Peritoneal malignancy in the global COVID-19 pandemic: experience of recovery and restoration in a high-volume centre through NHS and independent sector collaboration.

INTRODUCTION: Treatment of peritoneal malignancy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) requires substantial critical care, theatre and nursing resources. The COVID-19 pandemic caused challenges in providing a high volume, tertiary referral service. METHODS: We reviewed data on referrals and operations performed in a tertiary referral centre in both NHS and independent sector settings. The impact of COVID-19 on activity was assessed using 2019 as a benchmark. RESULTS: New patient referrals were similar, with 891 in 2019 compared with 833 in 2020. Delivery of CRS and HIPEC operations were initially impacted by COVID-19. NHS and independent sector collaboration facilitated recovery, with 284 patients treated in 2020 compared with 280 in 2019. CONCLUSIONS: Close collaboration and structural organisation between the clinical and management teams in the NHS and independent sectors facilitated recovery and restoration of a complex tertiary referral service for peritoneal malignancy during the COVID pandemic.

Outcomes of multicystic peritoneal mesothelioma treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, generally considered a borderline malignancy, best treated by cytoreductive surgery (CRS) to remove macroscopic disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Owing to its rarity, little has been published on clinical presentation, clinical behaviour over time, or an optimal treatment approach. METHODS: A prospectively developed peritoneal malignancy database was interrogated for the years 2001-2018. Details on all patients with MCPM as a definitive diagnosis after CRS and HIPEC were analysed, including previous interventions, mode of presentation, surgical treatment, postoperative outcomes, and late follow-up information from abdominal CT and tumour markers. RESULTS: Some 40 patients with MCPM underwent CRS and HIPEC between 2001 and 2018. Of these, 32 presented with abdominal pain, distension or bloating, six patients presented with recurrence following previous surgery at the referring hospitals, and two had coincidental diagnoses during a surgical procedure. CRS involved peritonectomy in all 40 patients. Bowel resection was required in 18 patients, and seven had a temporary stoma. Thirty-eight patients were considered to have undergone a complete macroscopic tumour removal (completeness of cytoreduction CC0), and two had residual tumour nodules less than 2.5 mm in size, classified as CC1. Median duration of follow-up was 65 (range 48-79) months. There were no deaths during follow-up. The Kaplan-Meier-predicted recurrence-free interval was 115.4 months. CONCLUSION: MCPM is a rare peritoneal neoplasm with a heterogeneous pattern of presentation. CRS and HIPEC is an effective management option for this group of patients, with favourable long-term survival.

Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting.

BACKGROUND: Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. METHODS: Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. RESULTS: A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent. CONCLUSION: The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.

ANTECEDENTES: El mesotelioma peritoneal (peritoneal mesothelioma, PM) es una neoplasia primaria del peritoneo muy poco frecuente, con una incidencia creciente en todo el mundo. La cirugía citorreductora (cytoreductive surgery, CRS) con quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) se ha mostrado prometedora como estrategia de tratamiento. En marzo de 2016, se organizó una reunión por videoconferencia del equipo multidisciplinar nacional de PM (national PM multi-Disciplinary Team, MDT) en el Reino Unido e Irlanda, con el objetivo de planificar un tratamiento óptimo, registrar los resultados y proporcionar evidencia de los beneficios de la centralización. Este manuscrito presenta las actividades y los resultados de los primeros 2,5 años. MÉTODOS: Entre marzo de 2016 y diciembre de 2018, 155 pacientes con PM, remitidos a centros de cirugía oncológica peritoneal en Basingstoke, Good Hope Hospital en Birmingham, Christie Hospital en Manchester y Mater Misericordiae en Dublín, fueron discutidos en el National PM MDT a través de una videoconferencia. El MDT estaba compuesto por cirujanos, radiólogos, enfermeras especializadas y patólogos. Los pacientes fueron considerados para CRS e HIPEC si se determinaba que eran aptos para la cirugía y si las imágenes radiológicas sugerían que se podía lograr una citorreducción quirúrgica completa. Se analizó la morbilidad y mortalidad después de la cirugía. Se realizó un análisis de supervivencia tras la discusión en el MDT. RESULTADOS: En total, se discutieron 155 pacientes (tasa varón/mujer 0,96) con una edad media de 57 ± 17 años. Hasta el momento, 22 (14,2%) habían sido sometidos a CRS y HIPEC y la mediana de PCI en el grupo quirúrgico fue de 17,0. La citorreducción completa se logró en 19 (86,4%), las complicaciones de Clavien-Dindo grado I/II ocurrieron en 16/22, sin morbilidad de grado III/IV, ni mortalidad a los 30 días. La mediana de seguimiento fue de 15,0 meses y la supervivencia a los 2 años desde el momento de la revisión en el National PM MDT fue del 66,7%. CONCLUSIÓN: El National PM MDT centralizado fue eficaz en la selección de pacientes adecuados para CRS e HIPEC, presentando un buen resultado a partir de dicha selección.

