Clinical studies regarding colorectal cancer (CRC) have suggested differences in metastatic patterns between mucinous adenocarcinoma (MC), signet-ring cell carcinoma (SRCC) and the more common ...adenocarcinoma (AC). The current study systematically evaluates metastatic patterns of different histological subtypes in CRC patients and analyzes metastatic disease upon primary tumor localization.
A nationwide retrospective review of pathological records of 5817 patients diagnosed with CRC who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA). To substantiate clinical relevance, metastatic patterns were compared with the prospective randomized multicenter Total Mesorectal Excision (TME) trial, which investigated efficacy of preoperative radiotherapy in rectal cancer patients.
In the autopsy study, 1675 patients had metastatic disease. MC and SRCC patients more frequently had metastatic disease (33.9% and 61.2% versus 27.6%; P < 0.0001) and had metastases at multiple sites more often compared with AC patients (58.6% and 70.7% versus 49.9%; P = 0.001). AC predominantly metastasized to the liver, and MC and SRCC more frequently had peritoneal metastases. Metastatic patterns were also related to the primary tumor site, with a high rate of abdominal metastases in colon cancer patients, whereas rectal cancer patients more often had metastases at extra-abdominal sites. Results from the TME trial confirmed findings in rectal cancer patients from the autopsy study.
There are profound differences in metastatic patterns between histological subtypes and the localization of the primary tumor in CRC. Findings from this study should encourage to take these factors into account for follow-up strategies and future studies.
Background
This prospective multicentre study was performed to quantify the number of patients with minimal residual disease (ypT0–1) after neoadjuvant chemoradiotherapy and transanal endoscopic ...microsurgery (TEM) for rectal cancer.
Methods
Patients with clinically staged T1–3 N0 distal rectal cancer were treated with long‐course chemoradiotherapy. Clinical response was evaluated 6–8 weeks later and TEM performed. Total mesorectal excision was advocated in patients with residual disease (ypT2 or more).
Results
The clinical stage was cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy‐related complications of at least grade 3 occurred in 23 of 55 patients, with two deaths from toxicity, and two patients did not have TEM or major surgery. Among 47 patients who had TEM, ypT0–1 disease was found in 30, ypT0 N1 in one, ypT2 in 15 and ypT3 in one. Local recurrence developed in three of the nine patients with ypT2 tumours who declined further surgery. Postoperative complications grade I–IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion) surgery. After a median follow‐up of 17 months, four local recurrences had developed overall, three in patients with ypT2 and one with ypT1 disease.
Conclusion
TEM after chemoradiotherapy enabled organ preservation in one‐half of the patients with rectal cancer.
Organ preservation feasible
Background
Total mesorectal excision (TME) gives excellent oncological results in rectal cancer treatment, but patients may experience functional problems. A novel approach to performing TME is by ...single‐port transanal minimally invasive surgery. This systematic review evaluated the functional outcomes and quality of life after transanal and laparoscopic
TME.
Methods
A comprehensive search in PubMed, the Cochrane Library, Embase and the trial registers was conducted in May 2019. PRISMA guidelines were used. Data for meta‐analysis were pooled using a random‐effects model.
Results
A total of 11 660 studies were identified, from which 14 studies and six conference s involving 846 patients (599 transanal TME, 247 laparoscopic TME) were included. A substantial number of patients experienced functional problems consistent with low anterior resection syndrome (LARS). Meta‐analysis found no significant difference in major LARS between the two approaches (risk ratio 1·13, 95 per cent c.i. 0·94 to 1·35; P = 0·18). However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment.
Conclusion
No differences in function were observed between transanal and laparoscopic
TME.
Antecedentes
La escisión total del mesorrecto (total mesorectal excision, TME) proporciona excelentes resultados oncológicos en el tratamiento del cáncer de recto, pero los pacientes pueden presentar trastornos funcionales. Un abordaje novedoso para realizar la TME es mediante cirugía transanal mínimamente invasiva de puerto único. En esta revisión sistemática se evaluaron los resultados funcionales y la calidad de vida después de TME transanal (TaTME) y TME laparoscópica (LapTME).
Métodos
En mayo de 2019 se realizó una búsqueda exhaustiva en las bases de datos de Pubmed, Biblioteca Cochrane, EMBASE y en los registros de ensayos clínicos. Se utilizaron las guías PRISMA. Los datos para el metaanálisis se agruparon utilizando un modelo de efectos aleatorios.
