Major differences in follow-up practice of patients with colorectal cancer; results of a national survey in the Netherlands.

BACKGROUND: The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined. METHODS: Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods. RESULTS: A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99-100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent. CONCLUSIONS: Dutch colorectal surgeons' adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC.

Systematic review and meta-analysis for laparoscopic versus open colon surgery with or without an ERAS programme.

BACKGROUND: In recent years, conventional colorectal resection and its aftercare have increasingly become replaced by laparoscopic surgery and enhanced recovery after surgery (ERAS) pathways, respectively. OBJECTIVE: To ascertain whether combining laparoscopy and ERAS have additional value within colorectal surgery. METHODS: A systematic review with meta-analysis was performed with two primary research questions; does laparoscopy offer an advantage when all patients receive ERAS perioperative care and does ERAS offer advantages in a laparoscopically operated patient population. All randomised and controlled clinical trials were identified using MEDLINE, EMBASE and Cochrane databases. RESULTS: Primary search resulted in 319 hits. After inclusion criteria were applied, three RCTs and six CCTs were included in the meta-analysis. For laparoscopically operated patients with/without ERAS, no differences in morbidity were found and postoperative hospital stay favoured ERAS (MD -2.34 [-3.77, -0.91], Z = 3.20, p = 0.001). When comparing laparoscopy and open surgery within ERAS, major morbidity was significantly reduced in the laparoscopic group (OR 0.42 [0.26, 0.66], Z = 3.73, p = 0.006). Other outcome parameters showed no differences. Quality of included studies was considered moderate to poor overall with small sample sizes. CONCLUSION: When laparoscopy and ERAS are combined, major morbidity and hospital stay are reduced. The reduction in morbidity seems to be due to laparoscopy rather than ERAS, so laparoscopy by itself offers independent advantages beyond ERAS care. Quality of included studies was moderate to poor, so conclusions should be regarded with some reservations.

Transanal endoscopic microsurgery following treatment with imatinib : a case report of a patient with a rectal gastrointestinal stromal tumor.

BACKGROUND: Gastrointestinal stromal tumors (GIST) of the rectum are a challenge for the colorectal surgeon. In case of a locally advanced rectal GIST, an extended or multivisceral resection with significant morbidity and -mortality is often necessary. Literature is lacking on the combined modality of transanal endoscopisc microsurgery (TEM) following imatinib for these patients. METHODS: We describe a combined approach for a locally advanced GIST of the rectum with preoperative imatinib -treatment and subsequent local excision using the TEM procedure. RESULTS: After six months of treatment with imatinib the TEM procedure was successfully performed with a radical -resection of the remnant tumor. Twenty-four months after surgery this patient has no evidence of disease. CONCLUSIONS: A TEM procedure following treatment with imatinib may safely be performed in selected patients with a locally advanced GIST.

Transanal endoscopic microsurgery approach for rectal stump resection as an alternative to transperitoneal stump resection.

BACKGROUND: Transperitoneal rectal stump resection is a complicated procedure with risk of inadvertent bowel, vascular and nerve injury. This study analysed the feasibility and safety of the use of transanal endoscopic microsurgery (TEM) to excise rectal stumps that would otherwise require a combined transabdominal and perineal approach. METHODS: Rectal stump resection was performed by a transanal approach using TEM. Stumps were removed by complete rectal wall resection and intersphincteric resection of the anus, leaving the mesorectum in place. RESULTS: The study included nine patients with a rectal stump ranging in length from 8 to 20 cm after previous surgery for inflammatory bowel disease (6), Lynch syndrome (1), collagenous colitis (1) or anastomotic leakage (1). The median duration of operation was 161 (range 107-239) min. The median postoperative length of hospital stay was 5 (range 2-71) days. One patient required an additional small-incision laparotomy to remove a stump extending up to the promontory and another developed a postoperative abscess. There were no perioperative complications. CONCLUSION: TEM appeared to be a useful and safe approach for close rectal dissection and removal of a rectal stump while avoiding an abdominal approach for pelvic dissection.

Consensus review of best practice of transanal irrigation in adults.

