The risk of developing pseudomyxoma peritonei from a non-perforated low grade appendiceal mucinous neoplasm found at appendicectomy.

INTRODUCTION: Low-grade appendiceal mucinous neoplasms (LAMNs) are classified as non-perforated (pTis, pT3) or perforated (pT4), and considered precursors of pseudomyxoma peritonei (PMP). This study aims to quantify the risk of developing PMP from pTis and pT3 LAMNs. MATERIALS AND METHODS: Retrospective analysis of a prospectively collected database identified LAMN patients referred to a specialist centre from 2004 to 2019. pT4 LAMNs and other appendix tumours were excluded. All patients had specialist review of their pathology, operation note, and a CT scan (at least 6 weeks post-operatively). Surveillance CTs were then performed at 6, 12, 24, 36, 48, & 60 months, with tumour markers (CEA, CA19-9, CA125). RESULTS: 193 pT3/pTis LAMN patients were included (pTis = 153, pT3 = 40). Median follow-up = 6.45 (3.91-22.13) years, M:F ratio = 1:1.57, and median age = 57 (23-83) years. Initial surgery included: appendicectomy (67 %), appendicectomy + visceral resection (6 %), and right hemicolectomy (27 %). R1 resections were identified in 5/193 patients (2.5 %). 3 R1 patients underwent re-operation (2 caecal pole excision and 1 ileocecectomy), none of which had residual tumour. 8/193 patients (4 %) were lost to follow up. None of the remaining 185 developed PMP. CONCLUSION: This is the largest reported series of pTis/pT3 LAMNs with standardised follow-up in the literature. LAMNs correctly classified as pT3/pTis (after careful specialist review of pathology, operation note, and a baseline post-operative CT) have negligible risk of developing PMP and should have low intensity surveillance. If completely excised, further surgery is not indicated. R1 resections should be considered on an individual basis at a specialist centre.

Two-stage cytoreductive surgery for 'extensive' pseudomyxoma peritonei: A legitimate alternative or salvage strategy?

BACKGROUND AND AIM: Two-stage cytoreductive surgery (CRS) has been proposed as an alternative to one-stage surgery in patients who have 'extensive' pseudomyxoma peritonei (PMP) and/or are unfit for very extensive surgery, to reduce morbidity. We review current evidence on two-stage CRS focusing on patient selection, interval between procedures, extent of surgery, use of HIPEC, perioperative and oncological outcomes. METHODS: This is a narrative review. A literature search on PubMed and Embase was performed using keywords- 'Two-stage cytoreductive surgery', 'pseudomyxoma peritonei', 'high-volume PMP', 'huge PMP', 'cytoreductive surgery', 'HIPEC', 'staged surgery' and 'extensive pseudomyxoma peritonei'. RESULTS: Five studies reported outcomes in a total of 114 patients. The indications for two-stage CRS were: in two studies, patients undergoing an incomplete cytoreduction due to undue surgical risk were reevaluated for a second surgery during routine surveillance; severe comorbidities in one; extensive disease with PCI>28 in another and in one, only HIPEC was performed as a second procedure due to intraoperative hemodynamic instability (the two-stage procedure was performed in interest of patient's safety). Major morbidity ranged from 0 to 37.5 % (first-stage) and 25%-38.9 % (second-stage). Short term follow-up demonstrated equivalent short-term oncological outcomes compared to historical data. Long term follow-up and quality-of-life data were not available. CONCLUSIONS: The published studies showed different interpretations and applications of the two-stage CRS concept. The reported morbidity was similar to that after single-stage CRS for extensive PMP. Though short-term survival outcomes are acceptable, long-term follow-up is needed. Planned two-stage CRS should currently be reserved for highly selected clinical situations.

Association between preoperative appendiceal histology grade and Pseudomyxoma peritonei grade offers a solution to avoid right hemicolectomy during cytoreductive surgery and HIPEC.

