeness of cytoreduction (CCR), and hyperthermic intraperitoneal chemotherapy (HIPEC) were related to prognosis. Multivariate analysis showed that PSS, CCR and HIPEC were independent predictors of prognosis. The preoperative nutritional status of patients plays an important role in predicting prognosis. Patients can benefit from a complete cytoreductive surgery (CCRS) and HIPEC in an experienced institution for the first medical treatment.