STUDY DESIGN: Review article. OBJECTIVES: To provide a consensus expert review of the treatment modality for transanal irrigation (TAI). METHODS: A consensus group of specialists from a range of nations and disciplines who have experience in prescribing and monitoring patients using TAI worked together assimilating both the emerging literature and rapidly accruing clinical expertise. Consensus was reached by a round table discussion process, with individual members leading the article write-up in the sections where they had particular expertise. RESULTS: Detailed trouble-shooting tips and an algorithm of care to assist professionals with patient selection, management and follow-up was developed. CONCLUSION: This expert review provides a practical adjunct to training for the emerging therapeutic area of TAI. Careful patient selection, directly supervised training and sustained follow-up are key to optimise outcomes with the technique. Adopting a tailored, stepped approach to care is important in the heterogeneous patient groups to whom TAI may be applied. SPONSORSHIP: The review was financially supported by Coloplast A/S.

Prehabilitation to improve postoperative outcomes in patients with peritoneal carcinomatosis undergoing hyperthermic intraperitoneal chemotherapy (HIPEC): A scoping review.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) leads to increased survival rates in patients with peritoneal carcinomatosis, but is associated with considerable morbidity and mortality rates. Prehabilitation, a process to optimize a patient's preoperative functional capacity, has a positive impact on recovery after colorectal surgery. The impact of prehabilitation in patients undergoing HIPEC is scarcely investigated. This scoping review and narrative synthesis aims to summarize and evaluate what is currently reported about the effect of prehabilitation on postoperative outcomes after HIPEC. METHODS: A literature search of studies reporting on the effect of prehabilitation on outcomes after HIPEC was performed (August 2020). Study characteristics, patient demographics, composition of prehabilitation programs, and reported outcomes used to quantify the effect of prehabilitation were recorded. RESULTS: The literature search did not yield any studies on the effect of prehabilitation programs on outcomes after HIPEC. As an alternative, studies identifying modifiable risk factors for poor postoperative outcomes after HIPEC that can be targeted by prehabilitation were reviewed to evaluate starting points for prehabilitation. Fourteen studies identify the following preoperative factors: poor nutritional status, poor performance status, low health related quality of life and an history of smoking. CONCLUSION: No research has been published on the effect of prehabilitation prior to HIPEC. This review demonstrates that preoperative modifiable risk factors for outcomes in patients undergoing HIPEC are multifactorial. A multimodal prehabilitation program prior to HIPEC, including nutritional support, psychical exercise, psychological support and smoking cessation, might therefore be a promising approach to improve postoperative outcomes.

Wear behavior of a microhybrid composite vs. a nanocomposite in the treatment of severe tooth wear patients: A 5-year clinical study.

OBJECTIVE: This study aimed to compare the wear behavior of a microhybrid composite vs. a nanocomposite in patients suffering from severe tooth wear. METHODS: A convenience sample of 16 severe tooth wear patients from the Radboud Tooth Wear Project was included. Eight of them were treated with a microhybrid composite (Clearfil APX, Kuraray) and the other eight with a nanocomposite (Filtek Supreme XTE, 3M). The Direct Shaping by Occlusion (DSO) technique was used for all patients. Clinical records were collected after 1 month (baseline) as well as 1, 3 and 5 years post-treatment. The maximum height loss at specific areas per tooth was measured with Geomagic Qualify software. Intra-observer reliability was tested with paired t-tests, while multilevel logistic regression analyses were used to compare odds ratios (OR) of "large amount of wear". RESULTS: Intra-observer reliability tests confirmed that two repeated measurements agreed well (p > 0.136). For anterior mandibular teeth, Filtek Supreme showed significantly less wear than Clearfil APX; in maxillary anterior teeth, Clearfil APX showed significantly less wear (OR material = 0.28, OR jaw position = 0.079, p < 0.001). For premolar and molar teeth, Filtek Supreme showed less wear in bearing cusps, whereas Clearfil APX showed less wear in non-bearing cusps (premolar: OR material = 0.42, OR bearing condition = 0.18, p = 0.001; molar: OR material = 0.50, OR bearing condition = 0.14, p < 0.001). SIGNIFICANCE: Nanocomposite restorations showed significantly less wear at bearing cusps, whereas microhybrid composite restorations showed less wear at non-bearing cusps and anterior maxillary teeth.

[Carcinoma of the colon with bladder invasion; what is the role of preoperative chemotherapy?] / Coloncarcinoom met doorgroei in de blaas.

