Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of... Show moreIntroduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome. Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting. Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795. Show less
Sluckin, T.C.; Hazen, S.M.J.A.; Horsthuis, K.; Beets-Tan, R.G.H.; Antonisse, I.E.; Berbee, M.; ... ; Dutch Snapshot Res Grp 2023
Background & purpose: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for ipsi-lateral local recurrences (LLR) in rectal cancer. This study examined... Show moreBackground & purpose: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for ipsi-lateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiotherapy practice in the Netherlands and associated LLR rates. Materials & methods: Patients with a primary tumor ≤8cm of the anorectal junction, cT3-4 stage and at least one internal iliac or obturator LLN with short-axis ≥5mm who received neoadjuvant (chemo)radiotherapy, were selected from a national, cross-sectional study of rectal cancer patients treated in the Netherlands in 2016. MR-images and radiotherapy treatment plans were reviewed regarding segmented LLNs as gross-tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiotherapy dose. Results: A total of 223 out of 3057 patients with at least one LLN ≥5mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received >95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared to inside (4.0% vs. 12.5%, p=.092) or when receiving <95% versus >95% of the planned radiotherapy dose (7.1% vs. 11.3%, p=.843), respectively. Two of seven patients who received a dose-escalation of 60Gy developed a LLR (4-year LLR rate 28.6%). Conclusion: This evaluation of routine radiotherapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further. Show less
Dassen, M.G.; Janssen, T.; Kusters, M.; Pos, F.; Kerkmeijer, L.G.W.; Heide, U.A. van der; Bijl, E. van der 2023
PurposeTo quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate... Show morePurposeTo quantify the difference in accuracy of adapt-to-position (ATP), adapt-to-rotation (ATR) and adapt-to-shape (ATS) workflows used in MRI-guided online adaptive radiotherapy for prostate carcinoma (PCa) by evaluating the margins required to accommodate intra-fraction motion of the clinical target volumes for prostate (CTVpros), prostate including seminal vesicles (CTVpros + sv) and gross tumor volume (GTV).Materials and methodsClinical delineations of the CTVpros, CTVpros + sv and GTV of 24 patients with intermediate- and high-risk PCa, treated using ATS on a 1.5 T MR-Linac, were used for analysis. Delineations were available pre- and during beam-on. To simulate ATP and ATR workflows, we automatically generated the structures associated with these workflows using rigid transformations from the planning-MRI to the daily online MRIs. Clinical GTVs were analyzed as ATR GTVs and only ATP GTVs were simulated. Planning target volumes (PTVs) were generated with isotropic margins ranging 0.0–5.0 mm. The volumetric overlap was calculated between these PTVs and their corresponding clinical delineation on the MRI acquired during beam-on and averaged over all treatment fractions.ResultsThe PTV margin required to cover > 95% of the CTVpros was equal (2.5 mm) for all workflows. For the CTVpros + sv, this margin increased to 5.0, 4.0 and 3.5 mm in the ATP, ATR and ATS workflow, respectively. GTV coverage improved from ATP to ATR for margins up to 4.0 mm.ConclusionATP, ATR and ATS workflows ensure equal coverage of the CTVpros for the current clinical margins. For the CTVpros + sv, ATS showed optimal performance. GTV coverage improves by additional adaptations to prostate rotations. Show less
Background. Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of... Show moreBackground. Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level.Methods. Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (=7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection.Results. Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874).Conclusion. Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research. Show less
Background: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter and location of lateral lymph nodes.Objective: To analyze lateral lymph node... Show moreBackground: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter and location of lateral lymph nodes.Objective: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training.Design: Retrospective population-based cross-sectional study. Settings: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals.Patients: 3057 patients underwent rectal cancer surgery in 2016: 1109 had cT3-4 tumor located ≤8cm from the anorectal junction of which 890 received neoadjuvant therapy. Interventions(s): NoneMain Outcome Measures: local recurrence and ipsi-lateral local recurrence rates. Results: Re-review identified 314 patients (35%) with visible lateral lymph nodes. 30 of these patients had either only long-stretched obturator (n=13) or external iliac (n=17) nodes and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n=284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7mm) lateral lymph nodes (n=122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%, p<.001) and lateral local recurrence (14.7%, 4.4%, 0%, p<.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (hazard ratio 1.8(1.1-2.8)) and enlarged lateral lymph nodes (hazard ratio 1.9(1.1-3.5)) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year LLR rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were associated with higher univariate 4-year distant metastasis rates (36.4% 24.4%, p=.021), but not in multivariable analysis (hazard ratio 1.3(0.9-1.8)), and did not worsen overall survival. Limitations: This study was limited by the retrospective design and total number of patients with lateral lymph nodes.Conclusions: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without prognostic impact of downsizing after neoadjuvant therapy. These results point towards the incorporation of primary lateral lymph node size into treatment planning. Show less