INTRODUCTION & OBJECTIVES: Treatment of PMP consists of appendectomy, cytoreductive surgery (CRS) and HIPEC. Right-sided hemicolectomy is necessary only when PMP is high grade, given the lymphatic invasion risk. To date, no single preoperative factor was identified as predictive of PMP grade. MATERIALS & METHODS: Preoperative factors of a prospective cohort study on PMP were retrospectively analyzed, in order to identify situations linked with high or low grade appendiceal PMP. The main outcome was PMP grade on definitive histology after CRS. RESULTS: n = 105. In univariate analysis, the grade of the appendiceal tumor, systematically reviewed in an expert center, showed an OR of 25.00 (95 % CI: 3.30-189.27; p = 0.001) and an NPV of 93.75 [85.36, 100]. Peritoneal biopsy demonstrated an OR of 19.80 (95 % CI: 2.30-170.71; p = 0.002) and a PPV of 90 [71.41, 100]. In multivariate analysis, these two factors remained significantly associated with PMP grade. CONCLUSION: Whenever appendiceal tumor is low grade on preoperative histology, the colon has to be spared unless completeness of CRS is compromised, which is a high-grade feature in fact. In case of high grade appendiceal tumor and/or peritoneal biopsy, right-sided hemicolectomy is warranted. If no histology is available preoperatively, adapt to intraoperative lesions as no preoperative factors seem to be predictive.

Pseudomyxoma peritonei peritonitis.

Pseudomyxoma peritonei (PMP) is a rare neoplastic condition characterised by gelatinous ascites, which generally arise from mucin-producing appendiceal tumours. Presentation is variable but requires prompt recognition to ensure appropriate specialist management due to risk of malignancy.A male in his 40s presented with a 1-day history of sudden onset, non-migratory abdominal pain, worse in the right iliac fossa. He had no significant medical history nor known drug allergies. Examination revealed right iliac fossa peritonism and blood tests revealed raised inflammatory markers. CT scan showed a right-sided abdominal collection. Intraoperatively, a diagnostic laparoscopy was performed, which revealed extensive mucin in the abdominal cavity. This was washed out and a laparoscopic appendectomy was performed; histopathology confirmed PMP from the ruptured appendix.

[A Case of Perforated Low-Grade Appendiceal Mucinous Neoplasm Diagnosed During Appendectomy].

A 46-year-old female presented persistent right lower abdominal pain for 4 days. Computed tomography revealed an enlarged appendix with a surrounding low-attenuation mass. The patient was diagnosed with appendiceal abscess-forming appendicitis and initially treated with antibiotics. However, owing to the manifestation of nausea as a side effect, laparoscopic appendectomy was performed 3 days after the initial consultation. Intraoperative examination revealed mucinous material on the surface of the appendix and within the abdominal cavity, leading to the decision to perform an appendectomy with partial cecum resection and excision of the omentum with mucinous deposits. Pathological examination confirmed the diagnosis of a perforating low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei. The patient was subsequently referred to a specialized center for ongoing management, and at 9 months postoperatively, surveillance is being conducted. Low-grade appendiceal mucinous neoplasms can progress to pseudomyxoma peritonei through perforation; however, an optimal treatment approach has not yet been established. In particular, patients in advanced stages of the disease often require challenging management decisions. This case is reported along with a review of the literature to provide further guidance.

Mucocoele of the appendix.