Preoperative chemotherapy followed by surgery was applied in three patients, aged 68 years (male), 48 years (female), and 80 years (male) with locally advanced cancer of the colon with bladder invasion. Achieving a resection with free margins (R0) is essential in colon-cancer surgery, but the role of preoperative chemotherapy in colon cancer remains unknown. When a tumour is presumed to be unresectable, guidelines recommend discussing the case and possibly referring the patient to an oncological expertise centre, where each patient will be individually assessed for the most suitable preoperative treatment and surgery during a multidisciplinary tumour board meeting. All three patients showed that preoperative chemotherapy led to down-staging and reduction of the tumour size, although removal of the bladder was still necessary in one patient. All patients underwent a complete resection, which resulted in long-term disease-free and overall survival.

Development and implementation of a remote follow-up plan for colorectal cancer patients.

Colorectal cancer is a common disease and patient follow-up can overwhelm outpatient services. Cancer patients are followed to provide (psychological) support, and to identify and treat disease recurrence and complications. This article describes our thoughts on, and first experience with the development and implementation of an alternative, remote follow-up plan for colorectal cancer patients. Within remote follow-up, patients have access to test results, and are supported with self-management information. They have access to telemedicine applications such as video-consultation, text messaging, and telephone services to contact their physician and nurse practitioner. Routine outpatient clinical visits are abandoned. Currently, 66 patients are being followed remotely. Application of telemedicine within cancer follow-up has several advantages. Patients do not have to travel back and forth, sparing time, costs and efforts. Second, telemedicine applications increase patient empowerment. If applied safely, remote follow-up may become a viable alternative to clinical follow-up.

Effect of intraperitoneal chemotherapy concentration on morbidity and survival.

BACKGROUND: Selected patients with colorectal peritoneal metastases are treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The concentration of intraperitoneal chemotherapy reflects the administered dose and perfusate volume. The aim of this study was to calculate intraperitoneal chemotherapy concentration during HIPEC and see whether this was related to clinical outcomes. METHODS: An observational multicentre study included consecutive patients with colorectal peritoneal metastases who were treated with CRS-HIPEC between 2010 and 2018 at three Dutch centres. Data were retrieved from prospectively developed databases. Chemotherapy dose and total circulating volumes of carrier solution were used to calculate chemotherapy concentrations. Postoperative complications, disease-free and overall survival were correlated with intraoperative chemotherapy concentrations. Univariable and multivariable logistic regression, Cox regression and survival analyses were performed. RESULTS: Of 320 patients, 220 received intraperitoneal mitomycin C (MMC) and 100 received oxaliplatin. Median perfusate volume for HIPEC was 5·0 (range 0·7-10·0) litres. Median intraperitoneal chemotherapy concentration was 13·3 (range 7·0-76·0) mg/l for MMC and 156·0 (91·9-377·6) mg/l in patients treated with oxaliplatin. Grade III or higher complications occurred in 75 patients (23·4 per cent). Median overall survival was 36·9 (i.q.r. 19·5-62·9) months. Intraperitoneal chemotherapy concentrations were not associated with postoperative complications or survival. CONCLUSION: CRS-HIPEC was performed with a wide variation in intraperitoneal chemotherapy concentrations that were not associated with complications or survival.

ANTECEDENTES: Ciertos pacientes seleccionados con metástasis peritoneales de cáncer colorrectal (peritoneal metastases, PM) se tratan con cirugía citorreductora (cytoreductive surgery, CRS) y quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC). La concentración de quimioterapia intraperitoneal refleja la dosis administrada y el volumen perfundido. El objetivo de este estudio fue calcular la concentración de quimioterapia intraperitoneal durante HIPEC y evaluar si ello se relacionaba con los resultados clínicos. MÉTODOS: Estudio observacional multicéntrico en el que se incluyeron pacientes consecutivos con PM de cáncer colorrectal que fueron tratados con CRS-HIPEC entre 2010 y 2018 en tres centros holandeses. Se obtuvieron los datos a partir de bases de datos mantenidas de forma prospectiva. La dosis de quimioterapia y los volúmenes circulantes totales de solución de perfusión se usaron para calcular las concentraciones de quimioterapia. Las complicaciones postoperatorias y las supervivencias libre de enfermedad y global se correlacionaron con las concentraciones de quimioterapia intraoperatoria. Se realizaron regresiones logísticas univariable y multivariable, regresión de Cox y análisis de supervivencia. RESULTADOS: De 320 pacientes, 220 recibieron mitomicina C intraperitoneal (MMC) y 100 oxaliplatino (OXA). El volumen medio de perfusión para HIPEC fue 5,0 L (rango 0,7-10,0). La mediana de concentración intraperitoneal del agente quimioterápico fue de 13,3 mg/L (rango 7,0-76,0) para MMC y 156,0 mg/L (rango 91,9 - 377,6) en pacientes tratados con OXA. Las complicaciones de grado 3 o mayores ocurrieron en 23,4% (n = 75). La mediana de supervivencia global fue de 36,9 meses (rango intercuartílico 19,5-62,9). Las concentraciones de quimioterapia intraperitoneal no se asociaron con las complicaciones postoperatorias ni con la supervivencia. CONCLUSIÓN: La CRS-HIPEC se realizó con una amplia variación en las concentraciones de quimioterapia intraperitoneal que no se asociaron con las complicaciones ni con la supervivencia.