Biological mesh is a safe and effective method of abdominal wall reconstruction in cytoreductive surgery for peritoneal malignancy.

BACKGROUND: Patients with peritoneal malignancy often have multiple laparotomies before referral for cytoreductive surgery (CRS). Some have substantial abdominal wall herniation and tumour infiltration of abdominal incisions. CRS involves complete macroscopic tumour removal and hyperthermic intraperitoneal chemotherapy (HIPEC). Abdominal wall reconstruction is problematic in these patients. The aim of this study was to establish immediate and long-term outcomes of abdominal wall reconstruction with biological mesh in a single centre. METHODS: A dedicated peritoneal malignancy database was searched for all patients who had biological mesh abdominal wall reconstruction between 2004 and 2015. Short- and long-term outcomes were reviewed. All patients had annual abdominal CT as routine peritoneal malignancy follow-up. RESULTS: Some 33 patients (22 women) with a mean age of 53·4 (range 19-82) years underwent abdominal wall reconstruction with biological mesh. The majority (23) had CRS for pseudomyxoma (19 low grade), six for colorectal peritoneal metastasis and four for appendiceal adenocarcinoma; 18 had undergone CRS and HIPEC previously. Twenty-five of the 33 patients had abdominal wall tumour involvement and eight had concurrent hernias. The mean duration of surgery was 486 (range 120-795) min and the mean mesh size used was 345 (50-654) cm2. Ten patients developed wound infections and four had a seroma. Two developed early enterocutaneous fistulas. Mean follow-up was 48 months. Five patients developed an incisional hernia. Four died from progressive malignancy. A further 15 patients had disease recurrence, but only one had isolated abdominal wall recurrence. CONCLUSION: Biological mesh was safe and effective for abdominal wall reconstruction in peritoneal malignancy. Postoperative wound infections were frequent but nevertheless incisional hernia rates were low with no instances of mesh-related bowel erosion or fistulation.

Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer.

AIM: Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. METHOD: A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. RESULTS: In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. CONCLUSION: Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.

The modified Glasgow prognosis score predicts for overall and disease-free survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma peritonei of appendiceal origin.

BACKGROUND: The modified Glasgow prognostic score (incorporating C-reactive protein and albumin) predicts survival in patients with gastro-intestinal tract cancer but has not been evaluated in patients with peritoneal malignancy. The aim was to evaluate the modified Glasgow score preoperatively in patients undergoing complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin. METHODS: Prospectively collected data from patients with PMP of appendiceal origin following CCRS and HIPEC between January 2007 and December 2011 were analysed. The mGPS was calculated from preoperative C-reactive protein and albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each mGPS score were calculated using the Kaplan-Meier model. In a separate analysis, a comparison was made between mGPS and Tumour Markers (TM). RESULTS: 260 patients were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and 19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9, and 54.4 months respectively. As mGPS increases, there is a reduction in long-term survival. There was no difference between mGPS and TM. CONCLUSION: Preoperative mGPS may be a cost effective prognostic tool for predicting OS and DFS in patients following complete CRS-HIPEC, and performs well compared to TM for predicting patients at high risk of recurrence.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1000 patients with perforated appendiceal epithelial tumours.

