Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis

IntroductionThe aim of this study was to compare the outcome of patients with peritoneal metastasis (PM) of colorectal origin treated with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without perioperative systemic chemotherapy (PCT+/PCT-).Patients and methodsRetrospective analysis of 125 patients treated with complete CRS (R0/R1) and HIPEC for PM from colorectal origin in two Belgian academic centers between 2008 and 2017. Disease-free survival (DFS) and overall survival (OS) were assessed with regard to PCT. Statistical analyses were adjusted for non-balanced survival risk factors.ResultsThe PCT+ group (n = 67) received at least 5 cycles of PCT and the PCT-group (n = 56) did not receive PCT. The groups were well balanced for all prognostic factors except presentation of synchronous disease (more in PCT+). Survival analysis was adjusted to peritoneal cancer index and presentation of synchronous disease. After a median follow-up of 54±5-months, the 1, 3, 5-years OS in the PCT+ group were 98%, 59% and 35% compared to 97%, 77% and 56% in the PCT-group (HR = 1.46; 95% CI:0.87–2.47; p = 0.155). The 1,3 and 5 years DFS in the PCT+ group were 47%, 13% and 6% compared to 58%, 29% and 26% respectively in the PCT- (HR = 1.22; 95% CI:0.78–1.92; p = 0.376).ConclusionThis study does not show any clear benefit of PCT in carefully selected patients undergoing R0/R1 CRS and HIPEC for colorectal PM. The ongoing CAIRO6 trial randomizing CRS/HIPEC versus CRS/HIPEC and PCT will probably clarify the role of PCT in patients with resectable PM.     

Peroperative scoring systems for predicting the outcome of cytoreductive surgery in advanced-stage ovarian cancer – A systematic review

The extent of peritoneal metastases (PM) largely determines the possibility of complete or optimal cytoreductive surgery in advanced ovarian cancer. An objective scoring system to quantify the extent of PM can help clinicians to decide whether or not to embark on CRS. Therefore several scoring systems have been developed by different research teams and this review summarizes their performance in predicting a complete or optimal cytoreduction in patients with advanced ovarian cancer. A systematic search in the MEDLINE database revealed 19 articles that described a total of five main scoring systems to predict the completeness of CRS in patients with FIGO stage III-IV ovarian cancer based on the surgical exploration of the abdominal cavity; PCI, PIV, Eisenkop, Espada, and Kasper. The Peritoneal Cancer Index (PCI) and the Predictive Index Value (PIV) were mentioned most frequently and showed AUCs of 0.69–0.92 and 0.66–0.98, respectively. Due to the use of different cut-offs sensitivities and specificities greatly varied. Therefore with the current data, no scoring system could be identified as best. An objective measure of the extent of disease can be of great clinical use for identifying ovarian cancer patients for which a complete (or optimal) CRS is achievable, however due to local differences in treatment strategies and surgical policy a widely adopted objective scoring system with a standard cut-off value is not feasible. Nevertheless, objective scoring systems can play an important role to guide treatment decisions.     

Delayed genital necrosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C

IntroductionGenital necrosis (GN) is a rare complication of cytoreductive surgery with hyperthermic intraoperative chemotherapy (CRS/HIPEC) which can be confused with necrotizing fasciitis. We present an analysis of GN after CRS/HIPEC to define its natural history.MethodsWe identified patients with GN after CRS/HIPEC at two peritoneal surface malignancy institutions. Patient demographic, surgical, and postoperative data were extracted from prospective databases.ResultsOf 1597 CRS/HIPECs performed, 13 patients (0.8%) had GN. The median age was 57 years (IQR: 49–64) and 77% (n = 10) were male. Mitomycin-C was the perfusion agent in all cases of GN (100%). The median time to GN onset after CRS/HIPEC was 64 days (IQR: 60–108) and 2 (15%) patients were receiving systemic chemotherapy at the time of GN onset. Symptoms included severe pain (100%), edema (100%), labial or scrotal skin ulceration (92%), signs of infection (39%), and fever (15%). Seven (54%) patients had thrombocytosis >400 110⁹/L, whereas coagulation tests were within normal reference range in 100% cases. All patients initially underwent conservative treatment, with antibiotic therapy administered in 62% (n = 8). Surgical debridement was performed in 9 (70%) cases with median time after GN onset of 57 (IQR: 8–180).ConclusionGN is a debilitating complication after CRS/HIPEC with delayed onset and a protracted clinical course. Optimal treatment results could be achieved with initial conservative management until complete lesion demarcation followed by surgical debridement. The pathophysiology of GN is unclear, and we call for other researchers attention to better understand the complication and prevention.     