[Severe vaginal discharge following rectal surgery]. / Ernstige fluor vaginalis na rectumresectie.

BACKGROUND: Almost 50% of women who have had rectal surgery subsequently develop vaginal discharge. Due to the recurrent and unexpected nature of this heavy discharge, they often experience it as very distressing. Many of these women undergo extensive diagnostic tests that are mainly focused on identifying fistula formation. If no fistula is found, in most cases no other cause for severe vaginal discharge can be demonstrated. CASE DESCRIPTION: In our practice, we saw three patients (49-, 54- and 74-years-old, respectively) with similar severe vaginal discharge after rectal surgery and in whom no explanation for the vaginal discharge could be found. For this reason we conducted a literature search into this condition. CONCLUSION: Anatomical changes appear to be responsible for heavy vaginal discharge following rectal surgery. Changes in pelvic floor muscles and compression of the distal part of the vagina may lead to pooling of fluid in the proximal part of the vagina, resulting in severe discharge. Symptomatic treatment may reduce the symptoms.

Prudent application of radiofrequency ablation in resectable colorectal liver metastasis.

Radiofrequency ablation (RFA) for liver metastasis of colorectal (H-CRC) origin is a well-documented technique in surgically unresectable disease. Overall recurrence figures appear inferior to resection but are based on a selection of patients with unresectable disease, often due to multiple localisations of extensive disease. Lesion based recurrence is probably more appropriate to predict results of RFA in surgically resectable H-CRC and figures may be good enough to consider RFA an alternative treatment in high risk patients.

Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer.

INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and neoadjuvant treatments have improved outcome for patients with rectal cancer. Patients with distal rectal cancer undergoing an abdominoperineal excision seem to do worse compared to those treated with sphinctersparing techniques. The aim of this study was to evaluate the quality of care for patients undergoing an abdominoperineal excision for distal rectal cancer during the last 15 years. MATERIALS AND METHODS: All patients with rectal cancer, who underwent an abdominoperineal excision between December 1996 and December 2010 in 5 Dutch hospitals were analysed. Patients were divided into three cohorts; 1996-2001, 2001-2005 and 2006-2010. All data was extracted from medical records. RESULTS: 477 patients were identified. There was no significant difference in sex, age, BMI, prior pelvic surgery and ASA stages between the cohorts. MRI became a standard tool in the work-up, the use increased from 4.5% in the first, to 95.1% in the last cohort (p < 0.0001). Neoadjuvant treatment shifted from predominantly none (64.9% in cohort 1) to short course radiotherapy (66.7% in cohort 2) and chemoradiation therapy (55.7% in cohort 3). There was a trend towards a decreased circumferential resection margin involvement in the cohorts (18.8%, 16.7% and 11.4%; p = 0.142). Accidental bowel perforations have significantly decreased from 28.6%, and 21.7% to 9.2% in cohort 3 (p < 0.0001). CONCLUSION: Significant improvements in work-up, neoadjuvant and surgical treatment have been made for patients with low rectal cancer, undergoing an abdominoperineal excision. These improvements result in improved short term outcome.

Cancer surgery: the last 25 years.