PURPOSE: To report early and long term outcomes following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 1000 patients with perforated appendiceal epithelial tumours, predominantly with pseudomyxoma peritonei (PMP). METHODS: Retrospective analysis of a prospective database of 1000 consecutive patients undergoing CRS and HIPEC for perforated appendiceal tumours between 1994 and 2014 in a UK National Peritoneal Malignancy unit. RESULTS: Overall 1000/1444 (69.2%) patients treated for peritoneal malignancy had appendiceal primary tumours. Of these 738/1000 (73.8%) underwent complete cytoreductive surgery (CCRS), 242 (24.2%) had maximal tumour debulking (MTD) and 20 (2%) had laparotomy and biopsies only. Treatment related 30-day mortality was 0.8% in CCRS and 1.7% in MTD group with major postoperative morbidity rates of 15.2% (CCRS) and 14.5% (MTD). Five- and 10-year overall survival was 87.4% and 70.3% in the 738 patients who had CCRS compared with 39.2% and 8.1% respectively in the MTD group. On multivariate analysis, significant predictors of reduced overall survival were male gender (p = 0.022), elevated CEA (p = 0.001), elevated CA125 (p = 0.001) and high tumour grade or adenocarcinoma (p = 0.001). CONCLUSIONS: Perforated epithelial appendiceal tumours are rare, though may be increasing in incidence and can present unexpectedly at elective or emergency abdominal surgery, often with PMP. CRS and HIPEC results in good long term outcomes in most patients.

A protocol for management of blood loss in surgical treatment of peritoneal malignancy by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND AIMS: The treatment of peritoneal malignancies with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be associated with massive surgical blood loss. Maintaining high fibrinogen levels throughout surgery may reduce blood loss in these patients. The primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate reduced surgical blood loss and hence red cell transfusions. A comparison was made with a cohort of patients treated with fresh frozen plasma (FFP) alone. The secondary aim was to measure the effect of both protocols on coagulation parameters and the incidence of arterial or venous thrombosis. METHOD: We used prospectively collected data from 201 patients who had complete CRS with HIPEC for peritoneal malignancy using different protocols during two discrete 12-month time periods. RESULTS: The new transfusion protocol led to a higher average fibrinogen level intra-operatively and post-operatively, with a significant reduction in average RBC, FFP and platelet transfusion intra-operatively per patient from 4·2 to 1·8 units, 6·2 to 0·2 units and 0·1 to 0 units, respectively. No significant difference in PT or APTT was seen between patients treated with the standard and new protocols. Venous thrombosis occurred in seven patients treated with the standard protocol and five with the new protocol. A single case of arterial thrombosis was seen in both groups. CONCLUSION: Patients treated with upfront TXA and cryoprecipitate during CRS required less RBC transfusion than those treated with the standard protocol of early FFP.

Procalcitonin levels predict infectious complications and response to treatment in patients undergoing cytoreductive surgery for peritoneal malignancy.

BACKGROUND: Cytoreductive-surgery for peritoneal-malignancy (PM) involves extensive intra-abdominal surgery and a massive post-operative systemic-inflammatory-response (SIRS). It is often challenging to differentiate SIRS that are solely surgery-associated from those of post-operative infections. White-Cell-Counts (WCC) and C-Reactive-Protein (CRP) are routinely used as markers for infection, but are non-specific and their elevation is often delayed in PM cases. Other markers need to be evaluated to assist early identification/prediction of post-operative infections. METHODOLOGY: Prospective evaluation of serum procalcitonin (PCT), CRP and WCC in 50 patients pre-operatively (Day0), and on post-operative days (POD) 1, 3 & 6, following cytoreductive-surgery with or without splenectomy. RESULTS: Day0 PCT, CRP and WCC values were within normal limits, but increasing physiologically in post-operative period without infection, with noticeable higher PCT in splenectomized patients. In our cohort post-operative infections were diagnosed in 14 patients, often within 48 h. There was a trend for faster rise in serum PCT on POD1 compared to CRP and WCC, and faster PCT decline following appropriate therapy on POD3 and POD6 when infected cases were clinically resolving while WCC and CRP continued to rise, particularly in non-spelenectomised patients. The AUC on POD1 was significantly higher for PCT (0.689) vs. WCC (0.476) and CRP (0.477) (p = 0.04). Sensitivity, specificity, positive-predictive-value and negative-predictive-values for PCT ranged between (57%-100%), (22%-74%), (33%-47%) & (81%-100%), for CRP (28%-78%), (5.5%-86%), (18%-44.4%) & (40%-75.5%) and for WCC (14%-26.5%), (65.5-80.5%), (22%-25%), (67%-70%) respectively. CONCLUSION: PCT, like WCC and CRP, needs to be interpreted with extreme cautions in the context of infections post-cytoreductive-surgery and should only be used in association with other clinical and investigational findings.