Introduction: Mucocoele of the appendix occurs in 0.2-0.7% of people in the world without any well-defined clinical symptoms. It occurs when there is an accumulation of mucous in the lumen of the appendix. Case Presentation: We present three cases: a 48-year-old male admitted to the emergency room with a one-day history of right iliac fossa pain. Abdominal examination was suggestive of acute appendicitis. The initial abdominal computerised tomography scan was reported as being unremarkable. At surgery, a firm tumour of the appendix was found, and a limited right hemicolectomy was done. Histopathology confirmed a mucocoele of the appendix with borderline mucinous histology.The second case is a 63-year-old man who presented with a one-year history of abdominal distension and weight loss. Previous abdominal ultrasound was suggestive of liver cirrhosis with significant ascitic fluid. Abdominal magnetic resonance imaging found an appendix mucocoele with infiltration of the omentum and scalloping of the liver surface suggestive of pseudomyxoma peritonei. A percutaneous biopsy of the omental mass confirmed metastatic mucinous adenocarcinoma of the appendix.The third case is a 68-year-old man who, during an annual medical check-up, had an incidental finding of a cystic right iliac fossa mass on ultrasound, confirmed on abdominopelvic computerised tomography scan to be an appendix mucocele. He had laparoscopic appendicectomy. The histopathological diagnosis confirmed a mucinous cystadenoma of the appendix. Conclusion: Preoperative diagnosis of appendiceal mucocoele is difficult and commonly discovered intraoperatively. The prognosis is good for the histologically benign type, but it is poor when malignant or peritoneal lesions are present. Funding: None declared.

Low-grade appendiceal mucinous neoplasms: Histomorphological spectrum in a tertiary care hospital.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMNs) are benign non-invasive epithelial proliferations of the appendix. These usually present clinically as mucoceles and these rarely exceed 2 cm in diameter. Lesions confined to the lumen are labelled as LAMN; however those in which mucin spreads outside the peritoneum are labeled as pseudomyxoma peritonei (PMP). AIMS AND OBJECTIVE: A retrospective study was conducted over a period of three years and all cases of appendectomies were studied. Twelve cases of LAMN were identified, which is a diagnostic dilemma for the pathologists and clinicians. RESULTS: LAMN was identified based on the histopathological features. Out of the 12 cases, 9 were classified as LAMN and 3 as appendiceal neoplasm with PMP. There was villous or flat proliferation of epithelial lining, loss lymphoid aggregates, and dissecting mucin within muscularis. CONCLUSION: LAMNs are rare neoplasms of the appendix, with clinical presentation similar to acute appendicitis. Mucinous collections within the appendiceal wall should be extensively searched for mucosal changes and, if found, should prompt a careful search for pushing invasion of LAMNs. A thorough and vigilant gross examination can be of great help. Appendicectomy is the treatment of benign and grossly intact mucinous neoplasm.

Pseudomyxoma peritonei leading to "jelly belly" abdomen: a case report and review of the literature.

BACKGROUND: Pseudomyxoma peritonei is an infrequent condition with a global annual incidence of only one to two cases per million people. Mucinous neoplasms, widespread intraperitoneal implants, and mucinous ascites characterize it. Currently, most clinicians misdiagnose this condition, which leads to delayed management. CASE PRESENTATION: A 44-year-old North Indian female presented with a 1.5-month history of an abdominal lump. Physical examination revealed a sizeable abdominopelvic mass at 36 weeks. Contrast-enhanced computed tomography showed a massive multiloculated right ovarian cystic mass measuring 28 × 23 × 13 cm with mild ascites and elevated carcinoembryonic antigen levels (113.75 ng/ml). A provisional diagnosis of ovarian mucinous neoplasm was made, for which the patient underwent laparotomy. Intraoperatively, there were gross mucinous ascites, along with a large, circumscribed, ruptured right ovarian tumor filled with gelatinous material. The appendicular lump was also filled with mucinous material along with the omentum, ascending colon, right lateral aspect of the rectum, splenic surface, and small bowel mesentery. Cytoreductive surgery was performed along with an oncosurgeon, including total abdominal hysterectomy with bilateral salpingoophorectomy, omentectomy, right hemicolectomy, lower anterior resection, ileo-transverse stapled anastomosis with proximal ileal loop diversion stoma, excision of multiple peritoneal gelatinous implants, and peritoneal lavage. Histopathology and immunohistochemistry confirmed the presence of intestinal-type mucinous carcinoma. Postoperatively, the patient was given six cycles of chemotherapy. She tolerated it without any specific morbidity and had an uneventful recovery. Postoperative follow-up at 15 months revealed normal tumor marker levels and abdominal computed tomography findings and no signs suggestive of local recurrence or distal metastases. CONCLUSIONS: Pseudomyxoma peritonei is a rare disease that is frequently misdiagnosed in the preoperative phase. Therefore, radiologists and clinicians should maintain a high index of suspicion for accurate diagnosis and multidisciplinary management.