The value of lymph node ultrasound and whole body 18F-FDG PET/CT in stage IIB/C melanoma patients prior to SLNB

BackgroundStage IIB/IIC (8th AJCC) melanoma patients are known to have high-risk primary tumors, however they follow the same routine to sentinel lymph node biopsy (SLNB) as more low risk tumors. Guidelines are not conclusive regarding the use of preoperative imaging for these patients. The aim of this pilot study was to assess the value of ultrasound (US) and ¹⁸F-FDG PET/CT prior to lymphoscintigraphy (LSG) and SLNB for stage IIB/C melanoma patients.MethodsFrom 2019-04 till 2020–01, all stage IIB/C melanoma patients underwent US of the regional lymph nodes and whole body ¹⁸F-FDG PET/CT before their planned LSG and SLNB. Suspected metastases were confirmed with fine needle aspiration (FNA), prior to surgery.ResultsIn total 23 patients were screened: six had metastases detected by imaging, two by US, one by ¹⁸F-FDG PET/CT and three were detected by both imaging modalities. All metastases were nodal and therefore treatment was altered to lymph node dissection and all but one also received adjuvant therapy. Eight (47%) of the 17 patients without macroscopic disease, still had a positive SN. Sensitivity, specificity and false negative rate for US and ¹⁸F-FDG PET/CT were 36%, 89%, 64% and 29%, 100% and 71%, respectively.ConclusionPreoperative negative imaging does not exclude the presence of SN metastases, therefore SLNB cannot be foregone. However, US detected metastases in 22% of patients, altering their treatment, which suggests it is effective in the work-up of stage IIB/C melanoma. Staging with ¹⁸F-FDG PET/CT is not of added value prior to LSG and SLNB and should therefore not be used.     

Risk of contralateral ovarian cancer in patients undergoing conservative surgery for ovarian cancer

BackgroundAmong patients with ovarian cancer (OC), the risk of contralateral OC remains controversial and few studies have focused on the occurrence of contralateral OC after conservative surgery.MethodsBasing on the Surveillance, Epidemiology, and End Results (SEER) database registered between 2000 and 2018, Logistic and Cox regressions were established to test the risk factors of contralateral OC. Kaplan-Meier mothed was used to calculate the cumulative risk curve for contralateral OC and compared using log-rank test. Furthermore, the frequency of contralateral OC and standardized incidence ratios (SIRs) were evaluated.Results18807 patients were included, 69 patients developed contralateral OC. Logistic and Cox regressions showed patients diagnosed >50 years had lower risk of contralateral OC (Odds ratio [OR]:0.42, 95% confidence interval [CI]: 0.24–0.73; Hazard ratios [HR]:0.44, 95%CI:0.24-0.77). Patients with radical surgery had lower contralateral OC risk (OR:0.20, 95%CI: 0.11–0.36; HR: 0.17, 95%CI: 0.09–0.30). The SIR for contralateral OC was high in all patients (SIR: 2.37, 95%CI: 1.85–3.00) and highest if patients diagnosed <50 years with conservative surgery (SIR: 27.33, 95%CI: 19.86–36.69). However, the SIR for contralateral OC was low in patients diagnosed ≥50 years with radical surgery (SIR: 0.54, 95%CI: 0.26–1.00). No statistically significant SIRs were observed in patients diagnosed ≥50 years with conservative surgery and patients diagnosed <50 years with radical surgery.ConclusionsOur study provided some information for clinicians to assess the risk of contralateral OC and suggested young patients should not undergo hysterectomy to prevent contralateral OC. Moreover, clinical surveillance cannot be relaxed.     