The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy.

AIM: The study determined the outcome of 1200 consecutive patients treated for peritoneal malignancy in one surgical unit over a 20-year period. METHOD: A retrospective analysis was conducted of a custom designed prospective database of patients undergoing surgery for peritoneal malignancy since 1994. Patient demographics, tumour type, extent of surgery and outcome were recorded. RESULTS: Between 1994 and January 2014 (when the 1200th case had undergone surgery) 2956 patients were referred with a diagnosis of peritoneal malignancy. Pseudomyxoma peritonei of appendiceal origin was the pathology in 956/1200 (79.7%) patients. Other aetiologies included colorectal peritoneal metastases [89/1200 (7.4%)], abdominal mesothelioma [65/1200 (5.4%)] and miscellaneous [90/1200 (7.5%)]. Overall 863/1200 (71.9%) had complete cytoreduction, 294 (24.5%) had maximal tumour debulking and 43 (3.6%) had laparotomy only. The proportion undergoing complete cytoreduction per quartile of 300 patients was 60.7%, 65.0%, 77.0% and 80.3%. Laparotomy and biopsy fell from 6.4% in the first quartile to 2.7%, 1.7% and 1.3% in subsequent quartiles. The 30-day mortality in the four quartiles was 3.0%, 1.0%, 0.7% and 0.7%. The 5-year survival was 84% in the 636 patients with appendix tumours who had complete cytoreduction, 76% in the 38 with abdominal mesothelioma and 44% in the 60 with colorectal peritoneal metastases. CONCLUSION: A centralized approach facilitated high volume experience in a single centre with an increase in the completeness of surgical excision rates and a reduction in mortality and morbidity over time.

Elevated tumour markers are normalized in most patients with pseudomyxoma peritonei 7 days after complete tumour removal.

AIM: Elevation of the preoperative tumour markers in pseudomyxoma peritonei (PMP) is common and is a risk factor for recurrence. There has, however, been no documentation of the effect of complete tumour removal on tumour markers levels after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to compare the tumour markers 7 days after surgery in patients with elevated preoperative levels. METHOD: This was an observational prospective study of patients with PMP of appendiceal origin treated in one of the UK National Referral Centres for this condition. Thirty patients [median age = 61 (range: 31-74) years; six men] with an elevated preoperative level of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and/or carbohydrate antigen 19-9 (CA19-9) underwent repeated estimation, 7 days after CRS and HIPEC for PMP. RESULTS: The median preoperative CEA level of 12 µg/l fell to 0.75 µg/l postoperatively (P < 0.0001), CA-125 fell from 45 to 31 kU/l (P = 0.183) and CA19-9 fell from 134 to 37 kU/l (P = 0.003). The CEA was raised in 22 (73%) of 30 patients preoperatively and in two (7%) of 30 patients 7 days after surgery (P < 0.0001). The corresponding data for CA-125 were 18 (60%) and 13 (43%) (P = 0.196) and for CA19-9 they were 24 (80%) and 16 (53%) (P = 0.028). CONCLUSION: This is the first documentation of a reduction or normalization of CEA 7 days after CRS, but not for CA19-9 or CA-125. This may indicate completeness of surgical resection and could aid selection for adjuvant therapy and predict prognosis. Long-term follow-up is, however, necessary to determine the significance of this observation.