Omental metastases in patients with pseudomyxoma peritonei or colorectal peritoneal metastases - is routine omentectomy justified?

BACKGROUND: The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM). METHOD: All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses. RESULTS: In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses. CONCLUSION: OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.

Closure of a Gastropleural Fistula Using Advanced Endoscopy.

Gastropleural fistulas are rare complications with significant mortality and morbidity. There are limited reports on the successful management of gastropleural fistulas with advanced endoscopic procedures. The following case of a 75-year-old woman with a history of recurrent pseudomyxoma peritonei secondary to ruptured low-grade appendiceal mucinous neoplasm status post cytoreductive surgery highlights the successful treatment of a gastropleural fistula with endoscopic suturing.

Feasibility of Robot-Assisted Cytoreductive Surgery With Upper-Abdominal Peritonectomy for Pseudomyxoma Peritonei With Low Peritoneal Carcinomatosis Index: A Pilot Study.

INTRODUCTION: Our study's objective was to provide the method for, and preliminary findings from, robot-assisted cytoreductive surgery (r-CRS) combined with upper-abdominal peritonectomy in pseudomyxoma peritonei (PMP) with limited peritoneal surface malignancy (PSM). MATERIALS AND METHODS: We conducted a retrospective pilot study on consecutive patients with PSM secondary to pseudomyxoma peritonei with a peritoneal cancer index (PCI) of under 10 who were indicated for r-CRS combined with upper-abdominal peritectomy. Perioperative and 30-day major morbidity and mortality characteristics were analyzed and compared with cases in which laparoscopic CRS (l-CRS) was performed under the same conditions. RESULTS: Six patients underwent r-CRS combined with an upper-abdominal partial peritonectomy. Their mean PCI was 4.83. Complete cytoreduction was achieved in all patients. The mean duration of the operation was 156.8 minutes. There was no major complication and no mortality. The mean length of hospital stay after surgery was 6.33 days. r-CRS resulted in less blood loss, a lower C-reactive protein level, and a shorter length of hospital stay that were significantly different compared with those of l-CRS. CONCLUSIONS: This is the initial technical report of a robotic approach for CRS combined with upper-abdominal peritonectomy. r-CRS with a combined upper-abdominal peritonectomy was shown to be safe and feasible for PMP with limited PSM.

Hyperthermic intraperitoneal chemotherapy in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei: a 10-year treatment experience in China.

BACKGROUND: To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP). METHODS: We retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC. RESULTS: The 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression. CONCLUSIONS: HIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.

Long-term survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Waikato, Aotearoa New Zealand: a 12-year experience.

BACKGROUNDS: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for selected cases of peritoneal surface malignancy. In 2008, a CRS/HIPEC service was first established in Aotearoa New Zealand (AoNZ) at Waikato and Braemar Hospitals in the Waikato region. METHODS: This is a retrospective review of a prospectively maintained database of all patients undergoing CRS/HIPEC from 1 January 2008 to 1 November 2020 at Waikato and Braemar Hospitals. We analysed long-term survival and predictors of survival for each tumour type. RESULTS: 240 procedures were performed for 221 patients, including 22 re-do procedures. Cases had a median peritoneal cancer index of 16. Complete cytoreduction (CC0-1) was achieved in 196 cases (81.7%). All complete cytoreduction cases received HIPEC. There were 152 pseudomyxoma peritonei (PMP), 39 colorectal cancers (CRC), 29 appendiceal cancers, eight ovarian cancers, six peritoneal mesotheliomas, and six other cancers. The 5-year overall survival (OS) for PMP with acellular mucin, low-grade mucinous carcinoma peritonei, and high-grade mucinous carcinoma peritonei with or without signet cells were 91.6%, 80.5%, and 72.2%, respectively. 2- and 5-year OS in CRC were 56.7% and 40.4%. The achievement of complete cytoreduction improved the 5-year OS to 87.9% across all PMP and 45.1% in colorectal cancer. Incomplete cytoreduction predicted worse survival in appendiceal PMP. In colorectal cancer, worse survival was predicted in those who had incomplete cytoreduction, liver metastasis, and presentation with obstruction and perforation. CONCLUSION: Favourable long-term outcomes following CRS/HIPEC for peritoneal surface malignancy have been achieved in AoNZ through the Waikato peritonectomy service.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