Resultados
Se identificaron un total de 11.660 estudios, de los cuales se incluyeron 14 estudios y 6 resúmenes de congresos con 846 pacientes (599 TaTME/247 LapTME). Un número sustancial de pacientes presentó trastornos funcionales consistentes con el síndrome de resección anterior baja (low anterior resection syndrome, LARS). El metaanálisis no encontró diferencias significativas en los porcentajes de LARS grave entre los dos abordajes (razón de oportunidades, odds ratio, OR 1,13; i.c. del 95% 0,94‐1,35; P = 0,18). Sin embargo, los estudios globalmente presentaron una gran heterogeneidad, así como una deficiente información sobre la evaluación funcional basal.
Conclusión
No se observaron diferencias en la función entre TaTME y LapTME.
A novel surgical technique for total mesorectal excision (TME) is single‐port transanal minimally invasive surgery. This systematic review aimed to evaluate the functional outcomes and quality of life after transanal total mesorectal excision (TaTME) and compare them with those of laparoscopic TME (LapTME). No differences between TaTME and LapTME were seen in terms of impaired functioning and reduced quality of life after rectal cancer surgery. However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment.
Comparable function
Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the ...outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy.
The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up.
If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival.
The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, ...but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC.
This population-based study involved 27 251 unselected patients diagnosed with colorectal carcinoma between 1990 and 2010 and recorded in a prospective pathology-based registry. Kaplan–Meier analysis and log-rank testing were used to estimate survival. Cox proportional hazard model was used to calculate multivariate hazard ratios for death.
MC was found in 12.3% (N = 3052) of colorectal tumors with a different distribution compared with NMC, with 24.4% located in the rectum and 54.3% in the proximal colon (versus 38.0% and 30.6%), P < 0.0001. NMC was more often classified as stage I disease than MC (20.5% versus 10.9%), P < 0.0001. After adjustments for covariates, MC was associated with a higher risk of death only when located in the rectum hazard ratio 1.22; 95% confidence interval (CI) 1.11–1.34. Multivariate regression analysis showed a similar survival after adjuvant chemotherapy for stage III MC and NMC patients.
The poor prognosis for MC is only present in rectal cancer. In the adjuvant setting, there is no difference in the efficacy of chemotherapy between MC and NMC; therefore, current adjuvant treatment recommendations should not take histology into account.
The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of ...cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14
DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.
Seroma is the most common complication following breast cancer surgery, with reported incidence up to 90%. Seroma causes patient discomfort, is associated with surgical site infections (SSI), often ...requires treatment and increases healthcare consumption. The quilting suture technique, in which the skin flaps are sutured to the pectoralis muscle, leads to a significant reduction of seroma with a decrease in the number of aspirations and surgical site infections. However, implementation is lagging due to unknown side effects, increase in operation time and cost effectiveness. Main objective of this study is to assess the impact of large scale implementation of the quilting suture technique in patients undergoing mastectomy and/or axillary lymph node dissection (ALND).
The QUILT study is a stepped wedge design study performed among nine teaching hospitals in the Netherlands. The study consists of nine steps, with each step one hospital will implement the quilting suture technique. Allocation of the order of implementation will be randomization-based. Primary outcome is 'textbook outcome', i.e.no wound complications, no re-admission, re-operation or unscheduled visit to the outpatient clinic and no increased use of postoperative analgesics. A total of 113 patients is required based on a sample size calculation. Secondary outcomes are shoulder function, cosmetic outcome, satisfaction with thoracic wall and health care consumption. Follow-up lasts for 6 months.