Systemic inflammatory markers for the detection of infectious complications and safe discharge after cytoreductive surgery and HIPEC

IntroductionCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in patients with ovarian peritoneal carcinomatosis may be associated with a high postoperative morbidity. An early discrimination of postoperative complications is crucial for both improving clinical outcomes and proposing a safe discharge.Material and methodsIn a cohort of 122 patients with advanced ovarian cancer (FIGO III-IV), we analyzed the diagnostic performance of three systemic inflammatory markers (C-reactive protein, white blood cell count and systemic immune-inflammation index) between the 5th to 8th postoperative days to prediction postoperative infectious complications. An optimal cut-off value was established in order to discriminate between the group of patients who developed infectious complications or not during the postoperative period.ResultsThe median peritoneal carcinomatosis index (PCI) was 15. The overall infectious morbidity was 25.4% (31 patients out of 122), of which, 32% (10 patients out of 31) had suffered severe postoperative complications (Dindo-Clavien III-IV). The most accurate results for detecting infectious complications were obtained by using C-reactive protein, which presented an excellent diagnostic performance, especially on the 7th and 8th postoperative days (AUC = 0,857 and 0,920; respectively).ConclusionsThese results support that it is safe to discharge patients with C-reactive protein concentrations lower than 88 mg/L and 130 mg/L, on the 7th and 8th postoperative days, respectively.     

Days alive and out of hospital after surgical treatment of epithelial ovarian cancer: A Danish nationwide cohort study

ObjectiveDays alive and out of hospital (DAOH) is a validated outcome measure in perioperative trials integrating information on primary hospitalization, readmissions, and mortality. It is negatively associated with advanced age. However, DAOH has not been described for surgical treatment of epithelial ovarian cancer (EOC), primarily diagnosed in older patients.MethodsWe conducted a Danish nationwide cohort study including patients undergoing debulking surgery for EOC from 2013 to 2018. DAOH was explored for 30 (DAOH30), 90 (DAOH90), and 180 (DAOH180) postoperative days in younger (<70 years) and older (≥70 years) patients with advanced-stage disease stratified by surgical modality (primary (PDS) or interval debulking surgery (IDS)). We examined the associations between patient- and surgical outcomes and low or high DAOH30.ResultsOverall, 1168 patients had stage IIIC-IV disease and underwent debulking surgery. DAOH30 was 22 days [interquartile range (IQR): 18, 25] and 23 days [IQR: 18, 25] for younger and older patients treated with PDS, respectively. For IDS, DAOH30 was 25 days [IQR: 22, 26] for younger and 25 days[IQR: 21, 26] for older patients. We found no significant differences between age cohorts regarding DAOH30, DAOH90, and DAOH180. Low DAOH30 was associated with poor performance status, PDS, extensive surgery, and long duration of surgery in adjusted analysis.ConclusionsDAOH did not differ significantly between age cohorts. Surgical rather than patient-related factors were associated with low DAOH30. Our results likely reflect a high selection of fit older patients for surgery, reducing the patient-related differences between younger and older patients receiving surgical treatment.     

Comorbidities,timing of treatments,and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study

IntroductionFor stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established.Materials and methodsWe analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use.ResultsOverall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P < 0.001). Chemotherapy timing did not vary (P = 0.250) between high and low comorbidity cases. Electively-operated cases with low comorbidities received surgery more promptly than high comorbidity cases. Risks of death and relapse were lower for elective cases given surgery after four weeks than cases given surgery within a week. High comorbidities were always independently associated with poorer outcomes. Chemotherapy use increased over time.ConclusionsOur data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation.     

Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer

PurposeThe aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status.MethodsSeventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0–1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately.ResultsThe rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005).ConclusionsNarrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.     

Metastatic pattern discriminates survival benefit of primary surgery for de novo stage IV breast cancer: A real-world observational study