Recurrence and outcome after complete tumour removal and hyperthermic intraperitoneal chemotherapy in 512 patients with pseudomyxoma peritonei from perforated appendiceal mucinous tumours.

BACKGROUND: Pseudomyxoma peritonei (PMP) usually originates from perforated mucinous appendiceal tumours and may present unexpectedly at surgery, or be suspected at cross sectional imaging. The optimal treatment involves macroscopic tumour removal by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The 10-year Kaplan-Meier predicted disease-free survival is 61%. Some patients with recurrence are amenable to further CRS and HIPEC. AIM: To evaluate the outcomes of re-do surgery in a large single centre series of reoperation for recurrence of peritoneal surface malignancy. METHOD: Retrospective analysis of prospective database of 752 patients undergoing CRS for perforated appendiceal tumours analysed. Routine follow up involved annual CT scans and serum tumour marker measurement. The survival and recurrence in the 512/752 (68.1%) who had complete cytoreduction between March 1994 and January 2012 was calculated by Kaplan-Meier univariate analysis. RESULTS: Overall 137/512 (26.4%) developed recurrence and of those 35/137 (25.5%) underwent repeat surgery. Complete tumour removal was again achieved in 20/35 (57.1%). There were no postoperative deaths and no significant difference in early postoperative complications and length of stay compared to primary CRS surgery. The 5-year survival in the 375 without recurrence, the 35 who had re-do surgery and the 102 who had recurrence with no surgery was 90.9%, 79.0% and 64.5% respectively. CONCLUSION: Approximately one in four patients develops recurrence after complete CRS and HIPEC for PMP of appendiceal origin. Selected patients can undergo salvage surgery with good outcomes.

Risk of definitive stoma after surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking.

INTRODUCTION: Complete cytoreductive surgery (CRS) can achieve cure or long-term survival in selected patients with peritoneal malignancy. In selected patients, due to extensive disease, complete tumour removal is impossible and optimal strategy may be maximal tumour debulking (MTD). We analysed the stoma related outcome in a series of patients undergoing surgery in a National Peritoneal Malignancy Referral Centre. METHODS: All patients who underwent CRS, with or without, intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) between 1994 and 2012 were included. Data was collected prospectively in an institutional database and analysed retrospectively. RESULTS: CRS was performed in 958 patients (female: 595, male: 363) of whom 781 (81.5%) had a primary appendix tumour, 63 (6.6%) had a colorectal primary, 47 (4.9%) peritoneal mesothelioma, 38 (4%) an ovarian tumour and 29 patients (3%) other tumours. Complete CRS was achieved in 72% (693/958). Overall 352/958 (37%) had a stoma, which was permanent in 165/958 (17.2%). The median time interval from CRS to reversal of stoma was 4.4 months (range: 1.4-13.8). Stomas were created in 113/265 (42.6%) at MTD (permanent: n = 105 (93%), temporary: n = 8 (7%)), and 239/693 (34.5%) at complete CRS (permanent: n = 60 (25%), temporary: n = 179 (75%)) (p = 0.020). All temporary stomas in the 168/693 (24.4%) of patients who had complete CRS were subsequently reversed. CONCLUSION: To achieve complete CRS for peritoneal malignancy a stoma is often required and in a proportion this will be permanent. Overall over one third had a stoma at surgery with almost half subsequently reversed.

Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone.

BACKGROUND: Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE). METHODS: An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel-Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I(2). The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone. RESULTS: Four studies (three case-control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72-4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17-7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE. CONCLUSIONS: Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.

Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal Pseudomyxoma Peritonei: Analysis of 519 patients.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable to further CRS. Clinical experience suggests a spectrum of disease which may correlate with tumour marker levels. The aim of this study was to analyse the influence of markers on recurrence and survival. METHODS: The details of all patients undergoing surgery for PMP of appendiceal origin at a national centre for peritoneal malignancy were recorded in a dedicated prospective database. The data on all patients who had CRS and HIPEC between March 1994 and January 2012 was analysed and recurrence and survival correlated with pre-operative levels of CEA, CA-125 and CA19-9. RESULTS: Overall, 519 (69%) of 752 consecutive patients, underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS) in the 131/519 patients who had normal preoperative tumour markers was 168 (128-207) and 125 (114-136) months respectively, significantly higher when compared with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42-88) and DFS of 55 (41-70) months respectively) (P = 0.002). CONCLUSIONS: Elevated tumour markers predict an increased risk of recurrence and reduced survival after complete CRS. This may reflect cell biology in low grade tumours and is an independent prognostic feature. Further analysis may help to select patients for post-operative chemotherapy, second look procedures or stratification of follow up.

The use of cardiac output monitoring to guide the administration of intravenous fluid during hyperthermic intraperitoneal chemotherapy.

AIM: The optimal strategy for intravenous (IV) fluid management during administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. In this prospective study we describe the use of a LiDCOrapid™ (LiDCO, Cambridge, UK) cardiac output monitor to guide IV fluid management during cytoreductive surgery (CRS) with HIPEC. The aim of this study was to determine whether cardiac output monitoring will allow close maintenance of physiological parameters during the HIPEC phase. METHOD: Twenty-five patients who underwent CRS combined with HIPEC were included in the study. Intra-operative IV fluid boluses were titrated using parameters measured by the LiDCOrapid™ monitor. Stroke volume variation was maintained below 10% with fluid boluses and mean arterial pressure was maintained within 20% of the baseline figure with vasopressors. RESULTS: There was no significant change in heart rate and cardiac output. The systemic vascular resistance dropped from an average of 966 dyn.s/cm-5 to 797 dyn s/cm(5) at 60 min during the HIPEC phase (P = 0.62) despite an increase in the dose of phenylepherine. The average total volume of fluid given was 748 ml in the first 30 min and 630 ml in the second 30 min with an average urine output of 307 and 445 ml, respectively. The change in lactate levels was not statistically or clinically significant. CONCLUSION: LiDCOrapid™ is an effective noninvasive tool for guiding fluid management in this population. It allows the anaesthesiologist to maintain tight control of essential physiological parameters during a phase of the procedure in which there is a risk of renal injury.

Peritoneal metastases from colorectal cancer: patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment modality for patients with pseudomyxoma peritonei. The majority of patients with pseudomyxoma who have complete tumour removal and HIPEC are cured. Over the last decade CRS for peritoneal metastasis of colorectal origin has emerged as an effective treatment strategy in carefully selected patients. Although convincing evidence is limited, available data shows promising results. The key to a successful outcome is appropriate selection of patients. In patients with extensive peritoneal disease, where complete cytoreduction is not achieved, surgical treatment may not be beneficial and might impair quality of life. In this paper we discuss the challenges of selecting patients with colorectal peritoneal metastases who are likely to benefit from CRS with HIPEC.

Alginate encapsulation of Begonia microshoots for short-term storage and distribution.

Synthetic seeds were formed from shoot tips of two in vitro grown Begonia cultivars using 3% sodium alginate in Murashige and Skoog medium (MS) salt solution as the gel matrix and 100 mM calcium chloride for complexation. Synthetic seed formation was achieved by releasing the sodium alginate/explant combination into 100 mM calcium chloride (CaCl2 ·H2O) solution for 30 or 45 min. Both control and encapsulated shoots were transferred into sterile Petri dishes and stored at 4°C or 22°C for 0, 2, 4, 6, or 8 weeks. Conversion of synthetic seeds into plantlets for both storage environments was assessed in MS medium or peat-based substrate. No significant difference was found between the 30 and 45 min CaCl2 ·H2O treatments or the two cultivars. Encapsulation of explants improved survival rate over time irrespective of the medium type or storage environment. Survival rates of 88, 53, 28, and 11% for encapsulated microshoots versus 73, 13, 0, and 0% for control explants were achieved in microshoots stored for 2, 4, 6, and 8 weeks, respectively. The best results were obtained when synthetic seeds were stored at 4°C and germinated on MS medium. Regenerated plantlets were successfully established in potting soil.