Surgery is, and always has been, the main treatment modality of solid tumours. For a long period, it consisted of a number of surgical procedures dictated by basic oncologic principles, most of which are still adhered to. Over the last few decades, increased understanding of the disease, new or improved diagnostic facilities, novel and perfected adjuvant treatments, improved surgical techniques and daring challenges to established dogmas have all contributed to the development of surgical oncology. The heritage from the past came under close scrutiny, and the fruits of basic and clinical science were added to an ever expanding body of knowledge. It is impossible to review all developments in surgical oncology of the last 25 years in one comprehensive paper. Therefore we have restricted ourselves to those items that appear most representative for the changes that have taken place, and those diseases that have the greatest numerical impact.

Immunology and immunotherapy of human cancer: present concepts and clinical developments.

Immunotherapy of cancer is entering into a new phase of active investigation both at the pre-clinical and clinical level. This is due to the exciting developments in basic immunology and tumour biology that have allowed a tremendous increase in our understanding of mechanisms of interactions between the immune system and tumour cells. This review briefly summarizes the state of the art in basic tumour immunology before discussing the clinical applications of the new concepts in the clinical setting. Clinical approaches are diverse but can now be based on strong scientific rationales. The analysis of the available clinical results suggests that, despite some disappointments, there is room for optimism that both active immunotherapy (vaccination) and adoptive immunotherapy may soon become part of the therapeutic arsenal to combat cancer in a more efficient way.

An HLA class I peptide-binding assay based on competition for binding to class I molecules on intact human B cells. Identification of conserved HIV-1 polymerase peptides binding to HLA-A*0301.

A peptide-binding assay employing the HLA class I molecules on intact human B cells is described. The peptide antigens are stripped from the HLA class I molecules by mild acid treatment, after which the cells are incubated with a FL-labeled reference peptide together with different concentrations of the peptide of interest. The effectiveness by which the latter peptide competes for binding to the HLA class I molecules is assayed by measuring the amount of HLA-bound FL-labeled reference peptide with FACscan analysis. The assay is easy to perform because there is no need to purify HLA class I molecules, or to transfect cells with HLA class I molecules, and no radioactive label is used. Moreover, large panels of HLA-typed human B-cell lines are available as tools for peptide binding to a vast array of HLA molecules. The binding assay was optimized and validated with peptides of known binding capacity to either HLA-A*0201 or HLA-A*0301. The kinetics of peptide binding in this assay were shown to be comparable to that in assays employing soluble HLA class I molecules. Application of the assay in the search for potential HLA-A*0301 restricted CTL epitopes, derived from HIV-1 polymerase, resulted in the identification of five high-affinity binding peptides.

Tumour immunotherapy: the adjuvant treatment of the 21st century?

In the course of a century, tumour immunology has revealed a picture of a very complex immune system involving the recognition and eradication of malignancies. Many tumours evade the immune system, and understanding of tumour escape mechanisms is the key to a successful immunotherapy for cancer. A wide array of tumour immunotherapy modalities have been developed, many of which have reached the phase of clinical trials, with some satisfactory results. Based on the available clinical, data and the techniques available for further improvement, we analyse the prospects for the different treatment modalities, and predict an important role for tumour immunotherapy in the near future.

Laparoscopic adhesiolysis for chronic abdominal pain: an objective assessment.

BACKGROUND AND PURPOSE: Postoperative adhesions frequently occur and can account for various symptoms, including chronic abdominal pain. Conventional adhesiolysis by laparotomy results in an unacceptably high rate of recurrence. A minimally invasive procedure (laparoscopic adhesiolysis) might improve the outcome by inflicting less surgical trauma, but well-documented reports focused on laparoscopic adhesiolysis for chronic abdominal pain are lacking. PATIENTS AND METHODS: Twelve consecutive patients with chronic abdominal pain caused by adhesions who were treated by laparoscopic adhesiolysis were assessed preoperatively and during a 1-year follow-up period applying validated scoring systems: McGill and SLC-90 tests to evaluate personalities and MOS SF-36 and GIQLI questionnaires for the quality of life assessments. RESULTS: No psychological influences were identified. Only two patients experienced a lasting improvement in quality of life, and five patients had more or less stable complaints. Five patients required laparotomy within a year after laparoscopic adhesiolysis. CONCLUSIONS: Laparoscopic adhesiolysis has yet not passed the stage of clinical trial and requires objective evaluation, including detailed information on recurrence and de novo adhesions in correlation with clinical outcome.