IntroductionRole of surgery in the management of de novo stage IV breast cancer (BC) remains controversial. We aimed to determine the survival benefit of primary surgery on the basis of metastatic pattern.Materials and methodsA retrospective cohort study based on the SEER database was conducted to identify patients with de novo stage IV BC diagnosed between 2010 and 2015. Patients were divided into surgery and non-surgery group, and propensity score weighting was used to balance clinicopathologic factors between groups.ResultsOf 8142 de novo stage IV BC patients, 1891 (23%) cases were managed with surgery and 6251 (77%) cases were managed without surgery. There were 3821 all-cause deaths and 3291 BC specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 54.5%, compared to 47.7% (P < 0.001) for the non-surgery group. The magnitude of the survival difference with surgery was significantly correlated with metastatic patterns (P_interaction<0.05). Significant survival improvements in surgery group compared with non-surgery group were observed in patients with bone-only metastasis (adjusted HR = 0.83, P < 0.05) or multiple metastases with bone involved (adjusted HR = 0.76, P < 0.05), whereas survival inferiority of surgery was found for patients with multiple visceral organs-only metastases (adjusted HR = 2.08, P < 0.05).ConclusionThe survival benefit offered by surgery for de novo stage IV BC varies by metastatic patterns. Decisions for primary surgery of de novo stage IV BC patients should be tailored according to metastatic pattern.     

Evaluation of dual-energy CT derived radiomics signatures in predicting outcomes in patients with advanced gastric cancer after neoadjuvant chemotherapy

BackgroundTo investigate the prognostic value of dual-energy CT (DECT) based radiomics to predict disease-free survival (DFS) and overall survival (OS) for patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC).MethodsFrom January 2014 to December 2018, a total of 156 AGC patients were enrolled and randomly allocated into a training cohort and a testing cohort at a ratio of 2:1. Volume of interest of primary tumor was delineated on eight image series. Four feature sets derived from pre-NAC and delta radiomics were generated for each survival arm. Random survival forest was used for generating the optimal radiomics signature (RS). Statistical metrics for model evaluation included Harrell's concordance index (C-index) and the average cumulative/dynamic AUC throughout follow-up. A clinical model and a combined Rad-clinical model were built for comparison.ResultsThe pre-IU (derived from iodine uptake images before NAC) RS performed best for DFS and OS in the testing cohort (C-indices, 0.784 and 0.698; the average cumulative/dynamic AUCs, 0.80 and 0.77). When compared with the clinical model, the radiomics model had significantly higher C-index to predict DFS in the testing cohort (0.784 vs. 0.635, p < 0.001), but no statistical difference was found for OS (0.698 vs. 0.680, p = 0.473). The combined Rad-clinical models showed improved performance in the testing cohort, with C-indices of 0.810 and 0.710 for DFS and OS, respectively.ConclusionDECT-derived radiomics serves as a promising non-invasive biomarker to predict survival for AGC patients after NAC, providing an opportunity for transforming proper treatment.     

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

IntroductionPatients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices.Materials and methodsPatients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured.ResultsBefore treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression).ConclusionThese data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC).MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL.ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98).ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.     

"When and how are peritoneal metastases of colo-rectal origin treatable"

Peritoneal metastasis (PM) of colorectal cancer (CRC) origin can be treated and cured. This article presents a practical guide for CRC surgeons facing a patient with PM and presents the different options of treatment at expert centers on peritoneal surface malignancies.The unexpected finding of PM could be overwhelming, especially during an emergency CRC surgery. Clear indications on managing these situations call for clarification to avoid any negative impact on the oncologic outcome of patients with CRC.All patients with PM of CRC origin must be evaluated by a tumor board or multidisciplinary team specialized in the management of peritoneal surface malignancies since currently there are available options of treatment for patients with resectable peritoneal disease, unresectable peritoneal disease, and even patients with synchronous liver metastases (LM) could benefit from a multimodal approach.     

A nationwide study on cancer recurrences,second primary tumours,distant metastases and survival after treatment for primary head and neck cancer in the Netherlands