This will be one of the first multicentre prospective studies in which quilting without postoperative wound drain is compared with conventional wound closure. We hypothesize that quilting is a simple technique to increase textbook outcome, enhance patient comfort and reduce health care consumption.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Treatment of rectal cancer is shifting toward organ preservation aiming to reduce surgery-related morbidity. Short-term outcomes of organ-preserving strategies are promising, but ...long-term outcomes are scarce in the literature. OBJECTIVE: To explore long-term oncological outcomes and health-related quality of life (HRQL) in patients with cT1-3N0M0 rectal cancer who underwent neoadjuvant chemoradiotherapy (CRT) followed by transanal endoscopic microsurgery (TEM). DESIGN, SETTING, AND PARTICIPANTS: In this multicenter phase II feasibility study, patients with cT1-3N0M0 rectal cancer admitted to referral centers for rectal cancer throughout the Netherlands between February 2011 and September 2012 were prospectively included. These patients were to be treated with neoadjuvant CRT followed by TEM in case of good response. An intensive follow-up scheme was used to detect local recurrences and/or distant metastases. Data from validated HRQL questionnaires and low anterior resection syndrome questionnaires were collected. Data were analyzed from February 2011 to April 2017. MAIN OUTCOMES AND MEASURES: The primary study outcome of the study was the number of ypT0-1 specimens by performing TEM. Secondary outcome parameters were locoregional recurrences and HRQL. RESULTS: Of the 55 included patients, 30 (55%) were male, and the mean (SD) age was 64 (39-82) years. Patients were followed up for a median (interquartile range) period of 53 (39-57) months. Two patients (4%) died during CRT, 1 (2%) stopped CRT, and 1 (2%) was lost to follow-up. Following CRT, 47 patients (85%) underwent TEM, of whom 35 (74%) were successfully treated with local excision alone. Total mesorectal excision was performed in 16 patients (4 with inadequate responses, 8 with completion after TEM, and 4 with salvage for local recurrence). The actuarial 5-year local recurrence rate was 7.7%, with 5-year disease-free and overall survival rates of 81.6% and 82.8%, respectively. Health-related quality of life during follow-up was equal to baseline, with improved emotional well-being in patients treated with local excision (mean score at baseline, 72.0; 95% CI, 67.1-80.1; mean score at follow-up, 86.9; 95% CI, 79.2-94.7; P = .001). Major, minor, and no low anterior resection syndrome was experienced in 50%, 28%, and 22%, respectively, of patients with successful organ preservation. CONCLUSIONS AND RELEVANCE: In early-stage rectal cancer (cT1-3N0M0), CRT enables organ preservation with additional TEM surgery in approximately two-thirds of patients with good long-term oncological outcome and HRQL. This multimodality treatment triggers a certain degree of bowel dysfunction, and one-third of patients still undergo radical surgery and are overtreated by CRT.
Surgery for complex primary and metastatic colorectal cancer (CRC), such as liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), in academic settings has led to improved survival ...but is associated with complications up to 75%. Prehabilitation has been shown to prevent complications in non-academic hospitals. This pilot study aimed to determine the feasibility and potential efficacy of a multimodal prehabilitation program in patients undergoing surgery in an academic hospital for complex primary and metastatic CRC.
All patients awaiting complex colorectal surgery, liver resection, or HIPEC from July 2019 until January 2020 were considered potentially eligible. Feasibility was measured by accrual rate, completion rate, adherence to the program, satisfaction, and safety. To determine potential efficacy, postoperative outcomes were compared with a historical control group.
Sixteen out of twenty-five eligible patients (64%) commenced prehabilitation, and fourteen patients fully completed the intervention (88%). The adherence rate was 69%, as 11 patients completed >80% of prescribed supervised trainings. No adverse events occurred, and all patients expressed satisfaction with the program. The complication rate was significantly lower in the prehabilitation group (37.5%) than the control group (70.2%,
= 0.020). There was no difference in the type of complications.
This pilot study illustrates that multimodal prehabilitation is feasible in the majority of patients undergoing complex colorectal cancer, liver resection, and HIPEC in an academic setting.
Distant metastatic disease is frequently observed in inflammatory breast cancer (IBC), with a poor prognosis as a consequence. The aim of this study was to analyze the association of hormone receptor ...(HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS).
For patients with stage IV IBC, diagnosed in the Netherlands between 2005 and 2016, tumors were classified into four breast cancer subtypes: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Patient, tumor, and treatment characteristics and sites of metastases were compared. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. Association between subtype and OS was assessed in multivariable models using logistic regression.
In total, 744 eligible patients were included: 340 (45.7%) tumors were HR+/HER2-, 148 (19.9%) HR-/HER2+, 131 (17.6%) HR+/HER2+, and 125 (16.8%) HR-/HER2-. Bone was the most common metastatic site in all subtypes. A significant predominance of bone metastases was found in HR+/HER2- IBC (71.5%), and liver and lung metastases in the HR-/HER2+ (41.2%) and HR-/HER2- (40.8%) subtypes, respectively. In multivariable analysis, the HR-/HER2- subtype was associated with significantly worse OS as compared to the other subtypes.
Breast cancer subtypes in stage IV IBC are associated with distinct patterns of metastatic spread and display notable differences in OS. The use of breast cancer subtypes can guide a more patient-tailored staging directed to metastatic site and extend of disease.
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