Schuetz, C.; Gerke, J.; Ege, M.; Walter, J.; Kusters, M.; Worth, A.; ... ; Primary Immune Deficiency Treat 2023
Patients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell... Show morePatients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% had autoimmunity, and 18% had granulomas pretransplant. These complications are frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3-42.9 years) from matched unrelated donors, matched sibling or matched family donors, or mismatched donors in 48%, 22%, and Show less
Kusters, M.; Rijst, R.M. van der; de Vetten, A.; Admiraal, W. 2023
Objectives The presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in... Show moreObjectives The presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in MRI reports is therefore essential. This study assessed whether LLNs were mentioned in primary MRI reports at a national level and investigated the concordance with standardised re-review. Methods This national, retrospective, cross-sectional cohort study included 1096 patients from 60 hospitals treated in 2016 for primary cT3-4 rectal cancer <= 8 cm from the anorectal junction. Abdominal radiologists re-reviewed all MR images following a 2-h training regarding LLNs. Results Re-review of MR images identified that 41.0% of enlarged (>= 7 mm) LLNs were not mentioned in primary MRI reports. A contradictory anatomical location was stated for 73.2% of all LLNs and a different size (>=/< 7 mm) for 41.7%. In total, 49.4% of all cases did not mention LLNs in primary MRI reports. Reporting LLNs was associated with stage (cT3N0 44.3%, T3N+/T4 52.8%, p = 0.013), cN stage (N0 44.1%, N1 48.6%, N2 59.5%, p < 0.001), hospital type (non-teaching 34.6%, teaching 52.2%, academic 53.2% p = 0.006) and annual rectal cancer resection volumes (low 34.8%, medium 47.7%, high 57.3% p < 0.001). For LLNs present according to original MRI reports (n = 226), 64.2% also mentioned a short-axis size, 52.7% an anatomical location and 25.2% whether it was deemed suspicious. Conclusions Almost half of the primary MRI reports for rectal cancer patients treated in the Netherlands in 2016 did not mention LLNs. A significant portion of enlarged LLNs identified during re-review were also not mentioned originally, with considerable discrepancies for location and size. These results imply insufficient awareness and indicate the need for templates, education and training. Show less
Objectives: Presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in MRI... Show moreObjectives: Presence and size of lateral lymph nodes (LLNs) are important factors influencing treatment decisions for rectal cancer. Awareness of the clinical relevance and describing LLNs in MRI-reports, is therefore essential. This study assessed whether LLNs were mentioned in primary MRI-reports at a national level and investigated the concordance with standardized re-review. Methods: This national, retrospective, cross-sectional cohort study included 1096 patients from 60 hospitals treated in 2016 for primary cT3-4 rectal cancer ≤8cm from the anorectal junction. Abdominal radiologists re-reviewed all MR-images after following a 2-hour training regarding LLNs. Results: Re-review of MR-images identified 41.0% of enlarged (≥7mm) LLNs were not mentioned in primary MRI-reports and a contradictory anatomical location was stated for 73.2% of all LLNs and a different size (≥/<7mm) for 41.7%. In total, 49.4% of cases did not mention LLNs in primary MRI-reports. Reporting LLNs was associated with stage (cT3N0 44.3%, T3N+/T4 52.8%, p=.013), cN-stage (N0 44.1%, N1 48.6%, N2 59.5%, p<.001), hospital type (non-teaching 34.6%, teaching 52.2%, academic 53.2% p=.006) and annual rectal cancer resection volumes (low 34.8%, medium 47.7%, high 57.3% p<.001). For LLNs identified during re-review (n=226), 64.2% original reports mentioned short-axis size, 52.7% location and 25.2% suspiciousness. Conclusions: Almost half of primary MRI-reports for rectal cancer patients treated in the Netherlands in 2016, did not mention LLNs. A significant portion of enlarged LLNs identified during re-review were also not mentioned originally, with considerable discrepancies for location and size. These results imply insufficient awareness and indicate the need for templates, education and training. Show less
Background: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision ... Show moreBackground: Standard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs.Methods: PubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed.Results: Seven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3-15%) compared to LLND- (11-27%; RR = 0.40, 95%CI [0.25-0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61-78% vs. 46-79% for LLND-; RR = 0.72, 95%CI [0.51-1.02], p = 0.143), and neither was five-year OS (range 69-91% vs. 72-80%; RR = 0.72, 95%CI [0.45-1.14], p = 0.163).Conclusion: In rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND. Show less
Introduction. Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT)... Show moreIntroduction. Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN.Patients and Methods. A multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of >= 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS).Results. Out of 115 patients, the majority was male (75%) and the median age was 64 years (range 26-85 years). Median pretreatment LLN short axis was 7 mm (range 5-28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5-6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS.Conclusion. The current study suggests that pre-treatment enlarged LLN that also harbor malignant features are predictive of a worse MMES. More studies will be required to further explore the role of malignant features in LLN. Show less