Bland-Altman agreement analysis between CT predicted and surgical peritoneal cancer index in pseudomyxoma peritonei of appendiceal origin.

Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland-Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland-Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9-12). After the Bland-Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland-Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from - 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland-Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as - 0.287 ± 1.955, with the LoAs from - 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P < 0.001, as for selected CT-PCI and surgical PCI, the coefficient was 0.909, P < 0.001. Although there was a strong correlation for both total and selected CT-PCI with surgical PCI, however, the agreement is still not good in Bland-Altman analysis, which suggested that CT-PCI cannot predict surgical PCI accurately even in professional PMP treatment centers. In brief explanation, CT makes it difficult to distinguish the borderline between tumor tissue and mucus and to detect tumor lesions in the small intestine regions, which caused overestimation or underestimation by CT-PCI. In the future, a multiple linear regression model based on CT-PCI might accurately predict surgical PCI preoperatively.

Low-Grade Pseudomyxoma Peritonei Behaving as a High-Grade Disease: A Case Series and Literature Review.

Patients with low-grade appendiceal mucinous carcinomas (LAMNs) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have a favorable prognosis. However, a subgroup of patients presents a clinically aggressive course with disease progression despite receiving treatment. The purpose of this study is to report the experience of clinically aggressive LAMN patients treated by the same team, and to present a review of the literature. The cases of four patients with clinically aggressive LAMNs were reviewed. Clinical and histopathological characteristics were re-examined. Recurrences and the time of recurrence, as well as the survival time, were recorded. These patients were four men with clinically aggressive LAMNs treated with CRS plus HIPEC. One of them underwent CC-0 surgery, two underwent CC-1 surgery, and one underwent CC-3 surgery. All patients received systemic chemotherapy after surgery. Recurrence was recorded in three of the patients within 4-23 months after the initial treatment. Two of the patients underwent secondary CRS. Three patients died of disease recurrence within 13-23 months, and one is alive with a disease relapse at 49 months after his initial surgery. LAMNs were identified in both the initial specimens and the specimens obtained during reoperation. The prognosis of LAMN patients treated with CRS plus HIPEC is favorable. A small number of patients present a clinically aggressive course that is unresponsive to any treatment. Molecular and genetic studies are required to identify this group of LAMN patients who have an unfavorable prognosis.

Low-grade appendiceal mucinous neoplasm encountered during risk-reducing salpingo-oophorectomy: A case of laparoscopic surgery.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare epithelial malignancy of the appendix. If it perforates the abdominal cavity, it can cause a serious clinical syndrome called pseudomyxoma peritonei. In the present case, we laparoscopically removed a LAMN encountered during risk-reducing salpingo-oophorectomy (RRSO). The patient was a 53-year-old woman who was diagnosed with hereditary breast and ovarian cancer syndrome. RRSO was planned, and magnetic resonance imaging revealed a large cystic tumor in the right lower abdomen. We expected an ovarian cyst; however, it was a primary tumor of the appendix. Partial cecal resection was performed laparoscopically by a surgical oncologist. The pathological diagnosis was LAMN. Gynecologists may encounter this disease incidentally. Mucinous appendiceal neoplasm (MAN) may be encountered during RRSO. If a right lower abdominal mass is found near a normal ovary preoperatively, gynecologists should consider MAN as well as paraovarian cyst.