IntroductionThere is no consensus on the optimal duration of post-treatment follow-up after head and neck cancer (HNC). To generate site-specific input for follow-up guidelines, this study describes the incidence and timing of manifestations of disease during five years of follow-up.MethodsAll patients diagnosed with HNC in the Netherlands in 2015 were selected from the Netherlands Cancer Registry. The follow-up events local recurrence (LR), regional recurrence (RR), second primary tumour (SPT), distant metastasis (DM) and death were studied per follow-up-year. The cumulative incidence of these events was calculated using competing risk analyses, with LR, RR and SPT of the head and neck (SPHNC) as events and SPT outside the head-neck (SPOHN), DM and death as competing events. Analyses were performed for oral cavity-, oropharynx-, larynx- and hypopharynx squamous cell carcinoma (SCC), and all HNC patients.ResultsThe 1-, 1.5-, and 2-year cumulative incidence of an event (LR, RR, SPHNC) were 10% (95%CI 8–13), 12% (95%CI 10–15), and 13% (95%CI 10–16) for oral cavity SCC; 6% (95%CI 4–9), 10% (95%CI 7–14), and 11% (95%CI 8–15) for oropharynx SCC; 7% (95%CI 5–10), 11% (95%CI 9–15), and 13% (95%CI 10–16) for larynx SCC and 11% (95%CI 6–19), 19% (95%CI 12–27), and 19% (95%CI 12–27) for hypopharynx SCC.ConclusionsOne year of follow-up for oral cavity SCC, and 1.5 years for oropharynx-, larynx-, and hypopharynx SCC suffices for the goal of detecting disease manifestations after treatment. More research into other aspects of follow-up care should be performed to determine the optimal follow-up regimen.     

The role of surgery for locally recurrent and second recurrent rectal cancer with metastatic disease

BackgroundThe role of surgery for locally recurrent rectal cancer (LRRC) with resectable distant metastases or second LRRC remains unclear. This study aimed to clarify the influence of synchronous distant metastases (SDMs), a history of distant metastasis resection (HDMR), and a second LRRC on the outcome.MethodsThe long-term outcomes of 70 surgically treated patients with LRRC between 2006 and 2018 were compared by SDM (n = 10), HDMR (n = 17), and second LRRC (n = 7).ResultsAmong the 10 patients with SDM, 4 patients underwent simultaneous resection, whereas the other 6 underwent staged resection with distant first approach. Recurrence developed in 9 patients, of which 2 patients with liver re-resection achieved long-term survival without cancer. The patients with and without SDM had equivalent 5-year overall survival rate (40.5% vs. 53.3%, p = 0.519); however, patients with SDM had a worse 3-year recurrence-free survival rate than those without SDM (10.0% vs. 37.5%, p = 0.031). Multivariate analysis showed that primary non-sphincter-preserving surgery, second LRRC, and R1 resection were independent risk factors for overall survival. Similarly, primary non-sphincter-preserving surgery, second LRRC, SDM, and R1 resection were risk factors for recurrence-free survival.ConclusionsPatients with SDM might still be suitable to undergo salvage surgery and achieve favourable overall survival. Distant metastasectomy should be performed first, followed by a sufficient interval to avoid unnecessary LRRC resection in uncurable patients. An HDMR should not be taken into consideration when making surgical plans. Surgical indication of second LRRC should be strict, especially in referred patients.     

Current practices and barriers to referral for cytoreductive surgery and HIPEC among colorectal surgeons: A binational survey

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained traction for the management of peritoneal metastases. The number of specialist units globally offering CRS/HIPEC is increasing. The aim of this survey was to assess current practices and barriers to referral for CRS/HIPEC among colorectal surgeons in Australia and New Zealand (ANZ).Materials and methodsAn online questionnaire was emailed to members of the Colorectal Surgical Society of Australia and New Zealand (CSSANZ). The survey contained 3 sections: namely; demographics, referral patterns and clinical scenarios. Questions on referral patterns included number of peritoneal metastases patients seen per year and referred to a CRS/HIPEC unit, awareness of such a unit and distance from principle place of practice. Different pathologies referred were also explored, as well as investigations performed. Barriers to referral were also surveyed.ResultsThe response rate was 28% (83/296). Twenty-five percent received CRS training. Most surgeons (95%) were aware of a CRS/HIPEC unit and had referred to one previously. Thirty-nine percent would refer all patients. Provision of good service and/or relationship with CRS/HIPEC specialist were the main reasons for referring to the nearest unit, followed by accessibility. Major factors preventing referral included extent of peritoneal disease (48%), patient characteristics and comorbidities (44%) and lack of evidence (20%). The most common pathologies referred included colorectal and appendiceal peritoneal metastases and pseudomyxoma peritonei.ConclusionColorectal specialist awareness of CRS/HIPEC units and accessibility is high. Strategies to improve referring physician/surgeon knowledge on patient selection and indications for CRS/HIPEC should be investigated and instituted to ensure all appropriate patients are referred to specialist units for discussion of suitability.