Background: In the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision ... Show moreBackground: In the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients. Methods: An international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (>5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group). Results: LLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND-(p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent sig-nificant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups. Conclusion: A LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Hazen, S.M.; Sluckin, T.; Beets, G.; Hompes, R.; Tanis, P.; Kusters, M.; Dutch Lateral Node Study Grp 2021
Purpose: The presence of lateral lymph nodes (LLNs) in patients with rectal cancer is notalways acknowledged by the multidisciplinary team or treated in a standardized manner,and (inter)national... Show morePurpose: The presence of lateral lymph nodes (LLNs) in patients with rectal cancer is notalways acknowledged by the multidisciplinary team or treated in a standardized manner,and (inter)national guidelines concerning this topic are lacking. This study aimed to evaluatecurrent practices regarding the assessment and treatment of LLNs in rectal cancer patientsbased on a survey among Dutch colorectal surgeons.Methods: An online survey was sent to members of the Dutch Association ofColoproctology. The survey consisted of 16 questions addressing their views on diagnosis,restaging, and treatment approaches for suspicious LLNs.Results: A total of 62 surgeons from 50 Dutch hospitals responded. For patients with a dis-tal cT3/T4 rectal tumor; lateral lymph node compartments were routinely discussed duringmultidisciplinary meetings in only nine hospitals (18%). When defining what makes an LLNsuspicious; the size threshold varied from >3 to >10 mm (median 7, SD 2), and MRI-basedmalignant features were mentioned by 29 surgeons (47%). Surgeons stated eight differenttreatment strategies as their designated treatment of suspicious LLNs. A total of 33 surgeons(53%) would add a radiotherapy boost to the neoadjuvant treatment. In cases of surgicalresection; 12 surgeons (19%) would remove the suspicious LLN by ‘node-picking’ and 44 sur-geons (71%) would perform a lateral lymph node dissection. The variation was not influ-enced by hospital type or surgeon’s experience.Conclusion: These results highlight the vast variation in the awareness, definition of suspi-cious LLNs in rectal cancer, and different treatment approaches. International guidelinesbased on further research are warranted. Show less
Western and Eastern practices have traditionally differed in their approach to treating lateral lymph nodes in rectal cancer. While Western clinicians have primarily favored neoadjuvant (chemo... Show moreWestern and Eastern practices have traditionally differed in their approach to treating lateral lymph nodes in rectal cancer. While Western clinicians have primarily favored neoadjuvant (chemo)radiotherapy to sterilize lateral compartments, Eastern physicians have often opted for the surgical removed of lymphatic tissue with a lateral lymph node dissection without neoadjuvant treatment. The literature suggests similar oncological outcomes for these two separate techniques, while tangible differences exist. The combination of these paradigms may be beneficial in reducing overall morbidity while sustaining low recurrence rates. This article considers traditional Eastern and Western perspectives, discusses nodal features important for predicting malignancy and attempts to stimulate international, multidisciplinary consensus and collaboration. Show less
Background The optimal timing of resection after decompression of left-sided obstructive colon cancer is unknown. Revised expert-based guideline recommendations have shifted from an interval of 5... Show moreBackground The optimal timing of resection after decompression of left-sided obstructive colon cancer is unknown. Revised expert-based guideline recommendations have shifted from an interval of 5-10 days to approximately 2 weeks following self-expandable metal stent (SEMS) placement, and recommendations after decompressing stoma are lacking. We aimed to evaluate the recommended bridging intervals after SEMS and explore the timing of resection after decompressing stoma.Methods This nationwide study included patients registered between 2009 and 2016 in the prospective, mandatory Dutch ColoRectal Audit. Additional data were collected through patient records in 75 hospitals. Only patients who underwent either SEMS placement or decompressing stoma as a bridge to surgery were selected. Technical SEMS failure and unsuccessful decompression within 48 hours were exclusion criteria.Results 510 patients were included (182 SEMS, 328 decompressing stoma). Median bridging interval was 23 days (interquartile range [IQR] 13-31) for SEMS and 36 days (IQR 22-65) for decompressing stoma. Following SEMS placement, no significant differences in post-resection complications, hospital stay, or laparoscopic resections were observed with resection after 11-17 days compared with 5-10 days. Of SEMS-related complications, 48% occurred in patients operated on beyond 17 days. Compared with resection within 14 days, an interval of 14-28 days following decompressing stoma resulted in significantly more laparoscopic resections, more primary anastomoses, and shorter hospital stays. No impact of bridging interval on mortality, disease-free survival, or overall survival was demonstrated.Conclusions Based on an overview of the data with balancing of surgical outcomes and timing of adverse events, a bridging interval of approximately 2 weeks seems appropriate after SEMS placement, while waiting 2-4 weeks after decompressing stoma further optimizes surgical conditions for laparoscopic resection with restoration of bowel continuity. Show less
Background Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal... Show moreBackground Carcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC. Methods Patients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose. Results Thirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients. Conclusions The optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019. Show less
